Ttt of diabetes (bnf may 2012)

61 BNF

March 2011

British National Formulary

6 Endocrine system

6.1 Drugs used in diabetes 418

6.1.1 Insulins 419

6.1.1.1 Short-acting insulins 422

6.1.1.2 Intermediate- and long-actinginsulins 423

6.1.1.3 Hypodermic equipment 426

6.1.2 Antidiabetic drugs 427

6.1.2.1 Sulfonylureas 427

6.1.2.2 Biguanides 429

6.1.2.3 Other antidiabetic drugs 430

6.1.3 Diabetic ketoacidosis 435

6.1.4 Treatment of hypoglycaemia 435

6.1.5 Treatment of diabetic nephropa-thy and neuropathy 436

6.1.6 Diagnostic and monitoringdevices for diabetes mellitus 437

6.2 Thyroid and antithyroid drugs 439

6.2.1 Thyroid hormones 439

6.2.2 Antithyroid drugs 440

6.3 Corticosteroids 442

6.3.1 Replacement therapy 442

6.3.2 Glucocorticoid therapy 442

6.4 Sex hormones 449

6.4.1 Female sex hormones 449

6.4.1.1 Oestrogens and HRT 449

6.4.1.2 Progestogens 456

6.4.2 Male sex hormones and antago-nists 458

6.4.3 Anabolic steroids 461

6.5 Hypothalamic and pituitary hor-mones and anti-oestrogens 461

6.5.1 Hypothalamic and anterior pitui-tary hormones and anti-oestro-gens 461

6.5.2 Posterior pituitary hormones andantagonists 466

6.6 Drugs affecting bone metab-olism 469

6.6.1 Calcitonin and parathyroidhormone 470

6.6.2 Bisphosphonates and otherdrugs affecting bone metabolism 471

6.7 Other endocrine drugs 477

6.7.1 Bromocriptine and otherdopaminergic drugs 477

6.7.2 Drugs affecting gonadotrophins 479

6.7.3 Metyrapone and trilostane 482

6.7.4 Somatomedins 483

This chapter also includes advice on the drug man-agement of the following:

Adrenal suppression during illness, trauma orsurgery, p. 444Serious infections in patients taking corticoster-oids, p. 444Osteoporosis, p. 469Breast pain (mastalgia), p. 482

For hormonal contraception, see section 7.3.

6.1 Drugs used in diabetes

6.1.1 Insulins

6.1.2 Antidiabetic drugs

6.1.3 Diabetic ketoacidosis

6.1.4 Treatment of hypoglycaemia

6.1.5 Treatment of diabetic nephropathyand neuropathy

6.1.6 Diagnostic and monitoring devices fordiabetes mellitus

Diabetes mellitus occurs because of a lack of insulin orresistance to its action. It is diagnosed by measuringfasting or random blood-glucose concentration (andoccasionally by oral glucose tolerance test). Althoughthere are many subtypes, the two principal classes ofdiabetes are type 1 diabetes and type 2 diabetes.

Type 1 diabetes, (formerly referred to as insulin-depen-dent diabetes mellitus (IDDM)), occurs as a result of adeficiency of insulin following autoimmune destructionof pancreatic beta cells. Patients with type 1 diabetesrequire administration of insulin.

Type 2 diabetes, (formerly referred to as non-insulin-dependent diabetes (NIDDM)), is due to reduced secre-tion of insulin or to peripheral resistance to the action ofinsulin or to a combination of both. Although patientsmay be controlled on diet alone, many also require oralantidiabetic drugs or insulin (or both) to maintain satis-factory control. In overweight individuals, type 2 dia-betes may be prevented by losing weight and increasingphysical activity; use of the anti-obesity drug orlistat(section 4.5.1) may be considered in obese patients.

Treatment of diabetes Treatment of all forms ofdiabetes should be aimed at alleviating symptoms andminimising the risk of long-term complications (seebelow); tight control of diabetes is essential.

Diabetes is a strong risk factor for cardiovascular dis-ease (section 2.12). Other risk factors for cardiovasculardisease such as smoking (section 4.10.2), hypertension(section 2.5), obesity (section 4.5), and hyperlipidaemia

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(section 2.12) should be addressed. Cardiovascular riskin patients with diabetes can be further reduced by theuse of an ACE inhibitor (section 2.5.5.1), low-doseaspirin (section 2.9) and a lipid-regulating drug (section2.12).

Prevention of diabetic complications Optimalglycaemic control in both type 1 diabetes and type 2diabetes reduces, in the long term, the risk of micro-vascular complications including retinopathy, develop-ment of proteinuria and to some extent neuropathy.However, a temporary deterioration in established dia-betic retinopathy may occur when normalising blood-glucose concentration. For reference to the use of anACE inhibitor or an angiotensin-II receptor antagonist inthe management of diabetic nephropathy, see section6.1.5.

A measure of the total glycosylated (or glycated) hae-moglobin (HbA1) or a specific fraction (HbA1c) providesa good indication of glycaemic control over the previous2–3 months. Overall it is ideal to aim for an HbA1c

(glycosylated haemoglobin) concentration of 48–59 mmol/mol (6.5–7.5%) or less (reference range 20–42 mmol/mol or 4–6%) but this cannot always beachieved and for those using insulin there is a signifi-cantly increased risk of disabling hypoglycaemia; inthose at risk of arterial disease, the aim should be tomaintain the HbA1c concentration at 48 mmol/mol(6.5%) or less. HbA1c should be measured every 3–6months.

Measurement of HbA1c

HbA1c values currently expressed as a percentage,are aligned to the assay used in the Diabetes Con-trol and Complications Trial (DCCT). A new stan-dard, specific for HbA1c, has been created by theInternational Federation of Clinical Chemistry andLaboratory Medicine (IFCC), which expressesHbA1c values in mmol of glycosylated haemoglobinper mol of haemoglobin. UK laboratories nowexpress results in both IFCC-standardised units(mmol/mol) and DCCT-aligned units (%). From 1June 2011, results will only be reported in IFCC-standardised units.

Equivalent values

IFCC-HbA1c (mmol/mol) DCCT-HbA1c (%)

42 6.0

48 6.5

53 7.0

59 7.5

64 8.0

75 9.0

Laboratory measurement of serum-fructosamine con-centration is technically simpler and cheaper than themeasurement of HbA1c and can be used to assesscontrol over short periods of time, particularly whenHbA1c monitoring is invalid (e.g. disturbed erythrocyteturnover or abnormal haemoglobin type).

Tight control of blood pressure in hypertensive patientswith type 2 diabetes reduces mortality and protectsvisual acuity (by reducing considerably the risks ofmaculopathy and retinal photocoagulation) (see alsosection 2.5).

Driving Drivers with diabetes are required to notify theDriver and Vehicle Licensing Agency (DVLA) of theircondition if they are treated with insulin or if they aretreated with oral antidiabetic drugs and also have com-plications. Detailed guidance on eligibility to drive isavailable from the DVLA (www.dvla.gov.uk/medical.aspx). Driving is not permitted when hypogly-caemic awareness is impaired or frequent hypoglycae-mic episodes occur.

Drivers need to be particularly careful to avoid hypo-glycaemia (see also above) and should be warned of theproblems. Drivers treated with insulin should normallycheck their blood-glucose concentration before drivingand, on long journeys, at 2-hour intervals; these pre-cautions may also be necessary for drivers taking oralantidiabetic drugs who are at particular risk of hypo-glycaemia. Drivers treated with insulin should ensurethat a supply of sugar is always available in the vehicleand they should avoid driving if their meal is delayed. Ifhypoglycaemia occurs, or warning signs develop, thedriver should:

. stop the vehicle in a safe place;

. switch off the ignition;

. eat or drink a suitable source of sugar;

. wait until recovery is complete before continuingjourney; recovery may take 15 minutes or longerand should preferably be confirmed by checkingblood-glucose concentration.

6.1.1 Insulins

6.1.1.1 Short-acting insulins

6.1.1.2 Intermediate- and long-acting insulins

6.1.1.3 Hypodermic equipment

Insulin plays a key role in the regulation of carbohy-drate, fat, and protein metabolism. It is a polypeptidehormone of complex structure. There are differences inthe amino-acid sequence of animal insulins, humaninsulins and the human insulin analogues. Insulin maybe extracted from pork pancreas and purified by crystal-lisation; it may also be extracted from beef pancreas, butbeef insulins are now rarely used. Human sequenceinsulin may be produced semisynthetically by enzy-matic modification of porcine insulin (emp) or bio-synthetically by recombinant DNA technology usingbacteria (crb, prb) or yeast (pyr).

All insulin preparations are to a greater or lesser extentimmunogenic in man but immunological resistance toinsulin action is uncommon. Preparations of humansequence insulin should theoretically be less immuno-genic, but no real advantage has been shown in trials.

Insulin is inactivated by gastro-intestinal enzymes, andmust therefore be given by injection; the subcutaneousroute is ideal in most circumstances. Insulin is usuallyinjected into the upper arms, thighs, buttocks, or abdo-men; absorption from a limb site may be increased if thelimb is used in strenuous exercise after the injection.Generally subcutaneous insulin injections cause fewproblems; lipodystrophy may occur but can be mini-mised by using different injection sites in rotation. Localallergic reactions are rare.

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Insulin is needed by all patients with ketoacidosis, and itis likely to be needed by most patients with:

. rapid onset of symptoms;

. substantial loss of weight;

. weakness;

. ketonuria;

. a first-degree relative who has type 1 diabetes.

Insulin is required by almost all children with diabetes. Itis also needed for type 2 diabetes when other methodshave failed to achieve good control, and temporarily inthe presence of intercurrent illness or peri-operatively.Pregnant women with type 2 diabetes may be treatedwith insulin when diet alone fails. For advice on use oforal antidiabetic drugs in the management of diabetes inpregnancy, see section 6.1.2.

NHS Diabetes guidanceSafe and Effective Use of Insulin inHospitalised Patients (March 2010)Available at www.diabetes.nhs.uk

Management of diabetes with insulin The aim oftreatment is to achieve the best possible control ofblood-glucose concentration without making the patientobsessional and to avoid disabling hypoglycaemia; closeco-operation is needed between the patient and themedical team because good control reduces the risk ofcomplications.

Insulin preparations can be divided into 3 types:

. those of short duration which have a relativelyrapid onset of action, namely soluble insulin andthe rapid-acting insulin analogues, insulin aspart,insulin glulisine, and insulin lispro (section 6.1.1.1);

. those with an intermediate action, e.g. isophaneinsulin (section 6.1.1.2); and

. those whose action is slower in onset and lasts forlong periods, e.g. protamine zinc insulin, insulindetemir, and insulin glargine (section 6.1.1.2).

The duration of action of a particular type of insulinvaries considerably from one patient to another, andneeds to be assessed individually.

Mixtures of insulin preparations may be required andappropriate combinations have to be determined for theindividual patient. Treatment should be started with ashort-acting insulin (e.g. soluble insulin) or a rapid-act-ing insulin analogue (e.g. insulin aspart) given beforemeals with intermediate-acting or long-acting insulinonce or twice daily. Alternatively, for those who havedifficulty with, or prefer not to use, multiple injectionregimens, a mixture of premixed short-acting insulin orrapid acting insulin analogue with an intermediate-act-ing or long-acting insulin (most commonly in a propor-tion of 30% soluble insulin and 70% isophane insulin)can be given once or twice daily. The dose of short-acting or rapid-acting insulin (or the proportion of theshort-acting soluble insulin component in premixedinsulin) can be increased in those with excessive post-prandial hyperglycaemia. The dose of insulin isincreased gradually according to the patient’s individualrequirements, taking care to avoid troublesome hypo-glycaemic reactions.

Insulin requirements may be increased by infection,stress, accidental or surgical trauma, and duringpuberty. Requirements may be decreased in those

with certain endocrine disorders (e.g. Addison’s disease,hypopituitarism), or in coeliac disease.

Examples of recommended insulin regimens

. Multiple injection regimen: short-acting insulin orrapid-acting insulin analogue, before meals

With intermediate-acting or long-acting insulin,once or twice daily;

. Short-acting insulin or rapid-acting insulin analoguemixed with intermediate-acting or long-acting insu-lin, once or twice daily (before meals);

. Intermediate-acting or long-acting insulin, once ortwice daily

With or without short-acting insulin or rapid-actinginsulin before meals;

. Continuous subcutaneous insulin infusion (seebelow).

Hepatic impairment Insulin requirements may bedecreased in patients with hepatic impairment.

Renal impairment Insulin requirements may fall inpatients with renal impairment and therefore dosereduction may be necessary. The compensatoryresponse to hypoglycaemia is impaired in renal impair-ment.

Pregnancy and breast-feeding During pregnancyand breast-feeding, insulin requirements may alter anddoses should be assessed frequently by an experienceddiabetes physician. The dose of insulin generally needsto be increased in the second and third trimesters ofpregnancy. The short-acting insulin analogues, insulinaspart and insulin lispro, are not known to be harmful,and may be used during pregnancy and lactation. Thesafety of long-acting insulin analogues in pregnancy hasnot been established, therefore isophane insulin isrecommended where longer-acting insulins are needed.

Insulin administration Insulin is generally given bysubcutaneous injection; the injection site should berotated to prevent lipodystrophy. Injection devices(‘pens’) (section 6.1.1.3), which hold the insulin in acartridge and meter the required dose, are convenientto use. Insulin syringes (for use with needles) arerequired for insulins not available in cartridge form.

For intensive insulin regimens multiple subcutaneousinjections (3 or more times daily) are usually recom-mended.

