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Nephrology Core Curriculum Diabetes Management in ESRD Oral Agents Sulfonylureas and Meglitinides • 1st Generation– acetohexamide, chlorpropamide, tolbutamide • 2nd Generation – Glipizide (Glucitrol), Glyburide (Glynase, Diabeta, Micronase), Glimepride 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) 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 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) 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 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 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 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 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 Oral Agents Glitazones • Up to 6 weeks before full effect- titrate qmonth max