Efficacy and safety of once-weekly efpeglenatide in people with suboptimally controlled type 2 diabetes: The AMPLITUDE-D, AMPLITUDE-L and AMPLITUDE-S randomized controlled trials

Aim To evaluate the efficacy and safety of once-weekly (QW) efpeglenatide in people with type 2 diabetes (T2D) suboptimally controlled with oral glucose-lowering drugs and/or basal insulin (BI).Materials and Methods Three phase 3, multicentre, randomized controlled trials compared the efficacy and safety of QW efpeglenatide versus dulaglutide when added to metformin (AMPLITUDE-D), efpeglenatide versus placebo when added to BI +/- oral glucose-lowering drugs (AMPLITUDE-L) or metformin +/- sulphonylurea (AMPLITUDE-S). All trials were terminated early by the sponsor because of funding rather than safety or efficacy concerns.Results In AMPLITUDE-D, non-inferiority of efpeglenatide to dulaglutide 1.5 mg was shown in HbA1c reduction from baseline to week 56, least squares mean treatment difference (95% CI): 4 mg, -0.03% (-0.20%, 0.14%)/-0.35 mmol/mol (-2.20, 1.49); 6 mg, -0.08% (-0.25%, 0.09%)/-0.90 mmol/mol (-2.76, 0.96). The reductions in body weight (approximately 3 kg) from baseline to week 56 were similar across all treatment groups. In AMPLITUDE-L and AMPLITUDE-S, numerically greater reduction in HbA1c and body weight were observed at all doses of efpeglenatide than placebo. American Diabetes Association level 2 hypoglycaemia (< 54 mg/dL [< 3.0 mmol/L]) was reported in few participants across all treatment groups (AMPLITUDE-D, = 1%; AMPLITUDE-L, = 10%; and AMPLITUDE-S, = 4%). The adverse events profile was consistent with other glucagon-like peptide-1 receptor agonists (GLP-1 RAs); gastrointestinal adverse events were most frequent in all three studies.Conclusions In people with T2D suboptimally controlled with oral glucose-lowering drugs and/or BI, QW efpeglenatide was non-inferior to dulaglutide in terms of HbA1c reduction and showed numerically greater improvements than placebo in glycaemic control and body weight, with safety consistent with the GLP-1 RA class.