Short-acting injectable insulins (soluble insulin, insulinaspart, insulin glulisine, and insulin lispro) can also begiven by continuous subcutaneous infusion using aportable infusion pump. This device delivers a contin-uous basal insulin infusion and patient-activated bolusdoses at meal times. This technique can be useful forpatients who suffer recurrent hypoglycaemia or markedmorning rise in blood-glucose concentration despiteoptimised multiple-injection regimens (see also NICEguidance, below). Patients on subcutaneous insulin infu-sion must be highly motivated, able to monitor theirblood-glucose concentration, and have expert training,advice and supervision from an experienced healthcareteam.

420 6.1.1 Insulins BNF 616

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NICE guidanceContinuous subcutaneous insulin infusionfor the treatment of diabetes mellitus (type1) (July 2008)Continuous subcutaneous insulin infusion is recom-mended as an option in adults and children over 12years with type 1 diabetes:. who suffer repeated or unpredictable hypoglyc-

aemia, whilst attempting to achieve optimalglycaemic control with multiple-injection regi-mens, or

. whose glycaemic control remains inadequate(HbA1c over 8.5%) despite optimised multiple-injection regimens (including the use of long-acting insulin analogues where appropriate).

Continuous subcutaneous insulin infusion is alsorecommended as an option for children under 12years with type 1 diabetes for whom multiple-injec-tion regimens are considered impractical or inap-propriate. Children on insulin pumps should undergoa trial of multiple-injection therapy between the agesof 12 and 18 years.

Soluble insulin by the intravenous route is reserved forurgent treatment, e.g. in diabetic ketoacidosis, and forfine control in serious illness and in the peri-operativeperiod (see under Diabetes and Surgery, below).

Units The word ‘unit’ should not be abbreviated.

Monitoring Many patients now monitor their ownblood-glucose concentrations (section 6.1.6). Sinceblood-glucose concentration varies substantiallythroughout the day, ‘normoglycaemia’ cannot alwaysbe achieved throughout a 24-hour period without caus-ing damaging hypoglycaemia. It is therefore best torecommend that patients should maintain a blood-glu-cose concentration of between 4 and 9 mmol/litre formost of the time (4–7 mmol/litre before meals and lessthan 9 mmol/litre after meals), while accepting that onoccasions, for brief periods, it will be above these values;strenuous efforts should be made to prevent the blood-glucose concentration from falling below 4 mmol/litre.Patients using multiple injection regimens should under-stand how to adjust their insulin dose according to theircarbohydrate intake. With fixed-dose insulin regimens,the carbohydrate intake needs to be regulated, andshould be distributed throughout the day to match theinsulin regimen. The intake of energy and of simple andcomplex carbohydrates should be adequate to allownormal growth and development but obesity must beavoided.

Hypoglycaemia Hypoglycaemia is a potential pro-blem with insulin therapy. All patients must be carefullyinstructed on how to avoid it.

Loss of warning of hypoglycaemia among insulin-trea-ted patients can be a serious hazard, especially fordrivers and those in dangerous occupations. Very tightcontrol of diabetes lowers the blood-glucose concentra-tion needed to trigger hypoglycaemic symptoms; anincrease in the frequency of hypoglycaemic episodesmay reduce the warning symptoms experienced by thepatient. Beta-blockers can also blunt hypoglycaemicawareness (and also delay recovery).

To restore the warning signs, episodes of hypoglycaemiamust be minimised; this involves appropriate adjust-

ment of insulin type, dose and frequency together withsuitable timing and quantity of meals and snacks.

Some patients have reported loss of hypoglycaemiawarning after transfer to human insulin. Clinical studiesdo not confirm that human insulin decreases hypoglyc-aemia awareness. If a patient believes that human insu-lin is responsible for the loss of warning it is reasonableto revert to animal insulin and essential to educate thepatient about avoiding hypoglycaemia. Great careshould be taken to specify whether a human or ananimal preparation is required.

Few patients are now treated with beef insulins; whenundertaking conversion from beef to human insulin, thetotal dose should be reduced by about 10% with carefulmonitoring for the first few days. When changingbetween pork and human-sequence insulins, a dosechange is not usually needed, but careful monitoring isstill advised.

Diabetes and surgery Perioperative control of blood-glucose concentrations in patients with type 1 diabetesis achieved via an adjustable, continuous, intravenousinfusion of insulin. Detailed local protocols should beavailable to all healthcare professionals involved in thetreatment of these patients; in general, the followingsteps should be followed:

. Give an injection of the patient’s usual insulin on thenight before the operation;

. Early on the day of the operation, start an intra-venous infusion of glucose containing potassiumchloride (provided that the patient is not hyperka-laemic) and infuse at a constant rate appropriate tothe patient’s fluid requirements (usually 125 mL perhour); make up a solution of soluble insulin in sod-ium chloride 0.9% and infuse intravenously using asyringe pump piggy-backed to the intravenous infu-sion. Glucose and potassium infusions, and insulininfusions should be made up according to locallyagreed protocols;

. The rate of the insulin infusion should be adjustedaccording to blood-glucose concentration (frequentmonitoring necessary) in line with locally agreedprotocols. Other factors affecting the rate of infu-sion include the patient’s volume depletion, cardiacfunction, and age.

Protocols should include specific instructions on how tomanage resistant cases (such as patients who are inshock or severely ill or those receiving corticosteroids orsympathomimetics) and those with hypoglycaemia.

If a syringe pump is not available, soluble insulin shouldbe added to the intravenous infusion of glucose andpotassium chloride (provided the patient is not hyper-kalaemic), and the infusion run at the rate appropriate tothe patient’s fluid requirements (usually 125 mL perhour) with the insulin dose adjusted according toblood-glucose concentration in line with locally agreedprotocols.

Once the patient starts to eat and drink, give subcuta-neous insulin before breakfast and stop intravenousinsulin 30 minutes later; the dose may need to be 10–20% more than usual if the patient is still in bed orunwell. If the patient was not previously receiving insu-lin, an appropriate initial dose is 30–40 units daily in fourdivided doses using soluble insulin before meals andintermediate-acting insulin at bedtime and the doseadjusted from day to day. Patients with hyperglycaemia


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often relapse after conversion back to subcutaneousinsulin calling for one of the following approaches:

. additional doses of soluble insulin at any of the fourinjection times (before meals or bedtime) or

. temporary addition of intravenous insulin infusion(while continuing the subcutaneous regimen) untilblood-glucose concentration is satisfactory or

. complete reversion to the intravenous regimen(especially if the patient is unwell).

6.1.1.1 Short-acting insulins

Soluble insulin is a short-acting form of insulin. Formaintenance regimens it is usual to inject it 15 to 30minutes before meals.

Soluble insulin is the most appropriate form of insulinfor use in diabetic emergencies e.g. diabetic ketoacid-osis (section 6.1.3) and at the time of surgery. It can begiven intravenously and intramuscularly, as well as sub-cutaneously.

When injected subcutaneously, soluble insulin has arapid onset of action (30 to 60 minutes), a peak actionbetween 2 and 4 hours, and a duration of action of up to8 hours.

When injected intravenously, soluble insulin has a veryshort half-life of only about 5 minutes and its effectdisappears within 30 minutes.

The rapid-acting human insulin analogues, insulinaspart, insulin glulisine, and insulin lispro have afaster onset and shorter duration of action than solubleinsulin; as a result, compared to soluble insulin, fastingand preprandial blood-glucose concentrations are alittle higher, postprandial blood-glucose concentrationis a little lower, and hypoglycaemia occurs slightly lessfrequently. Subcutaneous injection of insulin analoguesmay be convenient for those who wish to inject shortlybefore or, when necessary, shortly after a meal. Theycan also help those susceptible to hypoglycaemia beforelunch and those who eat late in the evening and areprone to nocturnal hypoglycaemia. They can also beadministered by subcutaneous infusion (see InsulinAdministration, above). Insulin aspart and insulin lisprocan be administered intravenously and can be used asalternatives to soluble insulin for diabetic emergenciesand at the time of surgery.

INSULIN(Insulin Injection; Neutral Insulin; SolubleInsulin)

A sterile solution of insulin (i.e. bovine or porcine) orof human insulin; pH 6.6–8.0

Indications diabetes mellitus; diabetic ketoacidosis(section 6.1.3)

Cautions section 6.1.1; interactions: Appendix 1(antidiabetics)

Hepatic impairment section 6.1.1

Renal impairment section 6.1.1

Pregnancy section 6.1.1

Breast-feeding section 6.1.1

Side-effects see notes above; transient oedema; localreactions and fat hypertrophy at injection site; rarelyhypersensitivity reactions including urticaria, rash;overdose causes hypoglycaemia

Dose

. By subcutaneous, intramuscular or intravenousinjection or intravenous infusion, according torequirements

Highly purified animalCounselling Show container to patient and confirm thatpatient is expecting the version dispensed

Hypurinc Bovine Neutral (Wockhardt) A

Injection, soluble insulin (bovine, highly purified)100 units/mL. Net price 10-mL vial = £18.48; car-tridges (for Autopenc Classic) 5 � 3 mL = £27.72

Hypurinc Porcine Neutral (Wockhardt) A

Injection, soluble insulin (porcine, highly purified)100 units/mL. Net price 10-mL vial = £16.80; car-tridges (for Autopenc Classic) 5 � 3 mL = £25.20

Human sequenceCounselling Show container to patient and confirm thatpatient is expecting the version dispensed

Actrapidc (Novo Nordisk) A

Injection, soluble insulin (human, pyr) 100 units/mL.Net price 10-mL vial = £7.48Note Not recommended for use in subcutaneous insulin infusionpumps—may precipitate in catheter or needle

Humulin Sc (Lilly) A

Injection, soluble insulin (human, prb) 100 units/mL.Net price 10-mL vial = £15.68; 5 � 3-mL cartridge (formost Autopenc Classic or HumaPenc) = £19.08

Insumanc Rapid (Sanofi-Aventis) A

Injection, soluble insulin (human, crb) 100 units/mL,net price 5 � 3-mL cartridge (for ClikSTARc andOptiPenc Pro 1) = £17.50; 5 � 3-mL Insumanc

Rapid OptiSetc prefilled disposable injection devices(range 2–40 units, allowing 2-unit dosage adjustment)= £17.50Note Not recommended for use in subcutaneous insulin infusionpumps

Mixed preparations

See Biphasic Isophane Insulin (section 6.1.1.2)

INSULIN ASPART(Recombinant human insulin analogue)

Indications diabetes mellitus






Side-effects see under Insulin

Dose

. By subcutaneous injection, ADULT and CHILD over 2years, immediately before meals or when necessaryshortly after meals, according to requirements

. By subcutaneous infusion, intravenous injection orintravenous infusion, ADULT and CHILD over 2 years,according to requirements

NovoRapidc (Novo Nordisk) A

Injection, insulin aspart (recombinant human insulinanalogue) 100 units/mL, net price 10-mL vial =£16.28; Penfillc cartridge (for NovoPenc devices) 5 �3-mL = £28.84; 5 � 3-mL FlexPenc prefilled


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disposable injection devices (range 1–60 units, allow-ing 1-unit dosage adjustment) = £32.00Counselling Show container to patient and confirm thatpatient is expecting the version dispensed

INSULIN GLULISINE(Recombinant human insulin analogue)








Dose

. By subcutaneous injection, ADULT and CHILD over 6years, immediately before meals or when necessaryshortly after meals, according to requirements

. By subcutaneous infusion, or intravenous infusionADULT and CHILD over 6 years, according to require-ments

Apidrac (Sanofi-Aventis) A

Injection, insulin glulisine (recombinant human insu-lin analogue) 100 units/mL, net price 10-mL vial =£16.60; 5� 3-mL cartridge (for ClikSTARc , OptiPenc

Pro 1, and Autopenc 24) = £28.30; 5 � 3-mLOptiClikc cartridge (for OptiClikc Pen) = £30.27; 5 �3-mL Apidrac Optisetc prefilled disposable injectiondevices (range 2–40 units, allowing 2-unit dosageadjustment) = £28.30; 5 � 3-mL Apidrac SoloStarc

prefilled disposable injection devices (range 1–80 units, allowing 1-unit dosage adjustment) = £25.00

Counselling Show container to patient and confirm thatpatient is expecting the version dispensed

Note The Scottish Medicines Consortium (p. 4) has advised(October 2008) that Apidrac is accepted for restricted usewithin NHS Scotland for the treatment of adults and childrenover 6 years with diabetes mellitus in whom the use of a short-acting insulin analogue is appropriate

INSULIN LISPRO(Recombinant human insulin analogue)


Cautions section 6.1.1; children (use only if benefitlikely compared to soluble insulin); interactions:Appendix 1 (antidiabetics)






Dose

. By subcutaneous injection shortly before meals orwhen necessary shortly after meals, according torequirements

. By subcutaneous infusion, or intravenous injection,or intravenous infusion, according to requirements

Humalogc (Lilly) A

Injection, insulin lispro (recombinant human insulinanalogue) 100 units/mL, net price 10-mL vial =£16.61; 5 � 3-mL cartridge (for Autopenc Classic orHumaPenc) = £28.31; 5 � 3-mL Humalogc-Penprefilled disposable injection devices (range 1–60 units, allowing 1-unit dosage adjustment) = £29.46;

5 � 3-mL Humalogc KwikPen prefilled disposableinjection devices (range 1–60 units, allowing 1-unitdosage adjustment) = £29.46Counselling Show container to patient and confirm thatpatient is expecting the version dispensed

6.1.1.2 Intermediate- and long-actinginsulins

When given by subcutaneous injection, intermediate-and long-acting insulins have an onset of action ofapproximately 1–2 hours, a maximal effect at 4–12hours, and a duration of 16–35 hours. Some are giventwice daily in conjunction with short-acting (soluble)insulin, and others are given once daily, particularly inelderly patients. Soluble insulin can be mixed withintermediate and long-acting insulins (except insulindetemir and insulin glargine) in the syringe, essentiallyretaining the properties of the two components,although there may be some blunting of the initial effectof the soluble insulin component (especially on mixingwith protamine zinc insulin, see below).

