Med scape April2015

MED SCAPE AND ETC.Chonpiti Siriwan, MD.

April 2015.

Topic

• Endocrine society guideline for primary aldosteronism

2015

• NBHA Diagnostic criteria for osteoporosis: PROs and

Cons?

• AACE and ACE Clinical Practice Guidelines for

Developing a Diabetes Mellitus Comprehensive Care Plan

2015

Topic

• Increased Stroke Risk in Some Patients With Subclinical

Hypothyroidism

• FDA Panel Backs New Safety Warnings on Two Diabetes

Drugs

• Statins for Primary Prevention in Everyone 75 Years and

Older? It Could Be Cost-Effective: Analysis

GUIDELINES ON

PRIMARY

ALDOSTERONISMTitle:

The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline

March 20, 2015

DO NOT DISTRIBUTE. DRAFT: CONFIDENTIAL. DO NOT DISTRIBUTE.

Guidelines on Primary Aldosteronism

Authors

• John W. Funder (chair)

• Robert M. Carey

• Franco Mantero

• Mohammad Hassan

Murad

• Martin Reincke

• Hirotaka Shibata

• Michael Stowasser

• William F. Young. Jr.

Cosponsoring Associations

• European Society of

Endocrinology

• European Society of

Hypertension

• International Society of

Endocrinology

• International Society of

Hypertension

• The Japanese Society of

Hypertension

Summary of recommendations

• Case detections• Hypertension

• Sustain BP ≥ 180/110 mmHg

• Resistance HTN (on 3 conventional antihypertensive drugs, including a diuretic)

• BP <140/90: On ≥4 antihypertensive drugs

• HTN and spontaneous or diuretic induced hypokalemia

• HTN and adrenal incidentaloma

• HTN and a family history

• Early onset hypertension or cerebrovascular accident at a young age (<40 years)

• All first degree relatives of patients with PA

• Sustained BP >150/100

• Patients with hypertension (BP>140/90) and obstructive sleep apnea.

Groups With High Prevalence of PA

Patient group Prevalence

• Moderate/severe hypertension

• Classification of BP based on JNC

6th

Overall: 6.1%

Stage 1 (mild): 2%

Stage 2 (moderate): 8%

Stage 3 (severe): 13%

Resistant hypertension( even on >3

hypertensive medications)

17%–23%

Hypertensive patients with

spontaneous or diuretic-induced PA

hypokalemia

Specific prevalence figures are not

available, but more frequently found in

this group.

Hypertension with adrenal

incidentaloma

Median: 2% (range, 1.1%–10%)

Hypertension with obstructive sleep

apnea

34%, among newly hypertensive

patients referred to a tertiary referral

center and found to have obstructive

sleep apnea

Algorithm for the detection, confirmation,

subtype testing, and treatment of primary

aldosteronism (PA)

Case detections

• Use of the plasma aldosterone/renin ratio (ARR) to detect

possible cases of PA in these patient groups

• ARR:

• Detection test only

• Repeat if inconclusive result

Factors That May Lead to False-Positive

or False-Negative ARR Results

Remarks

• Renin inhibitors

• Lower PRA

• But raise DRC.

• Expected to result

• false positive ARR levels for renin measured as PRA

• false negatives for renin measured as DRC

• In premenopausal women

• Briskly raising plasma aldosterone level in the luteal phase

• False positives can occur during the luteal phase

Measurement of ARR: A Suggested Approach

• Correct hypokalemia

• Use syringe and needle [preferably not a Vacutainer® to minimize the risk of spuriously raising potassium]

• Waiting at least 5 seconds after tourniquet release (if used)

• Encourage patient to liberalize (rather than restrict) sodium intake.

• Withdraw agents that markedly affect the ARR (Mulatero, Hypertension, 2002) for at least 4 weeks: • Spironolactone, eplerenone, amiloride, and triamterene

• Potassium-wasting diuretics

• Products derived from liquorice root (e.g., confectionary licorice, chewing tobacco)

Measurement of ARR: A Suggested Approach

• Withdraw other medications that may affect the ARR for at

least 2 weeks:

• Beta-adrenergic blockers, central alpha-2 agonists (e.g., clonidine,

alpha- methyldopa), nonsteroidal anti-inflammatory drugs

• Angiotensin-converting enzyme inhibitors, angiotensin receptor

blockers, renin inhibitors, dihydropyridine calcium channel

antagonists

• Controlled BP with relatively noninterfering medications

• Establish OC and HRT status

• Estrogen-containing medications may lower DRC

• Cause false-positive ARR when DRC

• Do not withdraw OC unless confident of alternative effective

contraception.

Medications With Minimal Effects on

Plasma Aldosterone Levels

Conditions for collection of blood

• Midmorning

• after the patient has been up (sitting, standing, or walking)

for at least 2

• Seated for 5-15 min before blood collection

• Avoiding stasis and hemolysis

• Maintain sample at room temperature (and not on ice, as

this will promote conversion of inactive to active renin)

during delivery to laboratory and prior to centrifugation

and rapid freezing of plasma component pending assay

Case confirmations

• Positive aldosterone-renin ratio (ARR)

• One or more confirmatory tests to definitively confirm or

exclude the diagnosis

• Setting may NO NEED confirmation test

• spontaneous hypokalemia

• undetectable renin

• plasma aldosterone concentration (PAC) >20 ng/dl,

Confirmation test

• Oral sodium loading test

• Saline infusion test

• In a modified approach which appears, in preliminary studies, to

have much higher sensitivity for diagnosing PA, patients remain in

a seated position for at least 30 mins and during the infusion

(Amhed, 2014).

