Safety and efficacy of once-weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes over 84 weeks

Abstract

Objective: We recently reported that after 26 weeks, exenatide once weekly (EQW) resulted in superior A1C reduction, reduced hypoglycemia, and progressive weight loss compared with daily insulin glargine (IG) in patients with type 2 diabetes who were taking metformin alone or with sulfonylurea. This 84-week extension study assessed the long-term safety and efficacy of EQW versus IG.

Research design and methods: This multicenter, open-label, randomized, two-arm, parallel trial assessed change in A1C, proportions of patients achieving A1C <7.0 and ≤6.5%, body weight, incidence of hypoglycemia, and overall safety.

Results: Of 415 patients who completed 26 weeks, 390 (194 EQW and 196 IG patients) entered the extension study. At 84 weeks, A1C decreased from baseline (8.3%) by -1.2% for EQW vs. -1.0% for IG (P = 0.029). The proportions of patients who achieved end point A1C targets <7.0 and ≤6.5% were 44.6% for EQW patients vs. 36.8% for IG patients (P = 0.084) and 31.3% for EQW patients vs. 20.2% for IG patients (P = 0.009), respectively. Patients taking EQW lost 2.1 kg of body weight, whereas those taking IG gained 2.4 kg (P < 0.001). Among patients taking metformin plus sulfonylurea, the incidence of minor hypoglycemia was 24% for EQW patients vs. 54% for IG patients (P < 0.001); among patients taking metformin alone, it was 8% for EQW patients vs. 32% for IG patients (P < 0.001). Among adverse events occurring in ≥5% of patients, diarrhea and nausea occurred more frequently (P < 0.05) in the EQW group than in the IG group (12 vs. 6% and 15 vs. 1%, respectively).

Conclusions: After 84 weeks, patients treated with EQW continued to experience better glycemic control with sustained overall weight loss and a lower risk of hypoglycemia than patients treated with IG.

Figure 1

Patient flow through study. A number of patients were screened, randomly assigned, and participated in the study. Reasons for discontinuation are provided in the following footnotes. ^aDiscontinued as a result of subject decision. Although these patients were not included in the ITT analysis set, they are counted in the number of patients who discontinued before week 84. ^bNumber of patients who required a change in their study treatment at or after week 48. These patients were included in the ITT analysis set, using their last observation before treatment change carried forward. ^cReasons for discontinuation: AEs (n = 16), subject decision (n = 14), protocol violation (n = 12), completed 26-week core treatment period and chose not to continue in open-ended extension period (n = 9), entry criteria not met (n = 3), physician decision (n = 3), lost to follow-up (n = 2), and sponsor decision (n = 1). ^dReasons for discontinuation: subject decision (n = 30), completed 26-week core treatment period and chose not to continue in open-ended extension period (n = 14), protocol violation (n = 7), AEs (n = 4), physician decision (n = 2), lost to follow-up (2), and entry criteria not met (n = 2).

Figure 2

Effects of EQW vs. IG on A1C and body weight over 84 weeks of therapy. A: A1C values over time for the ITT population. B: A1C values over time for the 84-week completer population. C: Body weight change over time for the ITT population. D: Body weight change over time for the 84-week completer population. ●, EQW; ○, IG. *P < 0.05.