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 mu g 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 mu g 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.