Transcript Diabetes Therapy in the Elderly

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
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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
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Hypoglycemic Risk
Hepatic Substrates*
Hypoglyce
mia
Requires
Insulin for
Efficacy
Metformin
Yes (with
insulin)
Yes
Glyburide
Yes
No
Glipizide
Yes
Glimepiride
Drug
Substrate
Major CYP
Enzyme
Glipizide
2C8/9
Glimepiride
2C9
No
Repaglinide
2C8/9, 3A4
Yes
No
Nateglinide
2C8/9, 3A4
Repaglinide
No
No
Rosiglitazone
2C8
Nateglinide
No
No
Pioglitazone
2C8
Acarbose
No
Yes
Miglitol
No
Yes
Rosiglitazon
e
Yes (with
insulin)
Yes
Pioglitazone
Yes (with
insulin)
Yes
Exenatide
No
No
Sitagliptin
No
No
*Only major enzymes listed. Induction and inhibition omitted.
Data per Lexi-comp Drug Information Handbook 14th Ed.
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Drug Use Precautions*
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
Renal Impairment
Avoidance
Contraindications
Metformin
SCr >1.5 mg/dl Males
SCr >1.4 mg/dl Females
eGFR <30
avoid Clcr< 60-70 ml/min
Caution 80+ yo
Dialyzable 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
Allergy
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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)
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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
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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.
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Tighter Control
• Tighter control can be achieved with mealtime rapidacting 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.
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Insulin Actions
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American Geriatrics Society Guidelines and Other Principles
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References
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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.
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