Transcript DM2_Care_with_ESRD

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