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 Courtesy of DiabetesinControl.com

Hepatic Substrates* Substrate Major CYP Enzyme Glipizide2C8/9 Glimepiride2C9 Repaglinide2C8/9, 3A4 Nateglinide2C8/9, 3A4 Rosiglitazone2C8 Pioglitazone2C8 *Only major enzymes listed. Induction and inhibition omitted. Data per Lexi-comp Drug Information Handbook 14th Ed. Hypoglycemic Risk Drug Hypoglyce mia Requires Insulin for Efficacy Metformin Yes (with insulin) Yes GlyburideYesNo GlipizideYesNo GlimepirideYesNo RepaglinideNo NateglinideNo AcarboseNoYes MiglitolNoYes Rosiglitazon e Yes (with insulin) Yes Pioglitazone Yes (with insulin) Yes ExenatideNo SitagliptinNo Courtesy 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* DrugRenal Impairment Avoidance Contraindications MetforminSCr >1.5 mg/dl Males SCr >1.4 mg/dl Females eGFR <30 avoid Clcr< ml/min Caution 80+ yo Dialyzable 170 ml/min CHF requiring meds GlyburideClcr <50 ml/minDKA GlipizideClcr <10 ml/minSevere hepatic disease GlimepirideClcr <22 ml/min (initiate at 1 mg) DKA RepaglinideClcr ml/min (initiate 0.5 mg with meals) NateglinideNo adjustmentDKA MiglitolScr >2 mg/dLIntestinal disorders, DKA AcarboseClcr <25 ml/min (6 times AUC increase) Intestinal disorders, DKA RosiglitazoneNo adjustment. Watch hepatic failure. Transaminases >2.5 times the upper limit of normal. Class 3/4 CHF PioglitazoneNo adjustment. Watch hepatic failure. Transaminases >2.5 times the upper limit of normal. Class 3/4 CHF ExenatideClcr <30 ml/minDKA SitagliptinAdjust DoseAllergy Courtesy 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) Courtesy of DiabetesinControl.com

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 Courtesy of DiabetesinControl.com

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. Courtesy of DiabetesinControl.com

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 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. Courtesy of DiabetesinControl.com

Insulin Actions Courtesy of DiabetesinControl.com

American Geriatrics Society Guidelines and Other Principles Courtesy of DiabetesinControl.com

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, 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, Courtesy of DiabetesinControl.com