• Fludrocortisone suppression test

• Captopril challenge test

Subtype classification

• CT: initial study in subtype testing

• Large masses: ACC (Almost always >4 cm)

• APA: small hypodense nodules (usually <2 cm in diameter)

• IAH: normal adrenal glands or show nodular changes

• CT limitations

• Small APA

• Older patient (>35 years): nonfunctioning unilateral adrenal

macroadenomas are not uncommon

• No advantage of MRI over CT in subtype evaluation

AVS: subtype classification

• Experienced radiologist

• Distinction between unilateral and bilateral adrenal

disease

• Surgery desired patients

• AVS may not be needed • younger patients (< age 35)

• spontaneous hypokalemia

• marked aldosterone excess

• unilateral cortical adenoma on adrenal CT scan

AVS

• Advocate the use of continuous cosyntropin infusion

during AVS

• 50 μg/hour

• 30 minutes before adrenal vein catheterization and

continued throughout the procedure

• “Cortisol-corrected aldosterone ratios”

• Cutoff ratio from high-side to low- side > 4:1

Other modalities for subtype classification

• Iodocholesterol scintigraphy. [131I]-19-iodocholesterol

scintigraphy

• Sensitivity depend on size of adenoma

• Not helpful in small adenoma (<1.5cm)

• 18-Hydroxycorticosterone Levels (18-OHB)

• >100 ng/dl at 8:00 a.m in APA

• No support evidence

• (11)C-Metomidate Positron Emission Tomography (PET)-

CT

• 87% specificity and 76% sensitivity for APA

• Future use

Genetic testing

• Indication for FH-I genetic testing

• Onset of confirmed PA <20 years of age

• Family history of PA or of strokes at young age (<40 years)

• Testing for germline mutations in KCNJ5

• Causing FH-III

• Very young patients with PA

Testing for Familial Forms of PA: FH-I [GRA]

• AD, 1% cause of PA

• CYP11B1/CYP11B2 chimeric gene

• Aldosterone secretion depend on ACTH

• Indicated in family history of PA or of strokes at a young

age (<40years)

Testing for Familial Forms of PA: FH-II

• AD, possibly genetically heterogeneous

• No response to DEX suppression

• Negative for GRA mutation

• 7% of PA

• Presented with APA or IHA

• Unclear molecular basis

• Abnormal chromosomal region 7p22 in several linkage

analysis

• Somatic KCNJ5 mutations (~FH-III) in some cases

Testing for Familial Forms of PA: FH-III

• Mutation in the KCNJ5 gene

• Encoding the potassium channel Kir 3.4

• 9 of 10 affected subjects were diagnosed at age 6 or

younger

Mulatero, P. et al. (2012) Role of KCNJ5 in familial and sporadic primary aldosteronism

Nat. Rev. Endocrinol. doi:10.1038/nrendo.2012.230

Genetic Events in Sporadic APA

• KCNJ5

• ATP1A1 and ATP2B3

• ATP1A1: coding for the α subunit of the Na+,K+-ATPase

• ATP2B3: coding for the plasma membrane calcium-transporting

ATPase 3 (PMCA3)

• Significantly reduced Na+,K+-pump activity

• Mutation carriers show increased plasma aldosterone and lower

potassium compared with non-carriers

• More common in males

Genetic Events in Sporadic APA

• CACNA1D

• Encoding a voltage-gated calcium channel

• 5-11% in zona glomerulosa–like APAs without KCNJ5

mutations

• Activation of Cav1.3 channels

• Increases intracellular Ca2+ entry leading to Ca2+-

mediated signaling and enhanced aldosterone secretion

Treatment

• Unilateral laparoscopic adrenalectomy

• unilateral PA i.e., aldosterone-producing adenoma [APA]

• unilateral adrenal hyperplasia [UAH]

• Medical treatment including a mineralocorticoid receptor

(MR) antagonist

• Unable to surgery

• Unwilling to surgery

• Unwilling or unable to undergo further investigations

Treatment

• For medical treatment

• Suggest spironolactone as the primary agent

• Eplerenone as an alternative

• For GRA

• Lowest dose of glucocorticoid to lower corticotropin (ACTH)

• Normalize blood pressure and serum potassium levels rather than

first-line treatment with an MR antagonist

NBHA DIAGNOSTIC CRITERIA FOR

OSTEOPOROSIS: PROS AND CONS?

• Pros: Alexandra PapaioannouDivision of Geriatric Medicine, McMaster University, St Peter's

Hospital, GERAS Centre, Hamilton, ON L8M 1W9, Canada

• Cons: John T SchousboePark Nicollet Health Services, Minneapolis, MN 55416, USA

Lancet Diabetes Endocrinol 2015; 3: 234–37.

Position paper

Osteoporos Int (2014) 25:1439–1443.

DOI 10.1007/s00198-014-2655-z

National Bone Health Alliance Working Group

• Group of 17 clinicians and clinical scientists

• National Osteoporosis Foundation (NOF)

• American Society for Bone and Mineral Research (ASBMR)

• American Academy of Orthopedic Surgeons

• Centers for Disease Control

Fracture types that allow a diagnosis of

osteoporosis • With or without BMD test: Low-trauma hip fracture

• Osteopenia: Low-trauma clinical vertebral fracture,

proximal humerus fracture, or pelvis fracture

• Clinician reason: Incidental finding of a vertebral fracture

on a radiograph (a morphometric vertebral fracture)

• Osteopenia at the lumbar spine or hip by BMD: low-

trauma distal forearm fracture

Role of FRAX in making the diagnosis of

osteoporosis

• WHO fracture risk assessment tool

• Combine femoral neck BMD (or total hip)

• Well-validated and weighted clinical risk factors for

fracture

• Largely independent of BMD

• Useful as risk predicting

• hip fracture

• major osteoporotic fractures

Role of FRAX in making the diagnosis of

osteoporosis • Dx osteoporosis

• 10-year probability of hip fracture is ≥3 %

• 10-year probability of major osteoporotic fracture is ≥20 %

• Reflect treatment intervention thresholds in the USA

• Described in the NOF Clinician’s Guide

• Cost-effectiveness criteria for hip fracture management

• Logical basis for making a diagnosis of osteoporosis

Further considerations

• Identifying greater number of people elevated risk for

fracture

• Increasing awareness

• Encouraging strategies to lower risk

• Pharmacologic and non-pharmacologic

• FRAX as the outcome of clinical study

Conclusion

• Dx osteoporosis

• Postmenopausal women

• Men > 50 years

• Elevated risk for future fractures based on FRAX

• T-score of ≤−2.5 at the spine or hip

• Low-trauma hip fracture

• Low-trauma vertebral, proximal humerus, pelvis,

• Some cases of distal forearm fracture

Conclusion

• Osteoporotic associated fracture

• 2/3 Hip, vertebral, distal radius, and pelvis

• Major osteoporotic fractures

• Proximal humerus

• Hip

• Spine

• Distal forearm

PROs:(1)

• 2-paradigm shifts in the diagnosis and management of

osteoporosis

• Clinical risk factors: fracture risk prediction: FRAX

• Importance of bone quality

• Fracture prediction: NOT base on BMD only

• More than half of fractures occur in the non-osteoporotic

range

• Indicating relatively poor sensitivity of BMD

• FIT trial: bisphosphonates decreased vertebral fracture

risk in patients with low bone mass (Femoral neck T

scores 1.6-2.5)

Mayo Clin Proc, 80 (2005), pp. 343–349.

