1. Nephrology Core Curriculum Diabetes Management in ESRD

2. Oral Agents Sulfonylureas and Meglitinides 1st Generation- –acetohexamide, chlorpropamide, tolbutamide 2nd Generation –Glipizide (Glucitrol), Glyburide (Glynase, Diabeta, Micronase), Glimepride

3. 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)

4. Oral Agents Sulfonylureas and Meglitinides Glipizide – hepatically cleared. Multiple metabolites (inactive) and cleared by the kidney –NO RENAL DOSING REQUIRED-- EVEN WITH XL FORMULATION AND SEVERE ESRD

5. Oral Agents Sulfonylureas 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)

6. Oral Agents Sulfonylureas 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

7. Oral Agents Sulfonylureas 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

8. Oral Agents Glitazones 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

9. Oral Agents Glitazones 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

10. Oral Agents Insulin 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

11. Oral Agents Glitazones Up to 6 weeks before full effect- titrate qmonth max