Isophane insulin is a suspension of insulin with prot-amine; it is of particular value for initiation of twice-dailyinsulin regimens. Patients usually mix isophane withsoluble insulin but ready-mixed preparations may beappropriate (biphasic isophane insulin, biphasic insu-lin aspart, or biphasic insulin lispro).

Insulin zinc suspension (30% amorphous, 70% cryst-alline) has a more prolonged duration of action.

Protamine zinc insulin is usually given once daily withshort-acting (soluble) insulin. It has the drawback ofbinding with the soluble insulin when mixed in thesame syringe and is now rarely used.

Insulin glargine and insulin detemir are both long-acting human insulin analogues with a prolonged dura-tion of action; insulin glargine is given once daily andinsulin detemir is given once or twice daily. NICE(December 2002) has recommended that insulin glar-gine should be available as an option for patients withtype 1 diabetes.

NICE (May 2009) has recommended that, if insulin isrequired in patients with type 2 diabetes, insulin detemiror insulin glargine may be considered for those:

. who require assistance with injecting insulin or

. whose lifestyle is significantly restricted by recur-rent symptomatic hypoglycaemia or

. who would otherwise need twice-daily basal insulininjections in combination with oral antidiabeticdrugs or

. who cannot use the device needed to inject iso-phane insulin.

INSULIN DETEMIR(Recombinant human insulin analogue—longacting)


Cautions section 6.1.1.1; interactions: Appendix 1(antidiabetics)





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Side-effects see under Insulin (section 6.1.1.1)

Dose. By subcutaneous injection, ADULT and CHILD over 6

years, according to requirements

Levemirc (Novo Nordisk) A

Injection, insulin detemir (recombinant human insulinanalogue) 100 units/mL, net price 5 � 3-mL cartridge(for NovoPenc devices) = £42.00; 5� 3-mL FlexPenc

prefilled disposable injection device (range 1–60 units,allowing 1-unit dosage adjustment) = £42.00; 5 � 3-mL Levemir InnoLetc prefilled disposable injectiondevices (range 1–50 units, allowing 1-unit dosageadjustment) = £44.85Counselling Show container to patient and confirm thatpatient is expecting the version dispensed

INSULIN GLARGINE(Recombinant human insulin analogue—longacting)








Dose. By subcutaneous injection, ADULT and CHILD over 6

years, according to requirements

Lantusc (Sanofi-Aventis) A

Injection, insulin glargine (recombinant human insu-lin analogue) 100 units/mL, net price 10-mL vial =£26.00; 5 � 3-mL cartridge (for ClikSTARc ,OptiPenc Pro 1, and Autopenc 24) = £39.00; 5 � 3-mL OptiClikc cartridge (for OptiClikc Pen) = £40.36;5 � 3-mL Lantusc OptiSetc prefilled disposableinjection devices (range 2–40 units, allowing 2-unitdosage adjustment) = £39.00; 5 � 3-mL Lantusc

SoloStarc prefilled disposable injection devices(range 1–80 units, allowing 1-unit dosage adjustment)= £40.36Note The Scottish Medicines Consortium (p. 4) has advised(October 2002) that insulin glargine is accepted for restricteduse within NHS Scotland for the treatment of type 1 diabetes:

. in those who are at risk of or experience unacceptablefrequency or severity of nocturnal hypoglycaemia onattempting to achieve better hypoglycaemic controlduring treatment with other insulins

. as a once daily insulin therapy for patients who require acarer to administer their insulin.

It is not recommended for routine use in patients with type 2diabetes unless they suffer from recurrent episodes ofhypoglycaemia or require assistance with their insulininjections.Counselling Show container to patient and confirm thatpatient is expecting the version dispensed

INSULIN ZINC SUSPENSION(Insulin Zinc Suspension (Mixed)—long acting)

A sterile neutral suspension of bovine and/or porcine insulin orof human insulin in the form of a complex obtained by theaddition of a suitable zinc salt; consists of rhombohedralcrystals (10–40 microns) and of particles of no uniform shape(not exceeding 2 microns)








Dose. By subcutaneous injection, according to require-

ments

Highly purified animal

Hypurinc Bovine Lente (Wockhardt) A

Injection, insulin zinc suspension (bovine, highlypurified) 100 units/mL. Net price 10-mL vial = £27.72Counselling Show container to patient and confirm thatpatient is expecting the version dispensed

ISOPHANE INSULIN(Isophane Insulin Injection; Isophane Prot-amine Insulin Injection; Isophane Insulin(NPH)—intermediate acting)

A sterile suspension of bovine or porcine insulin or of humaninsulin in the form of a complex obtained by the addition ofprotamine sulphate or another suitable protamine







Side-effects see under Insulin (section 6.1.1.1); prot-amine may cause allergic reactions

Dose. By subcutaneous injection, according to require-

ments

Highly purified animalCounselling Show container to patient and confirm thatpatient is expecting the version dispensed

Hypurinc Bovine Isophane (Wockhardt) A

Injection, isophane insulin (bovine, highly purified)100 units/mL. Net price 10-mL vial = £27.72; car-tridges (for Autopenc Classic) 5 � 3 mL = £41.58

Hypurinc Porcine Isophane (Wockhardt) A

Injection, isophane insulin (porcine, highly purified)100 units/mL. Net price 10-mL vial = £25.20; car-tridges (for Autopenc Classic) 5 � 3 mL = £37.80

Human sequenceCounselling Show container to patient and confirm thatpatient is expecting the version dispensed

Insulatardc (Novo Nordisk) A

Injection, isophane insulin (human, pyr) 100 units/mL. Net price 10-mL vial = £7.48; Insulatard Penfillc

cartridge (for Novopenc devices) 5 � 3 mL = £22.90;5 � 3-mL Insulatard InnoLetc prefilled disposableinjection devices (range 1–50 units, allowing 1-unitdosage adjustment) = £20.40

Humulin Ic (Lilly) A

Injection, isophane insulin (human, prb) 100 units/mL. Net price 10-mL vial = £15.68; 5� 3-mL cartridge(for Autopenc Classic or HumaPenc) = £19.08; 5 �3-mL Humulin I-Penc prefilled disposable injectiondevices (range 1–60 units, allowing 1-unit dosageadjustment) = £28.44; 5� 3-mL Humulin I KwikPenc



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Insumanc Basal (Sanofi-Aventis) A

Injection, isophane insulin (human, crb) 100 units/mL, net price 5-mL vial = £5.61; 5 � 3-mL cartridge(for ClikSTARc and OptiPenc Pro 1) = £17.50; 5� 3-mL Insumanc Basal OptiSetc prefilled disposableinjection devices (range 2–40 units, allowing 2-unitdosage adjustment) = £17.50

Mixed preparations

See Biphasic Isophane Insulin (below)

PROTAMINE ZINC INSULIN(Protamine Zinc Insulin Injection—long acting)

A sterile suspension of insulin in the form of a complexobtained by the addition of a suitable protamine and zincchloride; this preparation was included in BP 1980 but is notincluded in BP 1988


Cautions section 6.1.1.1; see also notes above; inter-actions: Appendix 1 (antidiabetics)






Dose

. By subcutaneous injection, according to require-ments

Hypurinc Bovine Protamine Zinc (Wockhardt) A

Injection, protamine zinc insulin (bovine, highly pur-ified) 100 units/mL. Net price 10-mL vial = £27.72Counselling Show container to patient and confirm thatpatient is expecting the version dispensed

Biphasic insulins

BIPHASIC INSULIN ASPART(Intermediate-acting insulin)


Cautions see section 6.1.1.1; interactions: Appendix 1(antidiabetics)






Dose

. By subcutaneous injection, up to 10 minutes before orsoon after a meal, according to requirements

NovoMixc 30 (Novo Nordisk) A

Injection, biphasic insulin aspart (recombinanthuman insulin analogue), 30% insulin aspart, 70%insulin aspart protamine, 100 units/mL, net price 5 �3-mL Penfillc cartridges (for NovoPenc devices) =£28.84; 5 � 3-mL FlexPenc prefilled disposableinjection devices (range 1–60 units, allowing 1-unitdosage adjustment) = £32.00Counselling Show container to patient and confirm thatpatient is expecting the version dispensed; the proportions ofthe two components should be checked carefully (the orderin which the proportions are stated may not be the same inother countries)

BIPHASIC INSULIN LISPRO(Intermediate-acting insulin)


Cautions see section 6.1.1.1 and Insulin Lispro;interactions: Appendix 1 (antidiabetics)






Dose

. By subcutaneous injection, up to 15 minutes before orsoon after a meal, according to requirements

Humalogc Mix25 (Lilly) A

Injection, biphasic insulin lispro (recombinant humaninsulin analogue), 25% insulin lispro, 75% insulinlispro protamine, 100 units/mL, net price 10-mL vial= £16.61; 5� 3-mL cartridge (for Autopenc Classic orHumaPenc) = £29.46; 5 � 3-mL prefilled disposableinjection devices (range 1–60 units, allowing 1-unitdosage adjustment) = £30.98; 5 � 3-mL Humalogc

Mix25 KwikPen prefilled disposable injection devices(range 1–60 units, allowing 1-unit dosage adjustment)= £30.98Counselling Show container to patient and confirm thatpatient is expecting the version dispensed; the proportions ofthe two components should be checked carefully (the orderin which the proportions are stated may not be the same inother countries)

Humalogc Mix50 (Lilly) A

Injection, biphasic insulin lispro (recombinant humaninsulin analogue), 50% insulin lispro, 50% insulinlispro protamine, 100 units/mL, net price 5 � 3-mLcartridge (for Autopenc Classic or HumaPenc) =£29.46; 5 � 3-mL prefilled disposable injectiondevices (range 1–60 units, allowing 1-unit dosageadjustment) = £29.46; 5 � 3-mL Humalogc Mix50KwikPen prefilled disposable injection devices (range1–60 units, allowing 1-unit dosage adjustment) =£30.98Counselling Show container to patient and confirm thatpatient is expecting the version dispensed; the proportions ofthe two components should be checked carefully (the orderin which the proportions are stated may not be the same inother countries)

BIPHASIC ISOPHANE INSULIN(Biphasic Isophane Insulin Injection—inter-mediate acting)

A sterile buffered suspension of either porcine or human insulincomplexed with protamine sulphate (or another suitable prot-amine) in a solution of insulin of the same species








Dose

. By subcutaneous injection, according to require-ments


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Highly purified animalCounselling Show container to patient and confirm thatpatient is expecting the version dispensed; the proportions ofthe two components should be checked carefully (the orderin which the proportions are stated may not be the same inother countries)

Hypurinc Porcine 30/70 Mix (Wockhardt) A

Injection, biphasic isophane insulin (porcine, highlypurified), 30% soluble, 70% isophane, 100 units/mL.Net price 10-mL vial = £16.80; cartridges (for Autop-enc Classic) 5 � 3 mL = £25.20

Human sequenceCounselling Show container to patient and confirm thatpatient is expecting the version dispensed; the proportions ofthe two components should be checked carefully (the orderin which the proportions are stated may not be the same inother countries)

Humulin M3c (Lilly) A

Injection, biphasic isophane insulin (human, prb),30% soluble, 70% isophane, 100 units/mL. Net price10-mL vial = £15.68; 5 � 3-mL cartridge (for mostAutopenc Classic or HumaPenc) = £19.08; 5 � 3-mLHumulin M3 KwikPenc prefilled disposable injectiondevices (range 1–60 units, allowing 1-unit dosageadjustment) = £21.70

Insumanc Comb 15 (Sanofi-Aventis) A

Injection, biphasic isophane insulin (human, crb),15% soluble, 85% isophane, 100 units/mL, net price 5� 3-mL Insumanc Comb 15 OptiSetc prefilleddisposable injection devices (range 2–40 units, allow-ing 2-unit dosage adjustment) = £17.50


Injection, biphasic isophane insulin (human, crb),25% soluble, 75% isophane, 100 units/mL, net price5-mL vial = £5.61; 5� 3-mL cartridge (for ClikSTARc

and OptiPenc Pro 1) = £17.50; 5 � 3-mL Insumanc

Comb 25 OptiSetc prefilled disposable injectiondevices (range 2–40 units, allowing 2-unit dosageadjustment) = £17.50; 5 � 3-mL Insumanc Comb 25SoloStarc prefilled disposable injection devices(range 1–80 units, allowing 1-unit dosage adjustment)= £19.80


Injection, biphasic isophane insulin (human, crb),50% soluble, 50% isophane, 100 units/mL, net price 5� 3-mL cartridge (for ClikSTARc and OptiPenc Pro1) = £17.50; 5 � 3-mL Insumanc Comb 50 OptiSetc


6.1.1.3 Hypodermic equipment

Patients should be advised on the safe disposal oflancets, single-use syringes, and needles. Suitablearrangements for the safe disposal of contaminatedwaste must be made before these products are pre-scribed for patients who are carriers of infectious dis-eases.