PROs: (2)

• Clinical predictors of fracture have powerful case- finding

potential, particularly when used in older individuals

• FRAX alone comparable predictive ability as FRAX with

BMD and identifies patients at risk who are responsive to

pharmaceutical intervention

• BMD measurement is not possible?

• Bed ridden patients

• More severe underlying disease: more absolute risk

reduction

• Previous fracture is a powerful predictor of a future

fracture

Cons: (1)

• For expanded definition

• Increase the proportion of US adults aged > 65 years who

dx osteoporosis

• 40% -> 72% of women

• 7% -> 34% of men

• Higher demands on the health-care system

• Benefits or harm?: broadening diagnostic criteria

Cons (2)

• Pivotal trials of alendronate, risedronate, and denosumab

• Efficacy only in • Women with a BMD T-score < −2·5

• Existing vertebral fractures

• No efficacy • BMD T-score > −2·5

• no prevalent vertebral fracture

• Clodronate• reduced clinical fractures

• older women not selected on the basis of BMD

• But fracture benefit in women with neither a traditional diagnosis of osteoporosis (based on T score) nor the presence of radiographic vertebral fracture.

Ann Intern Med, 148 (2008), pp. 197–213

J Bone Miner Res, 27 (2012), pp. 211–218

J Bone Miner Res, 22 (2007), pp. 135–141

Cons (3)

• Low evidence of benefit of anti-osteoporotic medication in

patient with BMD T-scores > −2.5

• Fracture risk driven mainly by other skeletal factors

• bone type 1 collagen

• hydroxyapatite crystal structure

• bone microarchitecture

• non-skeletal factors: fall propensity

• Lack evidence of impaired bone quality or fracture risk by

current medication

Con(4)

• Only 1-cost-effective study was used in FRAX

• Generalize to other situation?

• Increase primary care workload

• Psychological impact

• Need further evidence-based research

• Measureable characteristics of bone that contribute to

fracture risk, other than BMD, such as deficits in bone

geometry, microstructure, or material properties

Osteoporos Int, 19 (2008), pp. 437–447.

AACE AND ACE CLINICAL PRACTICE

GUIDELINES FOR DEVELOPING A DIABETES

MELLITUS COMPREHENSIVE CARE PLAN

ENDOCRINE PRACTICE Vol 21 No. 4 April 2015

Writing Committee Cochairpersons

Yehuda Handelsman MD, FACP, FACE, FNLA

Zachary T. Bloomgarden, MD, MACE

George Grunberger, MD, FACP, FACE

Guillermo Umpierrez, MD, FACP, FACE

Robert S. Zimmerman, MD, FACE

CPG Objectives and Structure

• An evidence-based education resource

• Easy-to-follow structure

• 24 diabetes management questions

• 67 practical recommendations

• Concise, practical format that complements existing DM

textbooks

• Suitable for electronic implementation to assist with

clinical decision-making for patients with DM

AACE DM CPG Questions

1. How is diabetes screened and

diagnosed?

2. How is prediabetes managed?

3. What are glycemic treatment goals of

DM?

4. How are glycemic targets achieved for

T2D?

5. How should glycemia in T1D be

managed?

6. How is hypoglycemia managed?

7. How is hypertension managed in

patients with diabetes?

8. How is dyslipidemia managed in


9. How is nephropathy managed in


10. How is retinopathy managed in


11. How is neuropathy diagnosed and

managed in patients with diabetes?

12. How is CVD managed in patients with

diabetes?

13. How is obesity managed in patients

with diabetes?

AACE DM CPG Questions

14. What is the role of sleep medicine in

the care of the patient with diabetes?

15. How is diabetes managed in the

hospital?

16. How is a comprehensive diabetes care

plan established in children and

adolescents?

17. How should diabetes in pregnancy be

managed?

18. When and how should glucose

monitoring be used?

19. When and how should insulin pump

therapy be used?

20. What is the imperative for education

and team approach in DM

management?

21. What vaccinations should be given to


22. How should depression be managed in

the context of diabetes?

23. What is the association between

diabetes and cancer?

24. Which occupations have specific

diabetes management requirements?

• Age ≥45 years without other risk factors

• Family history of T2D

• CVD

• Overweight

• BMI ≥30 kg/m2

• BMI 25-29.9 kg/m2 plus other risk

factors*

• Sedentary lifestyle

• Member of an at-risk racial or ethnic group:

Asian, African American, Hispanic, Native

American, and Pacific Islander

• Dyslipidemia

• HDL-C <35 mg/dL

• Triglycerides >250 mg/dL

• IGT, IFG, and/or metabolic syndrome

• PCOS, acanthosis nigricans, NAFLD

• Hypertension (BP >140/90 mm Hg or therapy

for hypertension)

• History of gestational diabetes or delivery of

a baby weighing more than 4 kg (9 lb)

• Antipsychotic therapy for schizophrenia

and/or severe bipolar disease

• Chronic glucocorticoid exposure

• Sleep disorders† in the presence of glucose

intolerance

• Screen at-risk individuals with glucose values in the normal range every 3 years

• Consider annual screening for patients with 2 or more risk factors

Criteria for Screening for T2D and Prediabetes

in Asymptomatic Adults

55

*At-risk BMI may be lower in some ethnic groups; consider using waist circumference.†Obstructive sleep apnea, chronic sleep deprivation, and night shift occupations.

BMI = body mass index; BP = blood pressure; CVD=cardiovascular disease; HDL-C = high density lipoprotein cholesterol; IFG =

impaired fasting glucose; IGT = impaired glucose tolerance; NAFLD = nonalcoholic fatty liver disease; PCOS = polycystic ovary

syndrome; T2D, type 2 diabetes.

Q1. How is diabetes screened and diagnosed?

Diagnostic Criteria for Prediabetes and

Diabetes in Nonpregnant Adults

56

Normal High Risk for Diabetes Diabetes

FPG <100 mg/dLIFG

FPG ≥100-125 mg/dLFPG ≥126 mg/dL

2-h PG <140 mg/dLIGT

2-h PG ≥140-199 mg/dL

2-h PG ≥200 mg/dL

Random PG ≥200 mg/dL +

symptoms*

A1C <5.5%5.5 to 6.4%

For screening of prediabetes†

≥6.5%

Secondary‡

*Polydipsia (frequent thirst), polyuria (frequent urination), polyphagia (extreme hunger),

blurred vision, weakness, unexplained weight loss.

