Clinical Implications of Exenatide as a Twice-Daily or Once-Weekly Therapy for Type 2 Diabetes

Exenatide (exendin-4) is a 39-amino acid peptide belonging to the glucagon-like peptide-1 (GLP-1) receptor agonist class that has been demonstrated to improve glycemic control in patients with type 2 diabetes mellitus. Exenatide can be injected twice daily (ExBID) before meals or once weekly (ExQW) when encompassed within dissolvable poly-(D,L-lactide-co-glycolide) microspheres. The primary difference between these formulations is the plasma concentration of exenatide over time, with the long-acting form providing continuous delivery. Clinical trials have examined the similarities and differences in the efficacy and safety/tolerability outcomes of these formulations. In 2 clinical studies spanning 24 and 30 weeks, significant (P < 0.05) reductions from baseline were observed in fasting plasma glucose (ExBID, -12 and -25 mg/dL; ExQW, -35 and -41 mg/dL), postprandial glucose (ExBID, -124 mg/dL; ExQW, -95 mg/dL), and glycated hemoglobin (HbA1c) (ExBID, -0.9% and -1.5%; ExQW, -1.6% and -1.9%). Reductions in body weight from baseline were significant and similar with both treatments (ExBID, -1.4 and -3.6 kg; ExQW, -2.3 and -3.7 kg). Reductions in systolic blood pressure from baseline were observed with both formulations, particularly in patients who were hypertensive at baseline. Beneficial improvements in lipid profiles were small and fluctuated in significance. Patients reported greater treatment satisfaction with ExQW compared with ExBID dosing. Gastrointestinal adverse events were commonly observed with both formulations but were less frequent with ExQW. These events were of mild-to-moderate intensity and rarely led to discontinuation. Real-world data for ExBID demonstrated decreases in HbA1c, fasting plasma glucose, and body weight that were consistent with clinical trial results. Cases of pancreatitis or renal impairment have been reported in patients treated with ExBID, although no causal relationship with treatment has been shown. This review describes the similarities and differences between exenatide delivered as a twice-daily or as a once-weekly injection to provide a better understanding of the clinical effects and potential clinical uses of each.