To compare the efficacy and safety of adding the glucagon-like peptide-1 receptor agonist exenatide once weekly (QW) 2 mg or placebo among patients with type 2 diabetes inadequately controlled despite titrated insulin glargine (IG) ± metformin.
This multicentre, double-blind study randomized (1:1) patients with persistent hyperglycaemia after 8-week IG titration (glycated haemoglobin [HbA1c] 7.0–10.5% [53–91 mmol/mol]) to exenatide QW or placebo. The primary endpoint was HbA1c change from baseline to week 28. Secondary endpoints included body weight, 2-hour postprandial glucose, and mean daily IG dose.
Of 464 randomized patients (mean: age 58 years; HbA1c 8.5% [69 mmol/mol]; diabetes duration 11.3 years), 91% completed 28 weeks. Exenatide QW+IG versus placebo+IG significantly reduced HbA1c (least-squares mean difference, −0.73% [−8.0 mmol/mol]; 95% confidence interval, −0.93%, −0.53% [−10.2, −5.8 mmol/mol]; P<.001; final HbA1c, 7.55% [59 mmol/mol] and 8.24% [67 mmol/mol], respectively); body weight (−1.50 kg; −2.17, −0.84; P<.001); and 2-hour postprandial glucose (−1.52 mmol/L [−27.5 mg/dL]; −2.15, −0.90 [−38.7, −16.2]; P<.001). Significantly more exenatide QW+IG- versus placebo+IG-treated patients reached HbA1c <7.0% (<53 mmol/mol) (32.5% vs 7.4%; P<.001); daily IG dose increased by 2 and 4 units, respectively. Gastrointestinal and injection-site adverse events were more frequent with exenatide QW+IG (15.1% and 7.8%, respectively) than with placebo+IG (10.8% and 3.0%); hypoglycaemia incidence was similar between exenatide QW+IG (29.7%) and placebo+IG (29.0%) groups, with no major hypoglycaemic events.
Among patients with inadequate glycaemic control, exenatide QW significantly improved glucose control and decreased body weight, without increased hypoglycaemia or unexpected safety findings. (ClinicalTrials.gov identifier: NCT02229383)