†A1C should be used only for screening prediabetes. The diagnosis of prediabetes, which

may manifest as either IFG or IGT, should be confirmed with glucose testing.

‡Glucose criteria are preferred for the diagnosis of DM. In all cases, the diagnosis should

be confirmed on a separate day by repeating the glucose or A1C testing. When A1C is

used for diagnosis, follow-up glucose testing should be done when possible to help

manage DM.

FPG, fasting plasma glucose; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; PG, plasma glucose.

Q1. How is diabetes screened and diagnosed?

AACE Recommendations for A1C Testing

• A1C should be considered an additional optional

diagnostic criterion, not the primary criterion for diagnosis

of diabetes

• When feasible, AACE/ACE suggest using traditional

glucose criteria for diagnosis of diabetes

• A1C is not recommended for diagnosing type 1 diabetes

• A1C is not recommended for diagnosing gestational

diabetes

AACE Recommendations for A1C Testing

• A1C levels may be misleading in several ethnic

populations (for example, African Americans)

• A1C may be misleading in some clinical settings

• Hemoglobinopathies

• Iron deficiency

• Hemolytic anemias

• Thalassemias

• Spherocytosis

• Severe hepatic or renal disease

• AACE/ACE endorse the use of only standardized,

validated assays for A1C testing

Management of prediabetes

• IFG

• IGT

• Metabolic syndrome

• Frequent measurement of FPG and/or an OGTT

• Manage CVD risk factors (especially elevated blood

pressure and/or dyslipidemia) and excessive weight, and

monitor these risks at regular intervals

• Attempts to lose 5 to 10% of body weight

• Moderate physical activity (e.g., walking) at least 150

minutes per week

Medical and Surgical Interventions Shown to

Delay or Prevent T2D

62

T2D, type 2 diabetes.

1. DPP Research Group. N Engl J Med. 2002;346:393-403. 2. STOP-NIDDM Trial Research Group. Lancet. 2002;359:2072-2077.

3. Defronzo RA, et al. N Engl J Med. 2011;364:1104-15. 4. DREAM Trial Investigators. Lancet. 2006;368:1096-1105.

5. Torgerson JS, et al. Diabetes Care. 2004;27:155-161. 6. Garvey WT, et al. Diabetes Care. 2014;37:912-921.

7. Sjostrom L, et al. N Engl J Med. 2004;351:2683-2693.

Q2. How is prediabetes managed?

Intervention Follow-up Period

Reduction in Risk of T2D

(P value vs placebo)

Antihyperglycemic agents

Metformin1 2.8 years 31% (P<0.001)

Acarbose2 3.3 years 25% (P=0.0015)

Pioglitazone3 2.4 years 72% (P<0.001)

Rosiglitazone4 3.0 years 60% (P<0.0001)

Weight loss interventions

Orlistat5 4 years 37% (P=0.0032)

Phentermine/topiramate6 2 years 79% (P<0.05)

Bariatric surgery7 10 years 75% (P<0.001)

Lifestyle modification should be used with all pharmacologic or surgical interventions.

Outpatient Glucose Targets for Nonpregnant Adults

Parameter Treatment Goal

A1C, %

Individualize on the basis of age, comorbidities,

duration of disease, and hypoglycemia risk:

• In general, ≤6.5 for most*

• Closer to normal for healthy

• Less stringent for “less healthy”

FPG, mg/dL <110

2-Hour PPG, mg/dL <140

63Q3. What are glycemic treatment goals of DM?

FPG = fasting plasma glucose; PPG = postprandial glucose.

*Provided target can be safely achieved.

Less stringent glucose goal

• A1C: 7-8%

• Patients with history of severe hypoglycemia, limited life

expectancy, advanced renal disease or macrovascular

complications, extensive comorbid conditions, or long-

standing DM in which the A1C goal has been difficult to

attain despite intensive efforts

• So long as the patient remains free of polydipsia, polyuria,

polyphagia, and other hyperglycemia- associated

symptoms

Inpatient Glucose Targets for

Nonpregnant Adults

Hospital Unit Treatment Goal

Intensive/critical care

Glucose range, mg/dL 140-180*

General medicine and surgery, non-ICU

Premeal glucose, mg/dL <140*

Random glucose, mg/dL <180*

65Q3. What are glycemic treatment goals of DM?

ICU = intensive care unit.

*Provided target can be safely achieved.

Q4. How are glycemic targets achieved

for T2DM?

Therapeutic Lifestyle Changes


Weight loss

(for overweight and

obese patients)

Reduce by 5% to 10%

Physical activity150 min/week of moderate-intensity exercise (eg, brisk walking)

plus flexibility and strength training

Diet

• Eat regular meals and snacks; avoid fasting to lose weight

• Consume plant-based diet (high in fiber, low

calories/glycemic index, and high in

phytochemicals/antioxidants)

• Understand Nutrition Facts Label information

• Incorporate beliefs and culture into discussions

• Use mild cooking techniques instead of high-heat cooking

• Keep physician-patient discussions informal

Healthful Eating Recommendations

Carbohydrate Specify healthful carbohydrates (fresh fruits and vegetables, legumes, whole

grains); target 7-10 servings per day

Preferentially consume lower-glycemic index foods (glycemic index score <55 out of

100: multigrain bread, pumpernickel bread, whole oats, legumes, apple, lentils,

chickpeas, mango, yams, brown rice)

Fat Specify healthful fats (low mercury/contaminant-containing nuts, avocado, certain

plant oils, fish)

Limit saturated fats (butter, fatty red meats, tropical plant oils, fast foods) and trans

fat; choose fat-free or low-fat dairy products

Protein Consume protein in foods with low saturated fats (fish, egg whites, beans); there is

no need to avoid animal protein

Avoid or limit processed meats

Micronutrients Routine supplementation is not necessary; a healthful eating meal plan can

generally provide sufficient micronutrients

Chromium; vanadium; magnesium; vitamins A, C, and E; and CoQ10 are not

recommended for glycemic control

Vitamin supplements should be recommended to patients at risk of insufficiency or

deficiency

Noninsulin Agents Available for T2DClass Primary Mechanism of Action Agent(s) Available as

-Glucosidase

inhibitors

Delay carbohydrate absorption

from intestine

Acarbose

Miglitol

Precose or generic

Glyset

Amylin analogue

Decrease glucagon secretion

Slow gastric emptying

Increase satiety

Pramlintide Symlin

Biguanide

Decrease HGP

Increase glucose uptake in

muscle

MetforminGlucophage or

generic

Bile acid

sequestrant

Decrease HGP?

