3_1 Blood Glucose-lowering Medicines

7/30/2019 3_1 Blood Glucose-lowering Medicines

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Slides current until 2008

Pharmacological management

Blood glucose-lowering medicines

Section 3 | Part 1 of 3

Curriculum Module III-2 | Glucose-lowering medication


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Blood glucose-lowering medicinesCurriculum Module III-2

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Aims of treatment

Reduce the symptoms ofhyperglycaemia

Limit adverse effects of treatment

Maintain quality of life andpsychological well-being

Prevent or delay vascularcomplications of diabetes


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UKPDS:long-term glucose control

06

7

8

9

0 3 6 9 12 15

HbA1c

(%

)

Years of treatment

Conventional

Intensive

UKPDS Study Group 1998


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Natural history of type 2 diabetes

Normal Impaired glucose

tolerance

Type 2 diabetes

Time

Insulin

resistance

Insulin

production

Glucose

level

Beta-cell

dysfunction

Henry 1998


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Mechanisms of action

Insulin secretagogues: sulphonylureasand meglitinides increase insulinproduction

Biguanides and thiazolidinedionesreduce glucose production

Thiazolidinediones and biguanides reduceinsulin resistance

Alpha-glucosidaseinhibitors slowabsorption of sucroseand starch

GLP-1 (incretins)improve response toglucose level


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Understanding the names

Chemical name relates tochemical structure

Generic name identifies a uniquecompound with therapeuticproperties

Brand name given by themanufacturer


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Blood glucose-lowering medicinesCurriculum Module IV-1

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What are the most common oralblood glucose-lowering

medicines in your community?

What are their brand names andgeneric names?


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The principles of combinationtherapy

Two (or more) oral blood glucose-lowering medicines that have

different mechanisms of action

Two medications rather thanincrease in initial medicine to

maximum dosage Fewer side effects than mono-

therapy at higher doses


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Expected effect of bloodglucose-lowering medicines

Class of medicine Expected decrease inHbA1C in mono-therapy

Alpha-glucosidaseinhibitor

0.5-0.8%

Biguanide

Insulin sensitisersMost insulinsecretagogues

Nateglinide

1.0-1.5%

1.0-1.5%

1.0-1.5%

0.5%

Canadian Diabetes Association 2003


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Strategies to help people remember

Check that people understandhow and when to take their

medicines Clarify the benefits of treatment

Keep regimens simple

Minimize costs

Discuss adverse effects

Rubin 2005


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HbA1C Pre-meal 2 hourspost-meal

Target for people

who can achieve it(without too muchhypoglycemia)1

< 6% 4-6 mmol/L 5-8 mmol/L

Target for mostpeople withdiabetes


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Suggested starting medicine

HbA1c BMI Suggested medicine

25 Biguanide alone or in combination

9% 2 medicines from different classes

or insulin

CDA 2003


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Increasing or adding

If goals have not been reachedwithin 2-3 months, medication

should be increased or medicationfrom a different class added

Target levels should be reachedwithin 6 months

Insulin should be added ifnecessary to reach target levels


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Biguanides

Action not fully understood

Decreases glucose production inliver

Mild and variable effect onmuscle sensitivity to insulin

Side effects

Gastrointestinal (nausea,abdominal discomfort or diarrheaand occasional constipation)

Lactic acidosis


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Biguanides

Contraindications

Renal insufficiency

Liver failure

Heart failure Severe gastrointestinal disease

Advantages

Do not cause hypoglycaemiawhen used as mono-therapy

Do not cause weight gain; may

contribute to weight loss


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Biguanides

First-line treatment inoverweight or obese people

Do not cause weight gain

Have some effect onresistance at the periphery


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Biguanides

Caution

Should be discontinued 24 hours

before procedures requiringintravenous contrast dye

Can be restarted 48 hours after

the procedure if renal function isnot compromised


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Sulphonylureas

Increase insulin secretion regardless ofblood glucose levels

Many different medicines in this class

Side effects

Hypoglycaemia

Stimulate appetite and provoke weightgain

Nausea, fullness, heartburn

Occasional rash

Swelling


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Sulphonylureas

Short-acting secretagogues

Meglitinides increase insulin

secretion in response to increasingblood glucose levels (i.e. aftereating)

Side effects Hypoglycaemia (probably lessthan sulphonylureas)

Weight gain


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Sulphonylureas

Contraindications

Type 1 diabetes

Pregnancy Breastfeeding

Sulphonylureas - Use cautiouslywith liver or kidney disease

Meglitinides - Severe impairment ofliver function

l d l l d


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Sulphonylureas

Things to remember

Some sulphonylureas have sloweronset and lower peak than glyburide,

thus may provoke less hypoglycaemia

Some need to be taken only once aday, therefore may be easier toremember to take

First generation sulphonylureas, suchas chlorpropamide may accumulateand cause hypoglycaemia due to theirlong duration of action

Bl d l l i di i


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Thiazolidinediones

Improve sensitivity to insulin in muscle,adipose tissue and liver

Reduce glucose output from liver

Changes fat distribution by decreasingvisceral fat and increasing peripheral fat

Side effects

Weight gain, fluid retention Upper respiratory infection and

headache

Decrease in haemoglobin

Bl d l l i di i


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ThiazolidinedionesContraindications

Liver disease, heart failure orhistory of heart disease

Pregnancy and breast feeding

They are not contraindicated inrenal insufficiency

Potential benefits

Reduced levels of LDL-cholesterol and increased level

of HDL-cholesterol

Bl d l l i di i


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Alpha glucosidase inhibitors