Injection devicesAutopenc (Owen Mumford)

Injection device, Autopenc 24 (for use with Sanofi-Aventis3-mL insulin cartridges), allowing 1-unit dosage adjustment,max. 21 units (single-unit version) or 2-unit dosage adjust-ment, max. 42 units (2-unit version), net price (both) =£15.73; AutopencClassic (for use with Lilly and Wockhardt3-mL insulin cartridges), allowing 1-unit dosage adjustment,max. 21 units (single-unit version) or 2-unit dosage adjust-ment, max. 42 units (2-unit version), net price (all) = £15.97

ClikSTARc (Sanofi-Aventis)

Injection device, for use with Lantusc , Apidrac , andInsumanc 3-mL insulin cartridges; allowing 1-unitdose adjustment, max. 80 units, net price = £25.00

HumaPenc Luxura (Lilly)

Injection device, for use with Humulinc and Humalogc 3-mL cartridges; allowing 1-unit dosage adjustment, max.60 units, net price = £26.36

HumaPenc Luxura HD (Lilly)

Injection device, for use with Humulinc and Humalogc 3-mL cartridges; allowing 0.5-unit dosage adjustment, max.30 units, net price = £26.36

NovoPenc (Novo Nordisk)

Injection device; for use with Penfillc insulin cartridges;NovoPenc Junior (for 3-mL cartridges), allowing 0.5-unitdosage adjustment, max. 35 units, net price = £24.79;NovoPenc 3 Demi (for 3-mL cartridges), allowing 0.5-unitdosage adjustment, max. 35 units, net price = £25.21;NovoPenc 4 (for 3-mL cartridges), allowing 1-unit dosageadjustment, max. 60 units, net price = £26.56

OptiClikc (Sanofi-Aventis)

Injection device, for use with Lantus OptiClikc or ApidraOpticlikc insulin cartridges, allowing 1-unit dosage adjust-ment, max. 80 units, net price = £20.13

OptiPenc Pro 1 (Sanofi-Aventis)

Injection device, for use with Insumanc insulin cartridges;allowing 1-unit dosage adjustment, max. 60 units, net price =£22.00

LancetsLancets—sterile, single use (Drug Tariff)

1Ascensia Microletc 100 = £3.76, 200 = £7.17; BD Micro-Finec+ 100 = £3.16, 200 = £6.13; CareSensc 100 = £2.95;Cleanlet Finec 100 = £3.19, 200 = £6.13; Fastclixc 204 =£9.20; 1Finepointc 100 = £3.54; 1FreeStylec 200 = £7.02;1Milward Steri-Letc , 23 gauge, 100 = £3.00, 200 = £5.70, 28gauge, 100 = £3.00, 200 = £5.70; 1Monoletc 100 = £3.28, 200= £6.24; Monolet Extrac 100 = £3.28; MPD Ultra Thinc 100= £3.30, 200 = £6.50; Multiclixc 204 = £9.27; One TouchComfortc 200 = £7.22; 1One Touch UltraSoftc 100 = £3.61;2Softclixc 200 = £7.40; 2Softclix XLc 50 = £1.85; ThinLancets (formerly MediSense Thinc ), 200 = £7.16; 1UniletComforTouchc 100 = £3.60, 200 = £6.83; Unilet Ecoc 100 =£2.94, 200 = £5.49; 1Unilet General Purpose Superlitec 100= £3.67, 200 = £6.96; Unistik 3 Comfortc , 28-gauge, 100 =£6.24, 200 = £12.20; Unistik 3 Extrac , 21-gauge, 100 = £6.24,200 = £12.20; Unistik 3 Normalc , 23-gauge, 100 = £6.24,200 = £12.20; Universalc (formerly VitalCarec ), 200 =£6.37; Vitrex Softc , 23-gauge, 100 = £3.00, 200 = £5.70;Vitrex Gentlec 28-gauge, 100 = £3.19, 200 = £6.13;WaveSense Ultra-Thinc , 28-gauge, 200 = £6.90, 33-gauge,200 = £6.90

Compatible finger-pricking devices (unless indicated otherwise,see footnotes), all D: B-D Optimusc , Glucoletc , Monojectorc ,Penlet IIc , Soft Touchc

1. D Autoletc and D Autolet Impressionc are alsocompatible finger-pricking devices

2. Use D Softclixc finger-pricking device

NeedlesHypodermic Needle, Sterile single use (Drug Tariff)

For use with reusable glass syringe, sizes 0.5 mm (25G),0.45 mm (26G), 0.4 mm (27G). Net price 100-needle pack =£2.74

Brands include Microlancec , Monojectc


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Needles for Prefilled and Reusable Pen Injectors (DrugTariff)

Screw on, needle length 6.1 mm or less, net price 100-needlepack = £12.53; 6.2–9.9 mm, 100-needle pack = £8.89; 10 mmor more, 100-needle pack = £8.89

Brands include BD Micro-Finec +, NovoFinec , NovoTwistc ,Unifinec Pentips

Snap on, needle length 6.1 mm or less, net price 100-needlepack = £12.02; 6.2–9.9 mm, 100-needle pack = £8.52; 10 mmor more, 100-needle pack = £8.52

Brands include Penfinec

SyringesHypodermic Syringe (Drug Tariff)

Calibrated glass with Luer taper conical fitting, for use withU100 insulin. Net price 0.5 mL and 1 mL = £9.22

Brands include Abcarec

Pre-Set U100 Insulin Syringe (Drug Tariff)

Calibrated glass with Luer taper conical fitting, supplied withdosage chart and strong box, for blind patients. Net price1 mL = £21.99

U100 Insulin Syringe with Needle (Drug Tariff)

Disposable with fixed or separate needle for single use orsingle patient-use, colour coded orange. Needle length 8 mm,diameters 0.33 mm (29G), 0.3 mm (30G), net price 10 (withneedle), 0.3 mL = £1.38, 0.5 mL = £1.33, 1 mL = £1.32; needlelength 12 mm, diameters 0.45 mm (26G), 0.4 mm (27G),0.36 mm (28G), 0.33 mm (29G), net price 10 (with needle),0.3 mL = £1.45; 0.5 mL = £1.43; 1 mL = £1.44

Brands include BD Micro-Finec+, Clinipakc , Insupakc , Mono-jectc Ultra, Omnikanc , Plastipakc

AccessoriesNeedle Clipping (Chopping) Device (Drug Tariff)

Consisting of a clipper to remove needle from its hub andcontainer from which cut-off needles cannot be retrieved;designed to hold 1500 needles, not suitable for use withlancets. Net price = £1.35

Brands include BD Safe-Clipc

Sharpsguard (Drug Tariff)

Net price 1-litre sharpsbin = 85p

6.1.2 Antidiabetic drugs

6.1.2.1 Sulfonylureas

6.1.2.2 Biguanides

6.1.2.3 Other antidiabetic drugs

Oral antidiabetic drugs are used for the treatment oftype 2 diabetes mellitus. They should be prescribed onlyif the patient fails to respond adequately to at least 3months’ restriction of energy and carbohydrate intakeand an increase in physical activity. They should be usedto augment the effect of diet and exercise, and not toreplace them.

For patients not adequately controlled by diet and oralhypoglycaemic drugs, insulin may be added to thetreatment regimen or substituted for oral therapy.When insulin is added to oral therapy, it is generallygiven at bedtime as isophane or long-acting insulin, andwhen insulin replaces an oral regimen it may be given astwice-daily injections of a biphasic insulin (or isophaneinsulin mixed with soluble insulin), or a multiple injec-tion regimen. Weight gain and hypoglycaemia may becomplications of insulin therapy but weight gain may bereduced if the insulin is given in combination with met-formin.

Exenatide and liraglutide, both given by subcutaneousinjection, are also available for the treatment of type 2diabetes, see section 6.1.2.3.

Pregnancy and breast-feeding During pregnancy,women with pre-existing diabetes can be treated withmetformin [unlicensed use], either alone or in combina-tion with insulin (section 6.1.1). Metformin can becontinued, or glibenclamide resumed, during breast-feeding for those with pre-existing diabetes. Womenwith gestational diabetes may be treated, with or with-out concomitant insulin (section 6.1.1), with gliben-clamide from 11 weeks gestation (after organogenesis)[unlicensed use] or with metformin [unlicensed use].Women with gestational diabetes should discontinuehypoglycaemic treatment after giving birth.

Other oral hypoglycaemic drugs, exenatide, and liraglu-tide are contra-indicated in pregnancy.

6.1.2.1 Sulfonylureas

The sulfonylureas act mainly by augmenting insulinsecretion and consequently are effective only whensome residual pancreatic beta-cell activity is present;during long-term administration they also have anextrapancreatic action. All may cause hypoglycaemiabut this is uncommon and usually indicates excessivedosage. Sulfonylurea-induced hypoglycaemia may per-sist for many hours and must always be treated inhospital.

Sulfonylureas are considered for patients who are notoverweight, or in whom metformin is contra-indicatedor not tolerated. Several sulfonylureas are available andchoice is determined by side-effects and the duration ofaction as well as the patient’s age and renal function.Glibenclamide, a long-acting sulfonylurea, is associatedwith a greater risk of hypoglycaemia; for this reason itshould be avoided in the elderly, and shorter-actingalternatives, such as gliclazide or tolbutamide, shouldbe used instead.

When the combination of strict diet and sulfonylureatreatment fails, other options include:

. combining with metformin (section 6.1.2.2) (reportsof increased hazard with this combination remainunconfirmed);

. combining with pioglitazone, but see section6.1.2.3;

. combining with saxagliptin, sitagliptin, or vildaglip-tin (section 6.1.2.3);

. combining with exenatide or liraglutide (section6.1.2.3);

. combining with acarbose (section 6.1.2.3), whichmay have a small beneficial effect, but flatulencecan be a problem;

. combining with bedtime isophane insulin (section6.1.1) but weight gain and hypoglycaemia canoccur.

The risk of hypoglycaemia associated with sulfonylureas(see notes above) should be discussed with the patient,especially when concomitant glucose-lowering drugsare prescribed.

Insulin therapy should be instituted temporarily duringintercurrent illness (such as myocardial infarction,coma, infection, and trauma). Sulfonylureas should be

BNF 61 6.1.2 Antidiabetic drugs 4276

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omitted on the morning of surgery; insulin is requiredbecause of the ensuing hyperglycaemia in these circum-stances.

Cautions Sulfonylureas can encourage weight gainand should be prescribed only if poor control andsymptoms persist despite adequate attempts at dieting;metformin (section 6.1.2.2) is considered the drug ofchoice in obese patients. Caution is needed in theelderly.

Contra-indications Sulfonylureas should be avoidedwhere possible in acute porphyria (section 9.8.2). Sulfo-nylureas are contra-indicated in the presence of keto-acidosis.

Hepatic impairment Sulfonylureas should be avoidedor a reduced dose should be used in severe hepaticimpairment, because there is an increased risk of hypo-glycaemia. Jaundice may occur.

Renal impairment Sulfonylureas should be used withcare in those with mild to moderate renal impairment,because of the hazard of hypoglycaemia; they should beavoided where possible in severe renal impairment.Glipizide should also be avoided if the patient hasboth renal and hepatic impairment. If necessary, theshort-acting drug tolbutamide can be used in renalimpairment, as can gliclazide which is principally meta-bolised in the liver, but careful monitoring of blood-glucose concentration is essential; care is required touse the lowest dose that adequately controls bloodglucose.

Pregnancy The use of sulfonylureas in pregnancyshould generally be avoided because of the risk of neo-natal hypoglycaemia; however, glibenclamide can beused during the second and third trimesters ofpregnancy in women with gestational diabetes, seesection 6.1.2.

Breast-feeding The use of sulfonylureas (exceptglibenclamide [unlicensed use], see section 6.1.2) inbreast-feeding should be avoided because there is atheoretical possibility of hypoglycaemia in the infant.

Side-effects Side-effects of sulfonylureas are gener-ally mild and infrequent and include gastro-intestinaldisturbances such as nausea, vomiting, diarrhoea, andconstipation. Hyponatraemia has been reported withglimepiride and glipizide.

Sulfonylureas can occasionally cause a disturbance inliver function, which may rarely lead to cholestaticjaundice, hepatitis, and hepatic failure. Hypersensitivityreactions can occur, usually in the first 6–8 weeks oftherapy. They consist mainly of allergic skin reactionswhich progress rarely to erythema multiforme andexfoliative dermatitis, fever, and jaundice; photosensit-ivity has rarely been reported with glipizide. Blooddisorders are also rare but may include leucopenia,thrombocytopenia, agranulocytosis, pancytopenia,haemolytic anaemia, and aplastic anaemia.