Increase incretin levels?Colesevelam WelChol

DPP-4 inhibitors

Increase glucose-dependent

insulin secretion


Alogliptin

Linagliptin

Saxagliptin

Sitagliptin

Nesina

Tradjenta

Onglyza

Januvia

Dopamine-2 agonist Activates dopaminergic receptors Bromocriptine Cycloset

Glinides Increase insulin secretionNateglinide

Repaglinide

Starlix or generic

Prandin

DPP-4 = dipeptidyl peptidase; HGP = hepatic glucose production.

Garber AJ, et al. Endocr Pract. 2013;19(suppl 2):1-48. Inzucchi SE, et al. Diabetes Care. 2012;35:1364-1379.

Noninsulin Agents Available for T2DClass Primary Mechanism of Action Agent(s) Available as

GLP-1 receptor

agonists

Increase glucose-dependent

insulin secretion


Slow gastric emptying

Increase satiety

Albiglutide

Dulaglutide

Exenatide

Exenatide XR

Liraglutide

Tanzeum

Trulicity

Byetta

Bydureon

Victoza

SGLT2 inhibitors Increase urinary excretion of

glucose

Canagliflozin

Dapagliflozin

Empagliflozin

Invokana

Farxiga

Jardiance

Sulfonylureas Increase insulin secretion

Glimepiride

Glipizide

Glyburide

Amaryl or generic

Glucotrol or generic

Diaeta, Glynase,

Micronase, or

generic

Thiazolidinediones

Increase glucose uptake in muscle

and fat

Decrease HGP

Pioglitazone

Rosiglitazone

Actos

Avandia

GLP-1 = glucagon-like peptide; HGP = hepatic glucose production; SGLT2 = sodium glucose cotransporter 2.

Garber AJ, et al. Endocr Pract. 2013;19(suppl 2):1-48. Inzucchi SE, et al. Diabetes Care. 2012;35:1364-1379.

Effects of Agents Available for T2D

AGI = -glucosidase inhibitors; BCR-QR = bromocriptine quick release; Coles = colesevelam; DPP4I = dipeptidyl peptidase 4 inhibitors;

FPG = fasting plasma glucose; GLP1RA = glucagon-like peptide 1 receptor agonists; Met = metformin; Mod = moderate; PPG =

postprandial glucose; SGLT2I = sodium-glucose cotransporter 2 inhibitors; SU = sulfonylureas; TZD = thiazolidinediones.

*Mild: albiglutide and exenatide; moderate: dulaglutide, exenatide extended release, and liraglutide.

Met GLP1RA SGLT2I DPP4I TZD AGI Coles BCR-QRSU/

GlinideInsulin Pram

FPG

loweringMod

Mild to

mod*Mod Mild Mod Neutral Mild Neutral

SU: mod

Glinide:

mild

Mod to

marked

(basal

insulin or

premixed)

Mild

PPG

loweringMild

Mod to

markedMild Mod Mild Mod Mild Mild Mod

Mod to

marked

(short/

rapid-

acting

insulin or

premixed)

Mod to

marked



GLP1RA = glucagon-like peptide 1 receptor agonists; Met = metformin; Mod = moderate; NAFLD, nonalcoholic fatty liver disease;

SGLT2I = sodium-glucose cotransporter 2 inhibitors; SU = sulfonylureas; TZD = thiazolidinediones.

*Especially with short/ rapid-acting or premixed.


GlinideInsulin Pram

NAFLD

benefitMild Mild Neutral Neutral Mod Neutral Neutral Neutral Neutral Neutral Neutral

Hypo-

glycemiaNeutral Neutral Neutral Neutral Neutral Neutral Neutral Neutral

SU: mod

to severe

Glinide:

mild to

mod

Mod to

severe*Neutral

WeightSlight

lossLoss Loss Neutral Gain Neutral Neutral Neutral Gain Gain Loss



GlinideInsulin Pram

Renal

impair-ment/

GU

Contra-

indicated

in stage

3B, 4, 5

CKD

Exenatid

e contra-

indicated

CrCl <30

mg/mL

GU

infection

risk

Dose

adjust-

ment

(except

lina-

gliptin)

May

worsen

fluid

retention

Neutral Neutral Neutral

Increased

hypo-

glycemia

risk

Increased

risks of

hypo-

glycemia

and fluid

retention

Neutral

GI adverse

effectsMod Mod* Neutral Neutral* Neutral Mod Mild Mod Neutral Neutral Mod

CHF Neutral Neutral Neutral Neutral† Mod Neutral Neutral Neutral Neutral Neutral Neutral

CVDPossible

benefitNeutral Neutral Neutral Neutral Neutral Neutral Safe ? Neutral Neutral

Bone Neutral Neutral Bone loss NeutralMod

bone lossNeutral Neutral Neutral Neutral Neutral Neutral

AGI = -glucosidase inhibitors; BCR-QR = bromocriptine quick release; Coles = colesevelam; CHF = congestive heart failure; CVD =

cardiovascular disease; DPP4I = dipeptidyl peptidase 4 inhibitors; GI = gastrointestinal; GLP1RA = glucagon-like peptide 1 receptor

agonists; GU = genitourinary; Met = metformin; Mod = moderate; SGLT2I = sodium-glucose cotransporter 2 inhibitors; SU =

sulfonylureas; TZD = thiazolidinediones.

*Caution in labeling about pancreatitis.†Caution: possibly increased CHF hospitalization risk seen in CV safety trial.

Insulin therapy

Monotherapy, Dual Therapy, and

Triple Therapy for T2D


GLP1RA = glucagon-like peptide 1 receptor agonists; Met = metformin; SGLT2I = sodium-glucose cotransporter 2 inhibitors; SU =

sulfonylureas; TZD = thiazolidinediones.

*Intensify therapy whenever A1C exceeds individualized target. Boldface denotes little or no risk of hypoglycemia or weight gain, few

adverse events, and/or the possibility of benefits beyond glucose-lowering.

† Use with caution.

