TY - JOUR
T1 - Efficacy and safety of once-weekly efpeglenatide in people with suboptimally controlled type 2 diabetes
T2 - The AMPLITUDE-D, AMPLITUDE-L and AMPLITUDE-S randomized controlled trials
AU - Aroda, Vanita R.
AU - Frias, Juan Pablo
AU - Ji, Linong
AU - Niemoeller, Elisabeth
AU - Nguyên-Pascal, My Liên
AU - Denkel, Karl
AU - Espinasse, Melanie
AU - Guo, Hailing
AU - Baek, Seung Jae
AU - Choi, Jae Duk
AU - Lingvay, Ildiko
N1 - Publisher Copyright:
© 2023 John Wiley & Sons Ltd.
PY - 2023/8
Y1 - 2023/8
N2 - 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.
AB - 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.
KW - GLP-1 receptor analogue
KW - dulaglutide
KW - efpeglenatide
KW - glycaemic control
KW - type 2 diabetes
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U2 - 10.1111/dom.15079
DO - 10.1111/dom.15079
M3 - Article
C2 - 37013892
AN - SCOPUS:85153614489
SN - 1462-8902
VL - 25
SP - 2084
EP - 2095
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - 8
ER -