GLIBENCLAMIDEIndications type 2 diabetes mellitus

Cautions see notes above; interactions: Appendix 1(antidiabetics)

Contra-indications see notes above

Hepatic impairment see notes above

Renal impairment see notes above

Pregnancy see notes above

Breast-feeding see notes above

Side-effects see notes above

Dose. Initially 5 mg daily with or immediately after break-

fast, dose adjusted according to response (ELDERLY

avoid, see notes above); max. 15 mg daily

Glibenclamide (Non-proprietary) A

Tablets, glibenclamide 2.5 mg, net price 28-tab pack= 95p; 5 mg, 28-tab pack = £1.07

GLICLAZIDEIndications type 2 diabetes mellitus








Dose. Initially, 40–80 mg daily, adjusted according to

response; up to 160 mg as a single dose, with break-fast; higher doses divided; max. 320 mg daily

Gliclazide (Non-proprietary) A

Tablets, scored, gliclazide 80 mg, net price 28-tabpack = £1.10, 60-tab pack = £1.52Brands include DIAGLYKc

Diamicronc (Servier) A

Tablets, scored, gliclazide 80 mg, net price 60-tabpack = £4.38

Modified release

Diamicronc MR (Servier) A

Tablets, m/r, gliclazide 30 mg, net price 28-tab pack =£2.81, 56-tab pack = £5.62. Label: 25Dose initially 30 mg daily with breakfast, adjusted according toresponse every 4 weeks (after 2 weeks if no decrease in bloodglucose); max. 120 mg daily

Note Diamicronc MR 30 mg may be considered to beapproximately equivalent in therapeutic effect to standardformulation Diamicronc 80 mg

GLIMEPIRIDEIndications type 2 diabetes mellitus

Cautions see notes above; manufacturer recommendsregular hepatic and haematological monitoring butlimited evidence of clinical value; interactions:Appendix 1 (antidiabetics)







Dose. Initially 1 mg daily, adjusted according to response in

1-mg steps at 1–2 week intervals; usual max. 4 mgdaily (exceptionally, up to 6 mg daily may be used);taken shortly before or with first main meal

428 6.1.2 Antidiabetic drugs BNF 616

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Glimepiride (Non-proprietary) A

Tablets, glimepiride 1 mg, net price 30-tab pack =£1.40; 2 mg, 30-tab pack = £1.38; 3 mg, 30-tab pack =£4.57; 4 mg, 30-tab pack = £1.75

Amarylc (Sanofi-Aventis) A

Tablets, all scored, glimepiride 1 mg (pink), net price30-tab pack = £4.33; 2 mg (green), 30-tab pack =£7.13; 3 mg (yellow), 30-tab pack = £10.75; 4 mg(blue), 30-tab pack = £14.24

GLIPIZIDE

Indications type 2 diabetes mellitus







Side-effects see notes above; also dizziness, drowsi-ness

Dose

. Initially 2.5–5 mg daily shortly before breakfast orlunch, adjusted according to response; max. 20 mgdaily; up to 15 mg may be given as a single dose;higher doses divided

Glipizide (Non-proprietary) A

Tablets, glipizide 5 mg, net price 56-tab pack = £4.23

Minodiabc (Pharmacia) A

Tablets, scored, glipizide 5 mg, net price 28-tab pack= £1.26

TOLBUTAMIDE

Indications type 2 diabetes mellitus







Side-effects see notes above; also headache, tinnitus

Dose

. 0.5–1.5 g (max. 2 g) daily in divided doses with orimmediately after meals or as a single dose with orimmediately after breakfast

Tolbutamide (Non-proprietary) A

Tablets, tolbutamide 500 mg, net price 28-tab pack =£1.74

6.1.2.2 Biguanides

Metformin, the only available biguanide, has a differentmode of action from the sulfonylureas, and is not inter-changeable with them. It exerts its effect mainly bydecreasing gluconeogenesis and by increasing periph-eral utilisation of glucose; since it acts only in thepresence of endogenous insulin it is effective only if

there are some residual functioning pancreatic isletcells.

Metformin is the drug of first choice in overweightpatients in whom strict dieting has failed to controldiabetes, if appropriate it may also be considered asan option in patients who are not overweight. It is alsoused when diabetes is inadequately controlled withsulfonylurea treatment. When the combination of strictdiet and metformin treatment fails, other optionsinclude:

. combining with a sulfonylurea (section 6.1.2.1)(reports of increased hazard with this combinationremain unconfirmed);

. combining with pioglitazone (section 6.1.2.3);

. combining with repaglinide or nateglinide (section6.1.2.3);

. combining with saxagliptin, sitagliptin, or vildaglip-tin (section 6.1.2.3);

. combining with exenatide or liraglutide (section6.1.2.3);

. combining with acarbose (section 6.1.2.3), whichmay have a small beneficial effect, but flatulencecan be a problem;

. combining with insulin (section 6.1.1) but weightgain and hypoglycaemia can be problems (weightgain minimised if insulin given at night).

Insulin treatment is almost always required in medicaland surgical emergencies; insulin should also be sub-stituted before elective surgery (omit metformin on themorning of surgery and give insulin if required).

Hypoglycaemia does not usually occur with metformin;other advantages are the lower incidence of weight gainand lower plasma-insulin concentration. It does notexert a hypoglycaemic action in non-diabetic subjectsunless given in overdose.

Gastro-intestinal side-effects are initially common withmetformin, and may persist in some patients, particu-larly when very high doses such as 3 g daily are given.

Very rarely, metformin can provoke lactic acidosis. It ismost likely to occur in patients with renal impairment,see Lactic Acidosis below.

Metformin is used for the symptomatic management ofpolycystic ovary syndrome [unlicensed indication];however, treatment should be initiated by a specialist.Metformin improves insulin sensitivity, may aid weightreduction, helps to normalise menstrual cycle (increas-ing the rate of spontaneous ovulation), and mayimprove hirsutism.

METFORMIN HYDROCHLORIDE

Indications diabetes mellitus (see notes above); poly-cystic ovary syndrome [unlicensed indication]

Cautions see notes above; determine renal functionbefore treatment and at least annually (at least twice ayear in patients with additional risk factors for renalimpairment, or if deterioration suspected); interac-tions: Appendix 1 (antidiabetics)Lactic acidosis Use with caution in renal impairment—increased risk of lactic acidosis; avoid in significant renalimpairment. NICE1 recommends that the dose should bereviewed if eGFR less than 45 mL/minute/1.73 m2 and to

1. NICE clinical guideline 87 (May 2009): Type 2 diabetes:The management of type 2 diabetes


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avoid if eGFR less than 30 mL/minute/1.73 m2. Withdraw orinterrupt treatment in those at risk of tissue hypoxia orsudden deterioration in renal function, such as those withdehydration, severe infection, shock, sepsis, acute heartfailure, respiratory failure or hepatic impairment, or thosewho have recently had a myocardial infarction

Contra-indications ketoacidosis, see also Lactic Aci-dosis above; use of general anaesthesia (suspendmetformin on the morning of surgery and restartwhen renal function returns to baseline)Iodine-containing X-ray contrast media Intravascularadministration of iodinated contrast agents can cause renalfailure. Suspend metformin prior to the test; restart at least48 hours after the test if renal function has returned tobaseline

Hepatic impairment withdraw if tissue hypoxia likely

Renal impairment see under Cautions

Pregnancy used in pregnancy for both pre-existingand gestational diabetes—see also p. 427

Breast-feeding may be used during breast-feeding—see p. 427

Side-effects anorexia, nausea, vomiting, diarrhoea(usually transient), abdominal pain, taste disturbance,rarely lactic acidosis (withdraw treatment), decreasedvitamin-B12 absorption, erythema, pruritus and urti-caria; hepatitis also reported

Dose

. Diabetes mellitus, ADULT and CHILD over 10 yearsinitially 500 mg with breakfast for at least 1 week then500 mg with breakfast and evening meal for at least 1week then 500 mg with breakfast, lunch and eveningmeal; usual max. 2 g daily in divided doses

. Polycystic ovary syndrome [unlicensed], initially500 mg with breakfast for 1 week, then 500 mg withbreakfast and evening meal for 1 week, then 1.5–1.7 gdaily in 2–3 divided doses

Note Metformin doses in the BNF may differ from those in theproduct literature

Metformin (Non-proprietary) A

Tablets, coated, metformin hydrochloride 500 mg, netprice 28-tab pack = £1.07, 84-tab pack = £1.57;850 mg, 56-tab pack = £1.67. Label: 21

Oral solution, sugar-free, metformin hydrochloride500 mg/5 mL, net price 100 mL = £62.48. Label: 21Brands include Metsolc

Glucophagec (Merck Serono) A

Tablets, f /c, metformin hydrochloride 500 mg, netprice 84-tab pack = £2.88; 850 mg, 56-tab pack =£3.20. Label: 21

Oral powder, sugar-free, metformin hydrochloride500 mg/sachet, net price 30-sachet pack = £3.29, 60-sachet pack = £6.58; 1 g/sachet, 30-sachet pack =£6.58, 60-sachet pack = £13.16. Label: 13, 21, coun-selling, administrationExcipients include aspartame (section 9.4.1)

Counselling The contents of each sachet should be mixed with150 mL of water and taken immediately

The Scottish Medicines Consortium (p. 4) has advised (March2010) that Glucophagec oral powder is accepted for restricteduse within NHS Scotland for the treatment of type 2 diabetesmellitus in patients who are unable to swallow the solid dosageform.

Modified release

Metformin (Non-Proprietary)

Tablets, m/r, metformin hydrochloride 500 mg, netprice 28 tab-pack = £3.07, 56 tab-pack = £6.14.Label: 21, 25Dose initially 500 mg once daily, increased every 10–15 days,max. 2 g once daily with evening meal; if control not achieved, use

1 g twice daily with meals, and if control still not achieved changeto standard-release tablets

Note Patients taking up to 2 g daily of the standard-release met-formin may start with the same daily dose of metformin modifiedrelease; not suitable if dose of standard-release tablets more than2 g dailyBrands include Bolamync SR, Metabetc SR

Glucophagec SR (Merck Serono) A

Tablets, m/r, metformin hydrochloride 500 mg, netprice 28-tab pack = £3.07, 56-tab pack = £6.14;750 mg, 28-tab pack = £3.20, 56-tab pack = £6.40; 1 g,28-tab pack = £4.26, 56-tab pack = £8.52. Label: 21,25Dose initially 500 mg once daily, increased every 10–15 days,max. 2 g once daily with evening meal; if control not achieved, use1 g twice daily with meals, and if control still not achieved changeto standard-release tablets

Note Patients taking up to 2 g daily of the standard-release met-formin may start with the same daily dose of Glucophagec SR;not suitable if dose of standard-release tablets more than 2 g daily

The Scottish Medicines Consortium (p. 4) has advised (September2009) that Glucophagec SR is accepted for restricted use withinNHS Scotland for the treatment of type 2 diabetes mellitus in adultpatients who are intolerant of standard-release metformin, and inwhom the prolonged-release tablet allows the use of a dose ofmetformin not previously tolerated, or in patients for whom aonce daily preparation offers a clinically significant benefit.

With pioglitazone

Section 6.1.2.3

With sitagliptin

Section 6.1.2.3

With vildagliptin

Section 6.1.2.3

6.1.2.3 Other antidiabetic drugs

Acarbose, an inhibitor of intestinal alpha glucosidases,delays the digestion and absorption of starch and suc-rose; it has a small but significant effect in loweringblood glucose. Use of acarbose is usually reserved forwhen other oral hypoglycaemics are not tolerated or arecontra-indicated. Postprandial hyperglycaemia in type 1diabetes can be reduced by acarbose, but it has beenlittle used for this purpose. Flatulence deters some fromusing acarbose although this side-effect tends todecrease with time.

Nateglinide and repaglinide stimulate insulin release.Both drugs have a rapid onset of action and shortduration of activity, and should be administered shortlybefore each main meal. Repaglinide may be given asmonotherapy for patients who are not overweight or forthose in whom metformin is contra-indicated or nottolerated, or it may be given in combination with met-formin. Nateglinide is licensed only for use with met-formin.

The thiazolidinedione, pioglitazone, reduces peripheralinsulin resistance, leading to a reduction of blood-glu-cose concentration. Pioglitazone can be used alone or incombination with metformin or with a sulfonylurea (ifmetformin inappropriate), or with both; the combinationof pioglitazone plus metformin is preferred to pioglita-zone plus sulfonylurea, particularly for obese patients.Inadequate response to a combination of metformin andsulfonylurea may indicate failing insulin release; theintroduction of pioglitazone has a limited role in thesecircumstances and the initiation of insulin is often moreappropriate. Pioglitazone is also licensed in combination


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with insulin, in patients who have not achieved ade-quate glycaemic control with insulin alone, when met-formin is inappropriate. Blood-glucose control maydeteriorate temporarily when pioglitazone is substitutedfor an oral antidiabetic drug that is being used incombination with another. Long-term benefits of piogli-tazone have not yet been demonstrated. NICE (May2009) has recommended that, when glycaemic controlis inadequate with existing treatment, pioglitazone canbe added to:

. a sulfonylurea, if metformin is contra-indicated ornot tolerated;

. metformin, if risks of hypoglycaemia with sulfony-lurea are unacceptable or a sulfonylurea is contra-indicated or not tolerated;

. a combination of metformin and a sulfonylurea, ifinsulin is unacceptable because of lifestyle or otherpersonal issues, or because the patient is obese.

NICE has recommended that treatment with pioglita-zone is continued only if HbA1c concentration is reducedby at least 0.5% within 6 months of starting treatment.

The Scottish Medicines Consortium (p. 4) accepts use ofpioglitazone (February 2007) with metformin and asulfonylurea, for patients (especially if overweight)whose glycaemic control is inadequate despite the useof 2 oral hypoglycaemic drugs and who are unable orunwilling to take insulin; treatment should be initiatedand monitored by an experienced diabetes physician.

MHRA/CHM advicePioglitazone cardiovascular safety(December 2007 and January 2011)Incidence of heart failure is increased when piogli-tazone is combined with insulin especially inpatients with predisposing factors e.g. previous myo-cardial infarction. Patients who take pioglitazoneshould be closely monitored for signs of heart fail-ure; treatment should be discontinued if any dete-rioration in cardiac status occurs.Pioglitazone should not be used in patients withheart failure or a history of heart failure.

RosiglitazoneThe marketing authorisation for rosiglitazone(Avandiac , Avandametc) has been suspended(September 2010) following a review by theEuropean Medicines Agency. The European Medi-cines Agency concluded that the benefits ofrosiglitazone treatment do not outweigh the cardi-ovascular risks. Prescribers should not issue new orrepeat prescriptions for rosiglitazone. Treatment ofpatients who are taking rosiglitazone should bereviewed.