Slow digestion of sucrose and starchand therefore delay absorption

Slow post-meal rise in blood glucose

Side effects

Flatulence, abdominal discomfort ,diarrhoea

As mono-therapy will notcausehypoglycaemia

Hypoglycaemia when used with othermedicine (e.g. a sulphonylurea)

Bl d l l i di i


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Alpha glucosidase inhibitors

Contraindications

Intestinal diseases, such as

Crohns Autonomic neuropathy

affecting the gastro-intestinaltract

Must be taken just before ameal

Bl d l l i di i


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GLP-1 (incretin mimetic agent)

Improves beta-cell responsiveness toincreasing glucose levels

Decreases glucagon secretion Slows gastric emptying Results in a feeling of fullness Must be injected subcutaneously twice a

day, within 30-60 minutes before a meal Reduces HbA1c by ~1%

Side effects Nausea Weight loss Diarrhoea Risk of hypoglycaemia when used with a

sulphonylurea

Blood glucose lowering medicines


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GLP-1 (incretin mimetic agent)

Contraindications

End-stage kidney disease or

renal impairment Pregnancy

Severe gastrointestinal disease



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Older people with diabetes

Beware of the possible reductions in General good health (with other

concomitant conditions)

Kidney function (and increased risk of

hypoglycaemia) Family support and monitoring

Vision

Flexibility and activities of daily living

Remember also

Poly-pharmacy increases the risk ofmedicine-related adverse events

To review all medication and

complementary therapies



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Always start with the lowest doseof any blood glucose-lowering

medicine and increase gradually Using shorter-acting medicines

reduces the risk of hypoglycaemia

Hypoglycaemia may increase therisk of falls and heart attack inolder people



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Remember the possibility of

Forgetfulness

Poor motivation

Depression

Cognitive deficits

Poly-pharmacy

Reduced manual dexterity

These impact on the ability to maintainself-care and achieve maximum benefitsfrom blood glucose-lowering medicines.



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Ineffectiveness of blood glucose-lowering medicines

If oral blood glucose-loweringmedicines are ineffective

Check diet and exercise Consider adding intermediate orlong-acting insulin at bedtime

Maintain metformin Consider reducing or stoppingthe morning sulphonylurea



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Class of medicine Likely to causeweight gain

Likely to causehypoglycaemia

Target post-meal glucose

Sulphonylureas

Biguanide

Glitazones

Meglitinides

Alpha-glucosidaseinhibitors

Incretin mimeticagent



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Case study

AB has had type 2 diabetes for two years

51-year-old truck driver

BMI of 32, blood pressure at 150/95

HbA1C 9.5% No medication

AB says he has no time for exercise andwill not change his meal pattern

What medication do you think should bestarted and why?



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Summary

Lifestyle changes first

Start medicine as soon asneeded

Add a different kind

No delay starting insulin



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Blood glucose lowering medicinesCurriculum Module III-2

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Review question

1. Which of the following adversereactions are most likely due tometformin therapy?

a. Oedema

b.Diarrhea

c. Heart failure

d.Weight gain



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Review question

2. Which of the following statementsbest describes alpha-glucosidaseinhibitors?

a. Likely to cause weight gain

b. Should be taken with first bite ofthe meal

c. Commonly associated withhypoglycaemia

d. Well tolerated, few side effects



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Review question

3. Which statement is FALSE?

a. All oral medicines used to treat diabetesshould be discontinued once insulin is

startedb. In most people, blood glucose-lowering

medicines become less effective over time

c. Blood glucose-lowering medicines fromdifferent classes are often used incombination to reach target blood glucose

d. It is important to be physically active andfollow a prescribed meal plan in addition toblood glucose-lowering medicines



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Review question

JL is a 45-year-old man. He has been taking5 mg glyburide and 500 mg metformin atbreakfast and supper. His fasting bloodglucose ranges from 5.36.7mmol/L but he

has been experiencing hypoglycaemia mostdays at 3 or 4 pm.

4. What is the likely cause of JLs low bloodsugars?

a. Breakfast metformin

b. Supper metformin

c. Breakfast glyburide

d. Supper glyburide



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Review question

5. When filling his prescription for asulphonylurea, what is the mostimportant thing to discuss with John?

a. What and when to eat

b. When to take the medication

c. How to recognize and treat

hypoglycaemiad. When to see his doctor again



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Answers

1. b

2. b

3. a

4. c

5. c



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References

1. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood glucose control withsulphonylureas or insulin compared with conventional treatment and risk ofcomplications in person with diabetes with type 2 diabetes (UKPDS 33). Lancet 1998;352: 837-53.

2. Ahmann AJ, Riddle MC. Current blood glucose lowering medicines for type 2 diabetes.Postgrad Med 2002; 111(5): 32-46.

3. Henry RR. Type 2 diabetes care: the role of insulin-sensitizing agents and practicalimplications for cardiovascular disease prevention. Am J Med 1998; 105(1A): 20S-26S.

4. Luna B, Feinglos MN. Blood glucose-lowering medicines in the management of type 2diabetes mellitus. Am Fam Physician2001; 63(9): 1747-56.

5. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. ClinicalPractice Guidelines for the Prevention and Management of Diabetes in Canada. Can JDiab 2003; 27(supple 2).

6. Yki-Jarvinnen H, Ryysy L, Nikkila K, et al. Comparison of bedtime insulin regimen inperson with diabetes with type 2 diabetes mellitus; a randomized control trial. AnnalsIntern Med1999; 130(5): 89-96.

7. Amylin Pharmaceuticals Inc and Eli Lilly & Co. Byetta (cited 2005July 25) (16 screens).(Available from: http://www.byetta.com)

8. Rubin Rr. Adherence to pharmacologic therapy in patients with type 2 diabetesmellitus. Am J Med 2005; 118(5A): 275-345.

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