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Oral Agents Sulfonylureas and Meglitinides Chlorpropamide –most severe post-ETOH flushing reaction –hyponatremia 2nd increased vasopressin release can use to treat a partial DI Glyburide –NOT RECCOMENDED IF GFR < 50cc/min –increased effect with quinolones, H2-blockers, anticoagulants, TCA or any other drug with significant protein binding (displaces glyburide)
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Nephrology Core CurriculumDiabetes Management in ESRD
Oral AgentsSulfonylureas and Meglitinides
• 1st Generation-– acetohexamide, chlorpropamide, tolbutamide
• 2nd Generation– Glipizide (Glucitrol), Glyburide (Glynase,
Diabeta, Micronase), Glimepride
Oral AgentsSulfonylureas and Meglitinides
• Chlorpropamide– most severe post-ETOH flushing reaction– hyponatremia 2nd increased vasopressin release
• can use to treat a partial DI
• Glyburide– NOT RECCOMENDED IF GFR < 50cc/min– increased effect with quinolones, H2-blockers,
anticoagulants, TCA or any other drug with significant protein binding (displaces glyburide)
Oral AgentsSulfonylureas and Meglitinides
• Glipizide– hepatically cleared. Multiple metabolites
(inactive) and cleared by the kidney– NO RENAL DOSING REQUIRED-- EVEN
WITH XL FORMULATION AND SEVERE ESRD
Oral AgentsSulfonylureas and Meglitinides
• Glimepride– has the lowest dose (use in elderly or recurrent
hypoglycemia despite lowest dose of Glucitrol)– can use with decreased GFR with caution
• 60% excreted in urine by 7 days-- but all in the form of a partially active metabolite (30% of parent activity)
– PDR- if GFR <22cc/min-- requires only 1mg/day (14 cents vs. 17 cents for gluc xl)
Oral AgentsSulfonylureas and Meglitinides
• Meglitinides– Repaglinide (Prandin)– Starlix
• structurally distinct from sulfonylureas-- but acts at the pancreas in a similar fashion
• more expensive without clear-cut advantage (like ACE-I and ARBs)– use only if contraindication to sulfonylurea-- drug
reaction or recurrent hypoglycemia
Oral AgentsSulfonylureas and Meglitinides
• Meglitinides– very short onset of action and duration of
action-- can dose according to po intake• miss a meal-- skip a dose---- no risk of
hypoglycemia as with sulfonylureas– RENAL-- 98% protein bound-- no renal issues– take pre-prandial up to 4mg TID
Oral AgentsGlitazones
• Rosi– 2mg/day to a max of 8mg (usually bid)– can’t take with insulin
• Pio (Actos)– 15mg-45mg/day. May cause Fe-defn anemia– true qd drug
• Side Effects– both-- mild to moderate edema (5-7% of patients)-- use with caution in
severe CHF and liver failure– inc sub-q fat deposition and weight gain
• No renal issues• Don’t give to skinny or non-insulin resistant
Oral AgentsGlitazones
• Actos– decreases trigly, inc HDL, and neutral effect on LDL (changes
range from 10-20% of baseline)– weight gain-- avg .1-2kg– adding to sulfonylurea-- decrease a1c by .9-1.3%– mean Hgb values can decrease 2-4%– check lfts pre-treatment– max dose 45-- although dose titration not recc for renal
insufficiency– can take without regard to food
Oral AgentsInsulin
• Insulin requirements usually only decrease 25% when going from a normal GFR to 10cc/min. It is only less than 10cc/min when you see a profound decrease in insulin requirements
• Newer formulations– Lispro-onset 15minutes, peak 1-1.5hr, and duration 4-6hr– Glargine (Lantus)
• rDNA produced-- human insulin with a substituted glycine and two arginines at b-terminus. Soluble at pH 4.0-- but insoluble at a neutral pH. So once injected-- leads to microcrystals which gradually dissolve over 24hr without a peak.
• No studies in renal patients-- use with caution (per PDR)• Administer at bedtime• Switching from NPH-- start lantus at 80% of total NPH dose
Oral AgentsGlitazones
• Up to 6 weeks before full effect- titrate qmonth max