Saxagliptin, sitagliptin, and vildagliptin inhibit dipep-tidylpeptidase-4 to increase insulin secretion and lowerglucagon secretion. They are licensed for use in type 2diabetes in combination with metformin or a sulfonylur-ea (if metformin inappropriate) or pioglitazone, whentreatment with either metformin or a sulfonylurea orpioglitazone fails to achieve adequate glycaemic con-trol. Sitagliptin is also licensed for use as monotherapy(if metformin inappropriate), or in combination withboth metformin and a sulfonylurea, or both metforminand pioglitazone when dual therapy with these drugsfails to achieve adequate glycaemic control. The com-

bination of sitagliptin and insulin (with or without met-formin) is also licensed for use when a stable dose ofinsulin has not provided adequate glycaemic control.

NICE (May 2009) has recommended that, when glycae-mic control is inadequate with existing treatment:

. sitagliptin or vildagliptin (instead of a sulfonylurea)can be added to metformin, if there is a significantrisk of hypoglycaemia or if a sulfonylurea is contra-indicated or not tolerated;

. sitagliptin or vildagliptin can be added to a sulfo-nylurea, if metformin is contra-indicated or nottolerated;

. sitagliptin can be added to both metformin and asulfonylurea, if insulin is unacceptable because oflifestyle or other personal issues, or because thepatient is obese.

NICE has recommended that treatment with sitagliptinor vildagliptin is continued only if HbA1c concentrationis reduced by at least 0.5% within 6 months of startingtreatment.

The Scottish Medicines Consortium (p. 4) has advisedthat vildagliptin (Galvusc) is accepted for restricted usewithin NHS Scotland for the treatment of type 2diabetes mellitus in combination with metformin whenaddition of a sulfonylurea is inappropriate (March 2008),and also in combination with a sulfonylurea if metforminis inappropriate (September 2009).

Exenatide and liraglutide both bind to, and activate,the GLP-1 (glucagon-like peptide-1) receptor to increaseinsulin secretion, suppress glucagon secretion, and slowgastric emptying. Treatment with exenatide and liraglu-tide is associated with the prevention of weight gain andpossible promotion of weight loss which can be bene-ficial in overweight patients. They are both given bysubcutaneous injection for the treatment of type 2 dia-betes mellitus.

Exenatide is licensed in combination with metformin ora sulfonylurea, or both, or with pioglitazone, or withboth metformin and pioglitazone, in patients who havenot achieved adequate glycaemic control with thesedrugs alone or in combination.

NICE (May 2009) has recommended that, when glycae-mic control is inadequate with metformin and sulfony-lurea treatment, the addition of exenatide may be con-sidered if the patient has:

. a body mass index of 35 kg/m2 or over and is ofEuropean descent (with appropriate adjustment forother ethnic groups) and weight-related psycholo-gical or medical problems or

. a body mass index less than 35 kg/m2, and insulinwould be unacceptable for occupational reasons orweight loss would benefit other significant obesity-related comorbidities.

NICE has recommended that treatment with exenatideis continued only if HbA1c concentration is reduced by atleast 1% and a weight loss of at least 3% is achievedwithin 6 months of starting treatment.

The Scottish Medicines Consortium (p. 4) has advised(June 2007) that exenatide (Byettac) is accepted forrestricted use within NHS Scotland for the treatment oftype 2 diabetes in combination with metformin orsulfonylurea (or both), as an alternative to treatmentwith insulin in patients where treatment with metforminor sulfonylurea (or both) at maximally tolerated doses


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has been inadequate, and treatment with insulin wouldbe the next option.

Liraglutide is licensed for the treatment of type 2 dia-betes mellitus in combination with metformin or asulfonylurea, or both, in patients who have not achievedadequate glycaemic control with these drugs alone or incombination. Liraglutide is also licensed for use incombination with both metformin and pioglitazonewhen dual therapy with these drugs fails to achieveadequate glycaemic control.

NICE guidanceLiraglutide for the treatment of type 2diabetes mellitus (October 2010)Liraglutide in triple therapy regimens (in combina-tion with metformin and a sulfonylurea, or met-formin and a thiazolidinedione) is recommendedfor the treatment of type 2 diabetes, only whenglycaemic control is inadequate, and the patient has:. a body mass index of 35 kg/m2 or over and is of

European descent (with appropriate adjustmentfor other ethnic groups) and weight-related psy-chological or medical problems, or

. a body mass index of less than 35 kg/m2, andinsulin would be unacceptable for occupationalreasons or weight loss would benefit other sig-nificant obesity-related comorbidities.

Treatment with liraglutide in a triple therapy regi-men should be continued only if HbA1c concentra-tion is reduced by at least 1% and a weight loss of atleast 3% is achieved within 6 months of startingtreatment.Liraglutide in dual therapy regimens (in combinationwith metformin or a sulfonylurea) is recommendedonly if:. treatment with metformin or a sulfonylurea is

contra-indicated or not tolerated, and. treatment with thiazolidinediones and dipepti-

dylpeptidase-4 inhibitors is contra-indicated ornot tolerated.

Liraglutide, in combination with metformin or asulfonylurea should be continued only if HbA1c con-centration is reduced by at least 1% within 6 monthsof starting treatment.Liraglutide 1.8 mg daily is not recommended.

ACARBOSE

Indications diabetes mellitus inadequately controlledby diet or by diet with oral antidiabetic drugs

Cautions monitor liver function; may enhance hypo-glycaemic effects of insulin and sulfonylureas (hypo-glycaemic episodes may be treated with oral glucosebut not with sucrose); interactions: Appendix 1(antidiabetics)

Contra-indications inflammatory bowel disease, pre-disposition to partial intestinal obstruction; hernia,previous abdominal surgery

Hepatic impairment avoid

Renal impairment avoid if eGFR less than 25 mL/minute/1.73 m2

Pregnancy avoid

Breast-feeding avoid

Side-effects flatulence, soft stools, diarrhoea (mayneed to reduce dose or withdraw), abdominal dis-

tention and pain; rarely, nausea, abnormal liverfunction tests and skin reactions; very rarely ileus,oedema, jaundice, and hepatitisNote Antacids unlikely to be beneficial for treating side-effects

Dose

. ADULT over 18 years, initially 50 mg daily increased to50 mg 3 times daily, then increased if necessary after6–8 weeks to 100 mg 3 times daily; max. 200 mg 3times dailyCounselling Tablets should be chewed with first mouthful offood or swallowed whole with a little liquid immediatelybefore food. To counteract possible hypoglycaemia, patientsreceiving insulin or a sulfonylurea as well as acarbose needto carry glucose (not sucrose—acarbose interferes withsucrose absorption)

Glucobayc (Bayer Schering) A

Tablets, acarbose 50 mg, net price 90-tab pack =£6.15; 100 mg (scored), 90-tab pack = £11.35. Coun-selling, administration

EXENATIDE

Indications see notes above

Cautions elderly; pancreatitis (see below); interac-tions: Appendix 1 (antidiabetics)Pancreatitis Severe pancreatitis (sometimes fatal), includ-ing haemorrhagic or necrotising pancreatitis, has beenreported rarely. Patients or their carers should be told how torecognise signs and symptoms of pancreatitis and advised toseek prompt medical attention if symptoms such as abdo-minal pain, nausea, and vomiting develop; discontinue per-manently if pancreatitis is diagnosed

Contra-indications ketoacidosis; severe gastro-intes-tinal disease

Renal impairment use with caution if eGFR 30–50 mL/minute/1.73 m2; avoid if eGFR less than30 mL/minute/1.73m2

Pregnancy avoid—toxicity in animal studies

Breast-feeding avoid—no information available

Side-effects gastro-intestinal disturbances includingnausea, vomiting, diarrhoea, dyspepsia, abdominalpain and distension, gastro-oesophageal reflux dis-ease, decreased appetite; headache, dizziness, agita-tion, asthenia; hypoglycaemia; increased sweating,injection-site reactions; antibody formation; lesscommonly pancreatitis (see Cautions above); veryrarely anaphylactic reactions; also reported consti-pation, flatulence, eructation, dehydration, taste dis-turbance, renal impairment, drowsiness, rash, pru-ritus, urticaria, and angioedema

Dose

. By subcutaneous injection, ADULT over 18 years,initially 5 micrograms twice daily within 1 hour before2 main meals (at least 6 hours apart), increased ifnecessary after at least 1 month to max. 10 micr-ograms twice dailyCounselling If a dose is missed, continue with the nextscheduled dose—do not administer after a meal. Some oralmedications should be taken at least 1 hour before or 4 hoursafter exenatide injection—consult product literature fordetails

Byettac (Lilly) T A

Injection, exenatide 250 micrograms/mL, net price5 microgram/dose prefilled pen (60 doses) = £68.24,10 microgram/dose prefilled pen (60 doses) = £68.24.Counselling, administration


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LIRAGLUTIDE


Cautions discontinue if symptoms of acute pancreat-itis (persistent, severe abdominal pain); interactions:Appendix 1 (antidiabetics)

Contra-indications ketoacidosis; inflammatory boweldisease; diabetic gastroparesis

Hepatic impairment avoid—limited experience

Renal impairment avoid if eGFR less than 60 mL/minute/1.73 m2—limited experience


Breast-feeding avoid—no information available

Side-effects gastro-intestinal disturbances includingnausea, vomiting, constipation, diarrhoea, dyspepsia,abdominal pain and distension, flatulence, gastritis,gastro-oesophageal reflux disease, decreased appe-tite; headache, dizziness, fatigue; fever, bronchitis,nasopharyngitis; hypoglycaemia; injection site reac-tions; also reported acute pancreatitis, thyroid neo-plasm, goitre, increased blood calcitonin, angioedema

Dose

. By subcutaneous injection, ADULT over 18 years,initially 0.6 mg once daily, increased after at least 1week to 1.2 mg once daily, further increased ifnecessary after an interval of at least 1 week to max.1.8 mg once dailyNote Dose of concomitant sulfonylurea may need to bereduced

Victozac (Novo Nordisk) T A

Injection, liraglutide 6 mg/mL, net price 2 � 3-mLprefilled pens = £78.48, 3 � 3-mL prefilled pens =£117.72. Counselling, administration

NATEGLINIDE

Indications type 2 diabetes mellitus in combinationwith metformin (section 6.1.2.2) when metforminalone inadequate

Cautions substitute insulin during intercurrent illness(such as myocardial infarction, coma, infection, andtrauma) and during surgery (omit nateglinide onmorning of surgery and recommence when eating anddrinking normally); elderly, debilitated and malnour-ished patients; interactions: Appendix 1 (anti-diabetics)

Contra-indications ketoacidosis

Hepatic impairment caution in moderate hepaticimpairment; avoid in severe impairment—no infor-mation available


Breast-feeding avoid—present in milk in animalstudies

Side-effects hypoglycaemia; hypersensitivity reac-tions including pruritus, rashes and urticaria

Dose

. ADULT over 18 years, initially 60 mg 3 times dailywithin 30 minutes before main meals, adjustedaccording to response up to max. 180 mg 3 times daily

Starlixc (Novartis) A

Tablets, f/c, nateglinide 60 mg (pink), net price 84-tabpack = £22.71; 120 mg (yellow), 84-tab pack = £25.88;180 mg (red), 84-tab pack = £25.88

PIOGLITAZONE

Indications type 2 diabetes mellitus (alone or com-bined with metformin or a sulfonylurea, or with both,or with insulin—see also notes above)

Cautions monitor liver function (see below); cardio-vascular disease or in combination with insulin (risk ofheart failure—see MHRA/CHM advice p. 431); sub-stitute insulin during peri-operative period (omit pio-glitazone on morning of surgery and recommencewhen eating and drinking normally); increased risk ofbone fractures, particularly in women; avoid in acuteporphyria (but see section 9.8.2); interactions:Appendix 1 (antidiabetics)Liver toxicity Rare reports of liver dysfunction; monitorliver function before treatment, and periodically thereafter;advise patients to seek immediate medical attention ifsymptoms such as nausea, vomiting, abdominal pain, fatigueand dark urine develop; discontinue if jaundice occurs

Contra-indications history of heart failure

Hepatic impairment avoid; see also Cautions above



Side-effects gastro-intestinal disturbances, weightgain, oedema, anaemia, headache, visual distur-bances, dizziness, arthralgia, hypoaesthesia, haema-turia, impotence; less commonly hypoglycaemia,fatigue, insomnia, vertigo, sweating, altered bloodlipids, proteinuria; see also Liver Toxicity above

Dose

. ADULT over 18 years, initially 15–30 mg once dailyincreased to 45 mg once daily according to responseNote Dose of concomitant sulfonylurea or insulin may needto be reduced

Actosc (Takeda) T A

Tablets, pioglitazone (as hydrochloride) 15 mg, netprice 28-tab pack = £25.83; 30 mg, 28-tab pack =£35.89; 45 mg, 28-tab pack = £39.55

With metformin

For prescribing information on metformin, see section6.1.2.2

Competactc (Takeda) T A

Tablets, f/c, pioglitazone (as hydrochloride) 15 mg,metformin hydrochloride 850 mg, net price 56-tabpack = £35.89. Label: 21Dose ADULT over 18 years, type 2 diabetes not controlled bymetformin alone, 1 tablet twice daily

Note Titration with the individual components (pioglitazone andmetformin) desirable before initiating Competactc

REPAGLINIDE

Indications type 2 diabetes mellitus (as monotherapyor in combination with metformin when metforminalone inadequate)

Cautions substitute insulin during intercurrent illness(such as myocardial infarction, coma, infection, andtrauma) and during surgery (omit repaglinide onmorning of surgery and recommence when eating anddrinking normally); debilitated and malnourishedpatients; interactions: Appendix 1 (antidiabetics)


Hepatic impairment avoid in severe liver disease

Renal impairment use with caution

Pregnancy avoid


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Side-effects abdominal pain, diarrhoea, constipation,nausea, vomiting; rarely hypoglycaemia, hypersensi-tivity reactions including pruritus, rashes, vasculitis,urticaria, and visual disturbances

