Exenatide efficacy and safety: a systematic review

OBJECTIVE: To examine the efficacy, effectiveness and side effects of exenatide when compared with oral glucose-lowering agents or insulin therapy. RESEARCH DESIGN AND METHODS: Relevant citations were identified from searches of multiple bibliographic databases supplemented with searches of the US Food and Drug Administration website and other sources. A qualitative synthesis was performed, with a random effects meta-analysis when appropriate. RESULTS: We identified 17 studies. In placebo-controlled trials of subjects with poorly controlled diabetes (with both groups receiving various oral glucose-lowering agents), exenatide 10 microg twice daily improved glycated haemoglobin (HbA(1c)) by approximately 1.0% over 30 weeks pooled estimate -0.97%, 95% confidence interval (CI), -1.16 to -0.79%, P < 0.0001 and exenatide treatment over 16-30 weeks was associated with weight loss of 1.0-2.5 kg. Exenatide appeared to confer a similar benefit to various insulin regimes for glycaemic control at follow-up between 16 and 52 weeks (pooled estimate HbA(1c)-0.04%, 95% CI, -0.14 to 0.06%, P = 0.41), but was advantageous over insulin with respect to weight loss (3-6 kg loss at up to 52 weeks of follow-up). Nausea was the most common adverse event in placebo- and active-controlled trials. Rates of hypoglycaemia were similar in exenatide and insulin groups, but were higher with exenatide 10 microg twice daily compared with placebo and hypoglycaemia was most frequent when a sulphonylurea was administered. CONCLUSIONS: In subjects with poorly controlled diabetes, exenatide was associated with a reduction in HbA(1c) that was similar to introducing another oral agent or insulin. Weight loss may be an advantage with exenatide. Long-term studies in diverse and unselected populations are needed to clarify the benefit vs. harm profile of this drug.