diabetes therapy in the elderly epidemiology –>20% of patients over 65 have dm2 –10% of...

Diabetes Therapy in the Elderly

• Epidemiology– >20% of patients over 65 have DM2– 10% of diabetes cases are diagnosed after the age of 65

• Research and Evidence– No long term studies in the geriatric population– Heterogeneity necessitates a patient centered approach

• Treatment Guidelines– Uncomplicated healthy geriatric patients may adhere to the

same goals and therapy recommendations as younger patients– “Start Low, and Go Slow”– Frail patients at risk for hypoglycemia, those with functional or

cognitive impairment, and those with a life expectancy of < 5 years may have less intensive goals

• FBG <150 mg/dl and HbA1c 7-8 are acceptable endpoints

Courtesy of DiabetesinControl.com

The Main Concerns• Hypoglycemia

– Neuroglycopenic manifestations • Dizziness, weakness, delirium, confusion• More common• May be confused with a TIA

– Adrenergic manifestations • Tremors and sweating• Less common

– Increased risk for falls and fracture may lead to injury and nursing home placement

• Polypharmacy– CYP 2C8/9, 3A4 substrates– Drug Interactions

• Sulfonamides (Septra) increase incidence of hypoglycemia• Ketoconazole inhibits pioglitazone metabolism• Gemfibrozil increases insulin sensitivity, decreases glucagon secretion and inhibits

CYP 2C8• Beta-blockers may mask hypoglycemic symptoms


Hepatic Substrates*

SubstrateMajor CYP

Enzyme

Glipizide 2C8/9

Glimepiride 2C9

Repaglinide 2C8/9, 3A4

Nateglinide 2C8/9, 3A4

Rosiglitazone 2C8

Pioglitazone 2C8

*Only major enzymes listed. Induction and inhibition omitted.Data per Lexi-comp Drug Information Handbook 14th Ed.

Hypoglycemic Risk

DrugHypoglyce

mia

Requires Insulin for Efficacy

MetforminYes (with insulin)

Yes

Glyburide Yes No

Glipizide Yes No

Glimepiride Yes No

Repaglinide No No

Nateglinide No No

Acarbose No Yes

Miglitol No Yes

Rosiglitazone

Yes (with insulin)

Yes

PioglitazoneYes (with insulin)

Yes

Exenatide No No

Sitagliptin No NoCourtesy of

DiabetesinControl.com

Other Concerns

• Age related decline in renal function requires changes in drug therapy

• Comorbid conditions such as congestive heart failure can lead to altered kidney function and increased risk for lactic acidosis

• Hepatic disease can lead to decreased drug metabolism

Drug Use Precautions*

Drug Renal Impairment Avoidance

Contraindications

Metformin SCr >1.5 mg/dl MalesSCr >1.4 mg/dl FemaleseGFR <30avoid Clcr< 60-70 ml/minCaution 80+ yoDialyzable 170 ml/min

CHF requiring meds

Glyburide Clcr <50 ml/min DKA

Glipizide Clcr <10 ml/min Severe hepatic disease

Glimepiride Clcr <22 ml/min (initiate at 1 mg)

DKA

Repaglinide Clcr 20-40 ml/min(initiate 0.5 mg with meals)

Nateglinide No adjustment DKA

Miglitol Scr >2 mg/dL Intestinal disorders, DKA

Acarbose Clcr <25 ml/min(6 times AUC increase)

Intestinal disorders, DKA

Rosiglitazone No adjustment.Watch hepatic failure.

Transaminases >2.5 times the upper limit of normal. Class 3/4 CHF

Pioglitazone No adjustment.Watch hepatic failure.

Transaminases >2.5 times the upper limit of normal. Class 3/4 CHF

Exenatide Clcr <30 ml/min DKA

Sitagliptin Adjust Dose AllergyCourtesy of

DiabetesinControl.com

Preferred Non-Insulin Agents

• Good Qualities– Low Risk of Hypoglycemia– Few Drug Interactions– Low Side Effect Profile– Low Pill Burden

• For obese patients– Metformin, Exenatide

• For patients with severe renal failure– Sitagliptin Saxagliptin– Glipizide (caution with hypoglycemia)


Specific Precautions

• Metformin use in heart failure or renal failure• Miglitol and Acarbose in patients prone to dehydration• TZDs in heart failure or hepatic failure. May cause or

exacerbate edema.• Chlorpropamide due to increased risk for hypoglycemia

and long duration of action.• Glyburide due to rapid and prolonged hypoglycemia

despite hypertonic glucose injections.• Exenatide in malnourished patients or those on

concomitant medications which cause nausea or vomiting


Insulin Therapy• Evaluate the physical and intellectual capacity of the patient to

identify, measure and deliver appropriate doses of insulin and other injected medications, to monitor blood glucose, and to recognize and treat hypoglycemia. – Dementia, Alzheimer’s, Parkinson’s, Tremors

• Lower doses may be recommended in patients with a GFR < 50 ml/min due to increased insulin sensitivity.

• Treatment should be uncomplicated and the use of prefilled pens should be encouraged. – Insulin glargine once daily in the morning in combination with oral

therapy is simple and provides good benefits. – For obese patients, exenatide may provide the added benefit of weight

loss with similar HbA1c benefits as glargine.– Pre-mixed insulin analogs provide the advantage of less hypoglycemia

and better postprandial control with similar HbA1c results but are primarily useful in patients with regular meals and unvarying calorie intake.


Tighter Control

• Tighter control can be achieved with mealtime rapid-acting insulin analogs given based on carbohydrate counting, a sliding scale, or body weight calculation

• For patients who can count carbohydrates– initiate 1 unit of insulin for every 10-15 grams of carbohydrates.

• For those unable to count carbs– use a sliding scale where 2 units of quick-acting insulin is used

for every 50 mg/dl above 150 mg/dl 1 hour after a meal.

• Weight based approach– 0.1 unit/kg may be used– discouraged because this may overestimate insulin need.


Insulin Actions


American Geriatrics Society Guidelines and Other Principles


References• Brown AF, Mangione CM, Saliba D, Sarkisian CA: Guidelines for improving the care of the older

person with diabetes mellitus. J Am Geriatr Soc 51:S265-S280, 2003.• American Diabetes Association: Standards of Medical Care inDiabetes 2007 Diabetes Care 30:

S4-41S.• Lexi-comp. Drug Information Handbook. 14 th Edition.• Pri-med Clinical Focus in Diabetes Presentation. Identifying and Stratifying Diabetes and CVD

Risk in Your Patient Population. Presented 04/14/2007.

• McCulloch DK, Munshi M. Treatment of diabetes mellitus in the elderly. In: UpToDate, Rose, BD

(Ed), UpToDate, Waltham, MA, 2007.


diabetes therapy in the elderly epidemiology –>20% of patients over 65 have dm2 –10% of...

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