Dose

. ADULT over 18 years, initially 500 micrograms within30 minutes before main meals (1 mg if transferringfrom another oral hypoglycaemic), adjusted accordingto response at intervals of 1–2 weeks; up to 4 mg maybe given as a single dose, max. 16 mg daily; ELDERLY

over 75 years, not recommended

Prandinc (Daiichi Sankyo) A

Tablets, repaglinide 500 micrograms, net price 30-tabpack = £3.92, 90-tab pack = £11.76; 1 mg (yellow), 30-tab pack = £3.92, 90-tab pack = £11.76; 2 mg (peach),90-tab pack = £11.76Formerly marketed as NovoNormc

SAXAGLIPTIN


Cautions elderly; interactions: Appendix 1 (anti-diabetics)

Hepatic impairment use with caution in moderateimpairment; avoid in severe impairment

Renal impairment avoid if eGFR less than 50 mL/minute/1.73m2

Pregnancy avoid unless essential—toxicity in animalstudies


Side-effects vomiting, dyspepsia, gastritis; peripheraloedema; headache, dizziness, fatigue; upper respir-atory tract infection, urinary tract infection, gastro-enteritis, sinusitis, nasopharyngitis; hypoglycaemia,myalgia; less commonly dyslipidaemia, hypertrigly-ceridaemia, erectile dysfunction, arthralgia; alsoreported rash

Dose

. ADULT over 18 years, 5 mg once dailyNote Dose of concomitant sulfonylurea may need to bereduced

Onglyzac (Bristol-Myers Squibb) T A

Tablets, pink, f/c, saxagliptin (as hydrochloride) 5 mg,net price 28-tab pack = £31.60

SITAGLIPTIN


Cautions interactions: Appendix 1 (antidiabetics)





Side-effects gastro-intestinal disturbances; peripheraloedema; upper respiratory tract infection, nasophar-yngitis; pain; less commonly dry mouth, anorexia,headache, drowsiness, dizziness, hypoglycaemia,osteoarthritis; also reported pancreatitis, rash, cuta-neous vasculitis, and Stevens-Johnson syndrome

Dose

. ADULT over 18 years, 100 mg once dailyNote Dose of concomitant sulfonylurea or insulin may need tobe reduced

Januviac (MSD) T A

Tablets, beige, f/c, sitagliptin (as phosphate) 100 mg,net price 28-tab pack = £33.26The Scottish Medicines Consortium (p. 4) has advised (June 2010)that Januviac is accepted for restricted use within NHS Scotlandas monotherapy, to improve glycaemic control in patients withtype 2 diabetes mellitus, for whom both metformin andsulfonylureas are not appropriate

With metformin

For prescribing information on metformin, see section6.1.2.2

Janumetc (MSD) T A

Tablets, f/c, red, sitagliptin 50 mg, metformin hydro-chloride 1 g, net price 56-tab pack = £34.56. Label: 21Dose type 2 diabetes mellitus not controlled by metformin aloneor by metformin in combination with either a sulfonylurea orpioglitazone or insulin, ADULT over 18 years, 1 tablet twice daily

Note Dose of concomitant sulfonylurea or insulin may need to bereduced

The Scottish Medicines Consortium (p. 4) has advised (July 2008)that Janumetc is accepted for restricted use within NHS Scotlandfor the treatment of type 2 diabetes mellitus when the addition of asulfonylurea to metformin is not appropriate; it is also acceptedfor use in NHS Scotland in combination with a sulfonylurea inpatients inadequately controlled on maximum tolerated doses ofmetformin and a sulfonylurea.

VILDAGLIPTIN

Indications type 2 diabetes mellitus (in combinationwith metformin or with a sulfonylurea or with piogli-tazone—see also notes above)

Cautions elderly; monitor liver function (see below);heart failure (avoid if moderate or severe); interac-tions: Appendix 1 (antidiabetics)Liver toxicity Rare reports of liver dysfunction; monitorliver function before treatment and every 3 months for firstyear and periodically thereafter; advise patients to seekprompt medical attention if symptoms such as nausea,vomiting, abdominal pain, fatigue, and dark urine develop;discontinue if jaundice or other signs of liver dysfunctionoccur


Hepatic impairment avoid; see also Cautions above




Side-effects nausea, peripheral oedema, headache,tremor, asthenia, dizziness; less commonly constipa-tion, hypoglycaemia, arthralgia; rarely hepatic dys-function (see also Liver Toxicity above); very rarelynasopharyngitis, upper respiratory tract infection;pancreatitis also reported

Dose

. ADULT over 18 years, in combination with metformin orpioglitazone, 50 mg twice daily; in combination with asulfonylurea, 50 mg daily in the morning

Galvusc (Novartis) T A

Tablets, pale yellow, vildagliptin 50 mg, net price 56-tab pack = £31.76


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With metforminFor prescribing information on metformin, see section6.1.2.2

Eucreasc (Novartis) T A

Eucreasc 50 mg/850 mg tablets, f/c, yellow, vilda-gliptin 50 mg, metformin hydrochloride 850 mg, netprice 60-tab pack = £31.76. Label: 21

Eucreasc 50 mg/1 g tablets, f/c, dark yellow,vildagliptin 50 mg, metformin hydrochloride 1 g, netprice 60-tab pack = £31.76. Label: 21Dose type 2 diabetes mellitus not controlled by metformin alone,ADULT over 18 years, 1 Eucreasc tablet twice daily (based onpatient’s current metformin dose)

The Scottish Medicines Consortium (p. 4) has advised (June 2008)that Eucreasc is accepted for restricted use within NHS Scotlandfor the treatment of type 2 diabetes mellitus in patients unable toachieve adequate glycaemic control with metformin alone orthose already treated with vildagliptin and metformin as separatetablets

6.1.3 Diabetic ketoacidosis

The management of diabetic ketoacidosis involves thereplacement of fluid and electrolytes and the adminis-tration of insulin. Guidelines for the Management ofDiabetic Ketoacidosis in Adults, published by the JointBritish Diabetes Societies Inpatient Care Group1, shouldbe followed.

. To restore circulating volume if systolic blood pres-sure is below 90 mmHg (adjusted for age, sex, andmedication as appropriate), give 500 mL sodiumchloride 0.9% by intravenous infusion over 10–15minutes; repeat if blood pressure remains below90 mmHg and seek senior medical advice.

. When blood pressure is over 90 mmHg, sodiumchloride 0.9% should be given by intravenous infu-sion at a rate that replaces deficit and providesmaintenance; see guideline for suggested regimen.

. Include potassium chloride in the fluids unlessanuria is suspected; adjust according to plasma-potassium concentration (measure at 60 minutes,2 hours, and 2 hourly thereafter; measure hourly ifoutside the normal range).

. Start an intravenous insulin infusion: soluble insu-lin should be diluted (and mixed thoroughly) withsodium chloride 0.9% intravenous infusion to aconcentration of 1 unit/mL; infuse at a fixed rate of0.1 units/kg/hour.

. Established subcutaneous therapy with long-actinginsulin analogues (insulin detemir or insulin glar-gine) should be continued during treatment of dia-betic ketoacidosis.

. Monitor blood-ketone and blood-glucose concen-trations hourly and adjust the insulin infusion rateaccordingly. Blood-ketone concentration should fallby at least 0.5 mmol/litre/hour and blood-glucoseconcentration should fall by at least 3 mmol/litre/hour.

. Once blood-glucose concentration falls below14 mmol/litre, glucose 10% should be given byintravenous infusion (into a large vein through alarge-gauge needle) at a rate of 125 mL/hour, inaddition to the sodium chloride 0.9% infusion.

. Continue insulin infusion until blood-ketone con-centration is below 0.3 mmol/litre, blood pH is

above 7.3 and the patient is able to eat and drink;ideally give subcutaneous fast-acting insulin and ameal, and stop the insulin infusion 1 hour later.

For the management of diabetic ketoacidosis in childrenunder 18 years, see BNF for Children.

The management of hyperosmolar hyperglycaemicstate or hyperosmolar hyperglycaemic nonketoticcoma is similar to that of diabetic ketoacidosis, althoughlower rates of insulin infusion are usually necessary andslower rehydration may be required.

6.1.4 Treatment ofhypoglycaemia

Initially glucose 10–20 g is given by mouth either inliquid form or as granulated sugar or sugar lumps.Approximately 10 g of glucose is available from non-diet versions of Lucozadec Energy Original 55 mL,Coca-Colac 100 mL, Ribenac Blackcurrant 18 mL (tobe diluted), 2 teaspoons of sugar, and also from 3 sugarlumps2. If necessary this may be repeated in 10–15minutes. After initial treatment, a snack providingsustained availability of carbohydrate (e.g. a sandwich,fruit, milk, or biscuits) or the next meal, if it is due, canprevent blood-glucose concentration from falling again.

Hypoglycaemia which causes unconsciousness is anemergency. Glucagon, a polypeptide hormone pro-duced by the alpha cells of the islets of Langerhans,increases plasma-glucose concentration by mobilisingglycogen stored in the liver. In hypoglycaemia, if sugarcannot be given by mouth, glucagon can be given byinjection. Carbohydrates should be given as soon aspossible to restore liver glycogen; glucagon is not appro-priate for chronic hypoglycaemia. Glucagon may beissued to close relatives of insulin-treated patients foremergency use in hypoglycaemic attacks. It is oftenadvisable to prescribe on an ‘if necessary’ basis tohospitalised insulin-treated patients, so that it may begiven rapidly by the nurses during an hypoglycaemicemergency. If not effective in 10 minutes intravenousglucose should be given.

Alternatively, 50 mL of glucose intravenous infusion20% (section 9.2.2) may be given intravenously into alarge vein through a large-gauge needle; care is requiredsince this concentration is irritant especially if extrava-sation occurs. Glucose intravenous infusion 10% mayalso be used but larger volumes are needed. Glucoseintravenous infusion 50% is not recommended becauseof the higher risk of extravasation injury and becauseadministration is difficult. Close monitoring is necessaryin the case of an overdose with a long-acting insulinbecause further administration of glucose may berequired. Patients whose hypoglycaemia is caused byan oral antidiabetic drug should be transferred to hos-pital because the hypoglycaemic effects of these drugsmay persist for many hours.

For advice on the emergency management of hypoglyc-aemia in dental practice, see p. 28.

1. Available at www.diabetes.nhs.uk

2. Proprietary products of quick-acting carbohydrate (e.g.GlucoGelc , Dextrogelc , Hypo-Fitc) are available onprescription for the patient to keep to hand in case ofhypoglycaemia.

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GLUCAGON

Indications see notes above and under Dose

Cautions see notes above, insulinoma, glucagonoma;ineffective in chronic hypoglycaemia, starvation, andadrenal insufficiency

Contra-indications phaeochromocytoma

Side-effects nausea, vomiting, abdominal pain,hypokalaemia, hypotension, rarely hypersensitivityreactions

Dose. Insulin-induced hypoglycaemia, by subcutaneous,

intramuscular, or intravenous injection, ADULT andCHILD over 8 years (or body-weight over 25 kg), 1 mg;CHILD under 8 years (or body-weight under 25 kg),500 micrograms; if no response within 10 minutesintravenous glucose must be given

. Diagnostic aid, consult product literature

. Beta-blocker poisoning, see p. 37Note 1 unit of glucagon = 1 mg of glucagon

1GlucaGenc HypoKit (Novo Nordisk) A

Injection, powder for reconstitution, glucagon (rys) ashydrochloride with lactose, net price 1-mg vial withprefilled syringe containing water for injection =£11.52

1. A restriction does not apply where administration is forsaving life in emergency

Chronic hypoglycaemia

Diazoxide, administered by mouth, is useful in themanagement of patients with chronic hypoglycaemiafrom excess endogenous insulin secretion, either froman islet cell tumour or islet cell hyperplasia. It has noplace in the management of acute hypoglycaemia.

DIAZOXIDE

Indications chronic intractable hypoglycaemia;hypertensive emergency—but no longer recom-mended, see section 2.5

Cautions ischaemic heart disease; monitor bloodpressure; during prolonged use monitor white cell andplatelet count, and in children, regularly assessgrowth, bone, and psychological development; inter-actions: Appendix 1 (diazoxide)

Renal impairment dose reduction may be required

Pregnancy prolonged use in second or third trimestersmay produce alopecia and impaired glucose tolerancein neonate; inhibits uterine activity during labour

Side-effects anorexia, nausea, vomiting, hyperuric-aemia, hypotension, oedema, tachycardia, arrhyth-mias, extrapyramidal effects; hypertrichosis on pro-longed treatment

Dose

. By mouth, ADULT and CHILD, initially 5 mg/kg daily in2–3 divided doses

Eudeminec (UCB Pharma) A

Tablets, diazoxide 50 mg. Net price 100 = £44.64

Injection, see section 2.5.1

6.1.5 Treatment of diabeticnephropathy andneuropathy

Diabetic nephropathyRegular review of diabetic patients should include anannual test for urinary protein (using Albustixc) andserum creatinine measurement. If the urinary proteintest is negative, the urine should be tested formicroalbuminuria (the earliest sign of nephropathy). Ifreagent strip tests (Micral-Test IIc D or Micro-bumintestcD) are used and prove positive, the resultshould be confirmed by laboratory analysis of a urinesample. Provided there are no contra-indications, alldiabetic patients with nephropathy causing proteinuriaor with established microalbuminuria (at least 3 positivetests) should be treated with an ACE inhibitor (section2.5.5.1) or an angiotensin-II receptor antagonist (section2.5.5.2) even if the blood pressure is normal; in any case,to minimise the risk of renal deterioration, bloodpressure should be carefully controlled (section 2.5).

