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

Abstract 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.