Monotherapy* Dual therapy*

Metformin (or other

first-line agent) plus

Triple therapy*

First- and second-line

agent plus

Metformin GLP1RA GLP1RA

GLP1RA SGLT2I SGLT2I

SGLT2I DPP4I TZD†

DPP4I TZD† Basal insulin†

AGI Basal insulin† DPP4I

TZD† Colesevelam Colesevelam

SU/glinide† BCR-QR BCR-QR

AGI AGI

SU/glinide† SU/glinide†

Pharmacokinetics of Insulin

Agent Onset (h) Peak (h) Duration (h) Considerations

Ba

sa

l

NPH 2-4 4-10 10-16 Greater risk of nocturnal hypoglycemia compared

to insulin analogs

Glargine

Detemir

~1-4 No pronounced

peak*

Up to 24† Less nocturnal hypoglycemia compared to NPH

Ba

sa

l-

Pra

nd

ial Regular U-500 ≤0.5 ~2-3 12-24 Inject 30 min before a meal

Indicated for highly insulin resistant

individuals

Use caution when measuring dosage to

avoid inadvertent overdose

Pra

nd

ial

Regular ~0.5-1 ~2-3 Up to 8 Must be injected 30-45 min before a meal

Injection with or after a meal could increase

risk for hypoglycemia

Aspart

Glulisine

Lispro

Inhaled insulin

<0.5 ~0.5-2.5 ~3-5 Can be administered 0-15 min before a meal

Less risk of postprandial hypoglycemia

compared to regular insulin

* Exhibits a peak at higher dosages.

† Dose-dependent.

NPH, Neutral Protamine Hagedorn.

Moghissi E et al. Endocr Pract. 2013;19:526-535. Humulin R U-500 (concentrated) insulin prescribing information. Indianapolis: Lilly USA, LLC.

Insulin Regimens

• Insulin is required for survival in T1D

• Physiologic regimens using insulin analogs should be

used for most patients

78Q5. How should glycemia in T1D be managed?

Multiple daily injections (MDI)

• 1-2 injections basal insulin per day

• Prandial insulin injections before each meal

Continuous subcutaneous insulin

infusion (CSII)

• Insulin pump using rapid acting insulin analog

Principles of Insulin Therapy in T1D

• Starting dose based on weight

• Range: 0.4-0.5 units/kg per day

• Daily dosing

• Basal

• 40% to 50% TDI

• Given as single injection of basal analog or 2 injections of NPH per day

• Prandial

• 50% to 60% of TDI in divided doses given 15 min before each meal

• Each dose determined by estimating carbohydrate content of meal

• Higher TDI needed for obese patients, those with

sedentary lifestyles, and during puberty

Q5. How should glycemia in T1D be managed?

TDI = total daily insulin.

79

Blood Pressure Targets

81Q7. How should hypertension be managed?


Blood pressureIndividualize on the basis of age, comorbidities, and

duration of disease, with general target of:

Systolic, mm Hg ~130

Diastolic, mm Hg ~80

A more intensive goal (such as <120/80 mm Hg) should be considered for

some patients, provided the target can be safely reached without adverse

effects from medication.

More relaxed goals may be considered for patients with complicated

comorbidities or those experience adverse medication effects.

Blood Pressure Treatment

• Employ therapeutic lifestyle modification• DASH or other low-salt diet

• Physical activity

• Select antihypertensive medications based on BP-lowering effects and ability to slow progression of nephropathy and retinopathy• ACE inhibitors

or

• ARBs

• Add additional agents when needed to achieve blood pressure targets• Calcium channel antagonists

• Diuretics

• Combined /-adrenergic blockers

• -adrenergic blockers

• Do not combine ACE inhibitors with ARBs

82Q7. How should hypertension be managed?

ACE = angiotensin converting enzyme; ARB = angiotensin II receptor blocker; BP = blood pressure; DASH = Dietary Approaches to Stop

Hypertension.

Lipid Targets

83Q8. How should dyslipidemia be managed?

ParameterTreatment Goal

Moderate risk High risk

Primary Goals

LCL-C, mg/dL <100 <70

Non–HDL-C, mg/dL <130 <100

Triglycerides, mg/dL <150 <150

TC/HDL-C ratio <3.5 <3.0

Secondary Goals

ApoB, mg/dL <90 <80

LDL particles <1,200 <1,000

Moderate risk = diabetes or prediabetes with no ASCVD or major CV risk factors

High risk = established ASCVD or ≥1 major CV risk factor

CV risk factors

Hypertension

Family history

Low HDL-C

SmokingApoB = apolipoprotein B; ASCVD = atherosclerotic cardiovascular disease; CV = cardiovascular; HDL-C = high density lipoprotein

cholesterol; LDL = low-density lipoprotein; LDL-C = low-density lipoprotein cholesterol; TC = total cholesterol.

Lipid Management

Elevated LDL-C, non-HDL-C, TG, TC/HDL-C

ratio, ApoB, LDL particles

• Statin = treatment of choice

• Add bile acid sequestrant, niacin, and/or cholesterol absorption inhibitor if target not met on maximum-tolerated dose of statin

• Use bile acid sequestrant, niacin, or cholesterol absorption inhibitor instead of statin if contraindicated or not tolerated

LDL-C at goal but non-HDL-C not at goal(TG ≥200 mg/dL

and/or low HDL-C)

• May use fibrate, niacin, or high-dose omega-3 fatty acid to achieve non-HDL-C goal

TG ≥500 mg/dL

• Use high-dose omega-3 fatty acid, fibrate, or niacin to reduce TG and risk of pancreatitis

84Q8. How should dyslipidemia be managed?

ApoB = apolipoprotein B; HDL-C = high density lipoprotein cholesterol; LDL = low-density lipoprotein; LDL-C = low-density lipoprotein

cholesterol; TC = total cholesterol; TG = triglycerides.

Assessment of Diabetic Nephropathy

85Q9. How is nephropathy managed in patients with

diabetes?

AER = albumin excretion rate; eGFR = estimated glomerular filtration rate; T1D = type 1 diabetes; T2D = type 2 diabetes.

• Annual assessments

• Serum creatinine to determine eGFR

• Urine AER

• Begin annual screening

• 5 years after diagnosis of T1D if diagnosed before age 30 years

• At diagnosis of T2D or T1D in patients diagnosed after age 30

years

Management of Diabetic Nephropathy

• Optimal control of blood pressure, glucose, and lipids

• Smoking cessation

• RAAS blockade

• ACE inhibitor, ARB, or renin inhibitor

• Do not combine RAAS blocking agents

• Monitor serum potassium

• Nephrologist referral

• Atypical presentation

• Rapid decline in eGFR or albuminuria progression

• Stage 4 CKD

87Q9. How is nephropathy managed in patients with

diabetes?