ACE inhibitors can potentiate the hypoglycaemic effectof insulin and oral antidiabetic drugs; this effect is morelikely during the first weeks of combined treatment andin patients with renal impairment.

For the treatment of hypertension in diabetes, see sec-tion 2.5.

Diabetic neuropathyOptimal diabetic control is beneficial for the manage-ment of painful neuropathy in patients with type 1diabetes (see also section 4.7.3). Paracetamol (p. 259)or a non-steroidal anti-inflammatory drug such as ibu-profen (p. 636) may relieve mild to moderate pain.

Duloxetine (p. 243) is effective for the treatment ofpainful diabetic neuropathy; amitriptyline (p. 235)[unlicensed use] can be used if duloxetine is ineffectiveor unsuitable. Nortriptyline (p. 236) [unlicensed] maybe better tolerated than amitriptyline. If treatment withamitriptyline or duloxetine is inadequate, treatment withpregabalin (p. 284) should be tried. Combination ther-apy of duloxetine or amitriptyline with pregabalin can beused if monotherapy at the maximum tolerated dosedoes not control symptoms.

Neuropathic pain may respond to opioid analgesics.There is evidence of efficacy for tramadol (p. 271),morphine (p. 268), and oxycodone (p. 269); however,treatment with morphine or oxycodone should beinitiated only under specialist supervision. Tramadolcan be prescribed while the patient is waiting for assess-ment by a specialist if other treatments have beenunsuccessful.

Gabapentin (p. 284) and carbamazepine (p. 281) aresometimes used for the treatment of neuropathic pain.Capsaicin cream 0.075% (p. 664) is licensed for painfuldiabetic neuropathy and may have some effect, but itproduces an intense burning sensation during the initialtreatment period.

In autonomic neuropathy diabetic diarrhoea can oftenbe managed by 2 or 3 doses of tetracycline 250 mg[unlicensed use] (p. 347). Otherwise codeine (p. 58) is

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the best drug, but other antidiarrhoeal preparations canbe tried. An antiemetic which promotes gastric transit,such as metoclopramide (p. 253) or domperidone(p. 253), is helpful for gastroparesis. In rare caseswhen an antiemetic does not help, erythromycin (espe-cially when given intravenously) may be beneficial butthis needs confirmation.

In neuropathic postural hypotension increased saltintake and the use of the mineralocorticoid fludrocorti-sone 100–400 micrograms daily [unlicensed use](p. 442) may help by increasing plasma volume, butuncomfortable oedema is a common side-effect. Fludro-cortisone can also be combined with flurbiprofen(p. 636) and ephedrine hydrochloride (p. 179) [bothunlicensed]. Midodrine [unlicensed], an alpha agonist,may also be useful in postural hypotension.

Gustatory sweating can be treated with an anti-muscarinic such as propantheline bromide (p. 48);side-effects are common. For the management of hyper-hidrosis, see section 13.12.

In some patients with neuropathic oedema, ephedrinehydrochloride [unlicensed use] 30–60 mg 3 times dailyoffers effective relief.

For the management of erectile dysfunction, see section7.4.5.

6.1.6 Diagnostic andmonitoring devices fordiabetes mellitus

Blood monitoring

Blood glucose monitoring using a meter gives a directmeasure of the glucose concentration at the time of thetest and can detect hypoglycaemia as well as hyperglyc-aemia. Patients should be properly trained in the use ofblood glucose monitoring systems and to take appro-priate action on the results obtained. Inadequate under-standing of the normal fluctuations in blood glucose canlead to confusion and inappropriate action.

Patients using multiple injection regimens should under-stand how to adjust their insulin dose according to theircarbohydrate intake. With fixed-dose insulin regimens,the carbohydrate intake needs to be regulated, andshould be distributed throughout the day to match theinsulin regimen.

Self-monitoring of blood-glucose concentration isappropriate for patients with type 2 diabetes:

. who are treated with insulin;

. who are treated with oral hypoglycaemic drugs e.g.sulfonylureas, to provide information on hypoglyc-aemia;

. to monitor changes in blood-glucose concentrationresulting from changes in lifestyle or medication,and during intercurrent illness;

. to ensure safe blood-glucose concentration duringactivities, including driving.

Note In the UK blood-glucose concentration is expressed inmmol/litre and Diabetes UK advises that these units should beused for self-monitoring of blood glucose. In other Europeancountries units of mg/100 mL (or mg/dL) are commonly used.

It is advisable to check that the meter is pre-set in the correctunits.

If the patient is unwell and diabetic ketoacidosis issuspected, blood ketones should be measured accord-ing to local guidelines (section 6.1.3). Patients and theircarers should be trained in the use of blood ketonemonitoring systems and to take appropriate action onthe results obtained, including when to seek medicalattention.

Urinalysis

Tests for glucose range from reagent strips specific toglucose to reagent tablets which detect all reducingsugars. Few patients still use Clinitestc ; Clinistixc issuitable for screening purposes only. Tests for ketonesby patients are rarely required unless they becomeunwell—see also Blood Monitoring, above.

Microalbuminuria can be detected with Micral-TestIIcD but this should be followed by confirmation inthe laboratory, since false positive results are common.

GlucoseClinistixc (Bayer Diabetes Care)

Reagent strips, for detection of glucose in urine. Net price50-strip pack = £3.27

Clinitestc (Bayer Diabetes Care) D

Reagent tablets, for detection of glucose and other reducingsubstances in urine. Net price 36-tab pack = £2.00

Diabur-Test 5000c (Roche Diagnostics)


Diastixc (Bayer Diabetes Care)


Medi-Testc Glucose (BHR)


KetonesKetostixc (Bayer Diabetes Care)

Reagent strips, for detection of ketones in urine. Net price50-strip pack = £2.95

Ketur Testc (Roche Diagnostics)

Reagent strips, for detection of ketones in urine. Net price50-strip pack = £2.76

ProteinAlbustixc (Siemens)

Reagent strips, for detection of protein in urine. Net price50-strip pack = £4.10

Medi-Testc Protein 2 (BHR)

Reagent strips, for detection of protein in urine. Net price50-strip pack = £3.27

Other reagent strips available for urinalysisinclude:

Combur-3 Testc D (glucose and protein—Roche

Diagnostics), Clinitek MicroalbumincD (albumin and

creatinine—Siemens), Ketodiastixc D (glucose and

ketones—Bayer Diagnostics), Medi-Test Combi 2c D

(glucose and protein—BHR), Micral-Test IIc D

(albumin—Roche Diagnostics), MicroalbustixcD

(albumin and creatinine—Siemens), Uristixc D (glu-

cose and protein—Siemens)

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Meters and test strips

Meter (all D) Type ofmonitoring

Meterretail price

Compatibletest strips

Test stripnet price

Sensitivityrange(mmol/litre)

Manufacturer

Accu-Chekc Active1 Blood glucose Activec 50-strip pack= £15.16

0.6–33.3 RocheDiagnostics

Accu-Chekc

Advantage1Blood glucose Advantage Plusc 50-strip pack

= £15.170.6–33.3 Roche

Diagnostics

Accu-Chekc Aviva Blood glucose £12.99 Avivac 50-strip pack= £14.89


Accu-Chekc

Compact1Blood glucose Compactc 3 � 17-strip pack

= £15.290.6–33.3 Roche

Diagnostics

Accu-Chekc

Compact PlusBlood glucose £12.99 Compactc 3 � 17-strip pack

= £15.290.6–33.3 Roche

Diagnostics

Accu-Chekc Mobile Blood glucose £49.99 Mobilec 100 tests = £30.12 0.3–33.3 RocheDiagnostics

Accutrendc1 Blood glucose BM-Accutestc 50-strip pack= £14.31


Ascensia Breezec1 Blood glucose Ascensiac

Autodisc5 � 10-disc pack= £14.62

0.6–33.3 BayerDiabetesCare

Ascensia Espritc 21 Blood glucose Ascensiac

Autodisc5 � 10-disc pack= £14.62


Breeze 2c Blood glucose £14.34 Breeze 2c 5 � 10-disc pack= £14.34


CareSens Nc2 Blood glucose CareSens Nc 50-strip pack= £12.75

1.1–33.3 SpiritHealthcare

Contourc Blood glucose £10.80 ContourcFormerly Ascensiac

Microfill

50-strip pack= £14.74


FreeStylec1 Blood glucose FreeStylec 50-strip pack= £14.90

1.1–27.8 Abbott

FreeStyleFreedomc1

Blood glucose FreeStylec 50-strip pack= £14.90

1.1–27.8 Abbott

FreeStyle FreedomLitec

Blood glucose £11.49 FreeStyle Litec 50-strip pack= £14.90

1.1–27.8 Abbott

FreeStyle Litec Blood glucose £14.94 FreeStyle Litec 50-strip pack= £14.90

1.1–27.8 Abbott

FreeStyle Minic1 Blood glucose FreeStylec 50-strip pack= £14.90

1.1–27.8 Abbott

GlucoMenc Glyco1 Blood glucose GlucoMenc 50-strip pack= £13.67

1.1–33.3 MenariniDiagnostics

GlucoMenc GM Blood glucose £15.26 GlucoMen GMc 50-strip pack= £14.67


GlucoMenc LX Blood glucose £14.94 GlucoMenc LX 50-strip pack= £14.65


GlucoMenc PC1 Blood glucose GlucoMenc 50-strip pack= £13.67


GlucoMenc Visio Blood glucose £10.34 GlucoMenc VisioSensor



Glucotrendc1 Blood glucose Activec 50-strip pack= £14.76


One Touchc II1 Blood glucose One Touchc 50-strip pack= £14.59

1.1–33.3 LifeScan

One Touchc Basic1 Blood glucose One Touchc 50-strip pack= £14.59

1.1–33.3 LifeScan

1. Meter no longer available2. Free of charge from diabetes healthcare professionals

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Oral glucose tolerance test

The oral glucose tolerance test is used mainly fordiagnosis of impaired glucose tolerance; it is not recom-mended or necessary for routine diagnostic use whensevere symptoms of hyperglycaemia are present. Inpatients who have less severe symptoms and bloodglucose levels that do not establish or exclude diabetes(e.g. impaired fasting glycaemia), an oral glucose toler-ance test may be required. It is also used to establish thepresence of gestational diabetes. The oral glucose tol-erance test generally involves giving anhydrous glucose75 g (equivalent to Glucose BP 82.5 g) by mouth to thefasting patient, and measuring blood-glucose concen-trations at intervals.

The appropriate amount of glucose should be given with200–300 mL fluid. Anhydrous glucose 75 g may alter-natively be given as 113 mL Polycalc (Nutricia Clinical)with extra fluid to administer a total volume of 200–300 mL.

6.2 Thyroid and antithyroiddrugs

6.2.1 Thyroid hormones

6.2.2 Antithyroid drugs

6.2.1 Thyroid hormones

Thyroid hormones are used in hypothyroidism (myx-oedema), and also in diffuse non-toxic goitre, Hashimo-to’s thyroiditis (lymphadenoid goitre), and thyroid carci-noma. Neonatal hypothyroidism requires prompttreatment for normal development. Levothyroxinesodium (thyroxine sodium) is the treatment of choicefor maintenance therapy.

In infants and children with congenital hypothyroidismand juvenile myxoedema, the dose of levothyroxineshould be titrated according to clinical response, growthassessment, and measurements of plasma thyroxine andthyroid-stimulating hormone. See BNF for Children(section 6.2.1) for suitable dosage regimens.

Meter (all D) Type ofmonitoring

Meterretail price

Compatibletest strips

Test stripnet price

Sensitivityrange(mmol/litre)

Manufacturer

One Touchc Profile1 Blood glucose One Touchc 50-strip pack= £14.59

1.1–33.3 LifeScan

One Touch Ultrac1 Blood glucose One Touch Ultrac 50-strip pack= £14.75

1.1–33.3 LifeScan

One Touch Ultra 2c Blood glucose £25.98 One Touch Ultrac 50-strip pack= £14.75

1.1–33.3 LifeScan

One TouchUltraEasyc

Blood glucose £25.98 One Touch Ultrac 50-strip pack= £14.75

1.1–33.3 LifeScan

One TouchUltraSmartc2

Blood glucose One Touch Ultrac 50-strip pack= £14.75

1.1–33.3 LifeScan

One Touchc Vita2 Blood glucose One Touchc Vita 50-strip pack= £14.81

1.1–33.3 LifeScan

Optiumc1 Blood ketones Optiumc bb-ketone 10-strip pack= £19.92

0–8.0 Abbott

Optium Xceedc Blood glucose £17.24 OptiumPluscFormerly Med-isensec Optium Plus


1.1–27.8 Abbott

Blood ketones Optiumc bb-ketone 10-strip pack= £19.55

0–8.0 Abbott

PocketScanc1 Blood glucose PocketScanc 50-strip pack= £14.41

1.1–33.3 LifeScan

Prestigec Blood glucose £8.62 Prestigec 50-strip pack= £14.51

1.4–33.3 HomeDiagnostics

TRUEonec Blood glucose n/a All-in-one teststrips and meter

50-strip pack withmeter = £14.36


TRUEresultc2 Blood glucose £11.74 TRUEresultc2 50-strip pack= £14.36


TRUEresult twistc2 Blood glucose £11.74 TRUEresultc 50-strip pack= £14.36


TRUEtrackc Blood glucose £8.62 TRUEtrackc 50-strip pack= £14.25


WaveSense Jazzc Blood glucose £24.99 WaveSense Jazzc 50-strip pack= £14.45

1.1–33.3 WaveSense

1. Meter no longer available2. Free of charge from diabetes healthcare professionals

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Ttt of diabetes (bnf may 2012)

Health & Medicine

Transcript of Ttt of diabetes (bnf may 2012)