Gerti Tashko, M.D. DM Journal Club 12/16/2010

The use of exenatide with insulin is not FDA approved. The study was designed to evaluate if exenatide (byetta) addition to basal insulin (glargine) improves A1c.

Inclusion Criteria: DM2 with A1c of 7.1% % Age > 18 Glargine use of ≥ 20 units/day, with  Metformin,  Pioglitazone,  both BMI < 45 kg/m 2 Stable body weight (not > 5% wt ∆ in 3 months)

Design: This was a parallel, randomized, placebo- controlled trial, where patients with the above criteria were split to receive for 30 weeks either exenatide 10 mcg BID or placebo injections BID, in addition to basal glargine  PO meds (met, pio, both). The study took place in 59 centers & 5 countries.

Primary Outcome: Primary outcome was the ∆ in A1c between treatment group and control at 30 weeks.

Secondary Outcomes: # of pts with A1c < 7.0 % # of pts with A1c < 6.5 % 7-point self monitored glucose profile (7-SMBG) Body weight Waist circumference Insulin dose Hypoglycemia events Adverse events.

At randomization … … subjects with A1c > 8.0% continued with their current dose of glargine, but those with A1c < 8.0% had the glargine reduced by 20%. The insulin doses were kept stable for 5 weeks (until exenatide began to work fully) After 5 weeks, investigators titrated dose of insulin at least weekly from weeks 5-10, and every 2 weeks from weeks 10-30, with the final goal of fasting glucose < 100 mg/dL

Selected:

Results: Primary Outcome

Results: Secondary Outcomes

Conclusion: Addition of Exenetide to Glargine lowers A1c by 0.7% at 30 weeks. – The A1c lowering effect appears to be primarily due to the significant decreases in glucose values 2 hours after administration of Exenetide. – Exenetide also helps lowering the body weight by 2.74 kg. – sBP and dBP also improve significantly (although slightly due to normal baseline values). Weight loss could be the contributing factor. Side effects like GI symptoms and HA are more prominent in patients receiving Exenetide, however they seem to disappear after 10 weeks of use. – Addition of Exenetide did not change the rate of hypoglycemic events.