ACE = angiotensin converting enzyme; ARB = angiotensin II receptor blocker; CKD = chronic kidney disease; eGFR = estimated

glomerular filtration rate; RAAS = renin angiotensin aldosterone system.

Assessment of Diabetic Retinopathy

88Q10. How is retinopathy managed in patients with

diabetes?

DM = diabetes mellitus; T1D = type 1 diabetes; T2D = type 2 diabetes.

• Annual dilated eye examination by experienced

ophthalmologist or optometrist

• Begin assessment

• 5 years after diagnosis of T1D

• At diagnosis of T2D

• More frequent examinations for:

• Pregnant women with DM during pregnancy and 1 year postpartum

• Patients with diagnosed retinopathy

• Patients with macular edema receiving active therapy

Management of Diabetic Retinopathy

89Q10. How is retinopathy managed in patients with

diabetes?


• Slow retinopathy progression by maintaining optimal

control of

• Blood glucose

• Blood pressure

• Lipids

• For active retinopathy, refer to ophthalmologist as needed

• For laser therapy

• For vascular endothelial growth factor therapy

Assessment of Diabetic Neuropathy• Complete neurologic examination annually

• Begin assessment

• 5 years after diagnosis of T1D

• At diagnosis of T2D

90Q11. How is neuropathy diagnosed and managed in


T1D = type 1 diabetes; T2D = type 2 diabetes.

Diabetic Neuropathy Evaluations and Tests

Foot inspection Foot structure and deformities

Skin temperature and integrity

Ulcers

Vascular status

Pedal pulses

Amputations

Neurologic testing Loss of sensation, using 1 and 10-g monofilament

Vibration perception using 128-Hz tuning fork

Ankle reflexes

Touch, pinprick, and warm and cold sensation

Painful neuropathy May have no physical signs

Diagnosis may require skin biopsy or other surrogate measure

Cardiovascular

autonomic neuropathy

Heart rate variability with:

• Deep inspiration

• Valsalva maneuver

• Change in position from prone to standing




Diabetic Neuropathy Management

All neuropathies • Prevent by controlling blood glucose to individual targets

• No therapies proven to reverse neuropathy once it is

established

• May slow progression by maintaining optimal glucose, blood

pressure, and lipid control and using other interventions that

reduce oxidative stress

Painful neuropathy • Tricyclic antidepressants, anticonvulsants, serotonin reuptake

inhibitors, or norepinephrine reuptake inhibitors

Large-fiber

neuropathies

• Strength, gait, and balance training

• Orthotics to prevent/treat foot deformities

• Tendon lengthening for pes equinus

• Surgical reconstruction

• Casting

Small-fiber

neuropathies

• Foot protection (eg, padded socks)

• Supportive shoes with orthotics if needed

• Regular foot inspection

• Prevention of heat injury

• Emollient creams



Comprehensive Management of CV Risk

• Manage CV risk factors

• Weight loss

• Smoking cessation

• Optimal glucose, blood pressure, and lipid control

• Use low-dose aspirin for secondary prevention of CV

events in patients with existing CVD

• May consider low-dose aspirin for primary prevention of CV events

in patients with 10-year CV risk >10%

• Measure coronary artery calcification or use coronary

imaging to determine whether glucose, lipid, or blood

pressure control efforts should be intensified

93Q12. How is CVD managed in patients with diabetes?

CV = cardiovascular; CVD = cardiovascular disease.

Self-monitoring of Blood Glucose (SMBG)

95

SMBG, self-monitoring of blood glucose.

Q18. When and how should glucose monitoring be used?

Noninsulin Users Insulin Users

Introduce at diagnosis

Personalize frequency of

testing

Use SMBG results to inform

decisions about whether to

target FPG or PPG for any

individual patient

All patients using insulin should

test glucose

≥2 times daily

Before any injection of insulin

More frequent SMBG (after

meals or in the middle of the

night) may be required

Frequent hypoglycemia

Not at A1C targetTesting positively affects glycemia in

T2D when the results are used to:

• Modify behavior

• Modify pharmacologic treatment

Vaccinations for Patients with DM

Vaccine, frequency of administration Patient age

Routine childhood immunizations, according to standard schedule

(eg, measles, mumps, rubella, varicella, polio, tetanus-diphtheria)6 months to 18 years

Influenza, annually ≥6 months

Pneumococcal polysaccharide vaccine ≥2 years

PVC13, 1-2 injections 2-18 years

PPSV23, 1 injection 19-64 years

PVC13 plus PPSV23,

1 injection each, in series≥65 years

Hepatitis B, 1 injection 20-59 years*

Tetanus-diphtheria booster, every 10 years in adults ≥19 years

Individuals not already immunized for childhood diseases and those

requiring vaccines for endemic diseases should be immunized as

required by individual patient needs

Any age

*Consider for patients ≥60 based on assessment of risk and likelihood of adequate immune response.

96Q21. What vaccinations should be given to patients with

diabetes?

DM and Depression

97Q22. How should depression be managed in the context of

diabetes?

• Screen all adults with DM for depression

• Untreated comorbid depression can have serious clinical

implications for patients with DM

• Consider referring patients with depression to mental

health professionals who are knowledgeable about DM

DM and Cancer

• Screen obese individuals with DM more frequently and

rigorously for certain cancers

• Endometrial, breast, hepatic, bladder, pancreatic, colorectal cancers

• Increased BMI (≥25 kg/m2) also increases risk of some

cancers

• Strong associations: endometrial, gall bladder, esophageal , renal,

thyroid, ovarian, breast, and colorectal cancer

• Weaker associations: leukemia, malignant and multiple melanoma,

pancreatic cancer, non-Hodgkin lymphoma

• To date, no definitive relationship has been established

between specific hyperglycemic agents and increased risk of

cancer or cancer-related mortality

• Consider avoiding medications considered disadvantageous to

specific cancers in individuals at risk for or with a history of that cancer

98Q23. What is the association between diabetes and

cancer?

DM and Occupational Hazards

99Q24. Which occupations have specific diabetes

management requirements?

• Commercial drivers at high risk for developing T2D

• Screen as appropriate

• Encourage healthy lifestyle change

• Be aware of management requirements and use agents

with reduced risk of hypoglycemia in patients with

occupations that could put others at risk, such as (not

inclusive):

• Commercial drivers

• Pilots

• Anesthesiologists

• Commercial or recreational divers

INCREASED STROKE RISK IN SOME

PATIENTS WITH SUBCLINICAL

HYPOTHYROIDISM

Reuters Health Information

Subclinical hypothyroidism(SCH)

• Associated with cardiovascular disease risk factors

• Many of which are shared with stroke

• Recent systematic review and meta-analysis found no

association between subclinical hypothyroidism and the

risk of stroke

• Dr. Robin P. Peeters from Erasmus Medical Center in

Rotterdam, the Netherlands, and colleagues

• Conducted an analysis of individual data from more than

47,500 participants in 17 prospective cohort studies that

assessed stroke events and/or fatal stroke

SCH and stroke

• SCH: hypercholesterolemia, atherosclerosis, and an

increased carotid intima-media thickness

• Risk of CVD in younger populations

• CVD: Stroke?

• Determine the risk of stroke associated with subclinical

hypothyroidism.

Data Sources and Study Selection

• Published prospective cohort studies

• Unpublished studies from Thyroid Studies Collaboration

• Thyroid function and stroke outcome

• Subclinical hypothyroidism

• TSH levels 4.5–19.9 mIU/L

• Normal thyroxin levels.

Results

• 18 prospective cohort studies

• USA, Europe, Australia, Brazil and Japan

• 47,573 participants

• From 1972 to 2014

• Median follow-up ranging between 1.5 and 20 years and a

• Total follow-up of 489,192 person-years

• SCH prevalence 0.4-16.3%

• Overall average of 7.3%

• 62% female

Risk of Stroke Events in Subclinical

Hypothyroidism vs Euthyroidism

2547 stroke events occurred

Risk of Fatal Stroke in Subclinical

Hypothyroidism vs Euthyroidism

1014 fatal stroke

Stratified Analyses for Stroke events

Stratified Analyses for Fatal Stroke events

HRs stratified by age

HRs stratified by TSH level

Summary

• No association between subclinical hypothyroidism and

overall risk of stroke events or fatal stroke

• Younger participants(particularly<50 years), had

increased stroke risk, though the number of events was

small.

• Treatment of subclinical hypothyroidism will result in a

decrease of risk of stroke in younger subjects??

• Need further study

FDA PANEL BACKS NEW SAFETY

WARNINGS ON TWO DIABETES

DRUGS

Medscape Medical News

Label updated

• FDA advisory committee

• Saxagliptin (Onglyza, Bristol-Myers Squibb/AstraZeneca)

• Alogliptin (Nesina, Takeda)

• Information about new safety issues

• From their cardiovascular-outcomes studies

Saxagliptin

• 14 of 15 panelists from the Endocrinologic and Metabolic

Drugs Advisory Committee

• Voted for primarily on the increased risk for heart failure

• They also wanted to see information on the trend toward

higher all-cause mortality.

• One panel member voted to withdraw the drug from the

US market

• Data from SAVOR-TIMI 53

SAVOR-TIMI 53

• The primary end point (Panel A)

• composite of death from cardiovascular causes, myocardial infarction, or ischemic stroke.

• The secondary end point (Panel B)

• composite of death from cardiovascular causes, myocardial infarction, ischemic stroke, hospitalization for unstable angina, coronary revascularization, or heart failure.

SciricaBM et al. N EnglJ Med 2013;369:1317-1326.

Prespecified Clinical End Points.

Prespecified Clinical End Points

SciricaBM et al. N EnglJ Med 2013;369:1317-1326.

Alogliptin

• 13 in 16 voted to add new label data

• New safety information focus on heart failure,

• Despite a lack of a real signal

• Some felt that heart failure could be a classwide

problem

Alogliptin Heart-Failure Data Confusing

• FDA conducted additional exploratory analyses of heart

failure in EXAMINE

• 89 placebo patients had at least one heart-failure

hospitalization event compared with 106 alogliptin

patients,

• Hazard ratio of 1.19 (95% confidence interval, 0.90 –

1.58).

• EXAMINE was not primarily designed to formally evaluate

heart failure.

Other Studies Expected Soon

• The next to be released — in June

• Randomized Placebo Controlled Clinical Trial to Evaluate

Cardiovascular Outcomes after Treatment with Sitagliptin

in Patients with Type 2 Diabetes Mellitus and Inadequate

Glycemic Control on Mono- or Dual Combination Oral

Antihyperglycemic Therapy (TECOS)

• Conducted by Merck.

STATINS FOR PRIMARY

PREVENTION IN EVERYONE 75

YEARS AND OLDER? IT COULD BE

COST-EFFECTIVE: ANALYSIS

Ann Intern Med. 2015;162:533-541.

doi:10.7326/M14-1430

Trial

• Commonly prescribed statin for primary prevention in

elderly patient (>75 yr)

• Unclear effectiveness role for primary prevention

• Objective:

• project the population impact and cost- effectiveness of statin

therapy in adults aged 75 years or older.

• Targeted population: US population, 75-94 years old

• Intervention:

• Statins for primary prevention

• Based on LDL level: 130,160 and 190 mg/dL

• presence of diabetes

• 10-year risk score of at least 7.5%

Outcomes

• Myocardial infarction (MI)

• Coronary heart disease (CHD) death

• Disability-adjusted life-years

• Costs

• Simulation model

Results of Base-Case Analysis

• All adults aged > 75 years

• 10-year risk score > 7.5%

• If statins had no effect on functional limitation or cognitive

impairment

• All primary prevention strategies would prevent MIs and

CHD deaths and be cost-effective.

• Treatment of all adults aged 75 to 94 years

• 8 million additional users

• prevent 105000 (4.3%) incident MIs and 68000 (2.3%) CHD deaths

• Incremental cost per disability-adjusted life-year of $25 200

Results of Sensitivity Analysis

• Increased relative risk for functional limitation or mild

cognitive impairment

• 1.10 to 1.29

• Offset the cardiovascular benefits

Statin

• Cost-effective for primary prevention

• Older adults]

• however, even a small increase in geriatric-specific

adverse effects could

• 10% to 30% increased risk for these adverse effects

Key Take-Homes

• Despite low cost and high potential benefit

• Very modest adverse effects

• Attributable to statins tip the balance in the direction of

harm

• Cognitive impairment: required further investigation

Conclusion

• Statins are projected to be cost-effective for primary

prevention

• Small increase in geriatric-specific adverse effects could

offset the cardiovascular benefit.

• Improved data on the potential benefits and harms of

statins are needed to inform decision making.

Med scape April2015

Health & Medicine

Transcript of Med scape April2015