Efficacy and Safety of Once-Weekly Efpeglenatide Monotherapy Versus Placebo in Type 2 Diabetes: The AMPLITUDE-M Randomized Controlled Trial

Abstract

Objective: To assess the efficacy and safety of the glucagon-like peptide 1 receptor agonist (GLP-1 RA) efpeglenatide versus placebo in patients with type 2 diabetes inadequately controlled with diet and exercise alone.

Research design and methods: AMPLITUDE-M was a phase 3, double-blind, placebo-controlled, multicenter trial that randomized adults with type 2 diabetes suboptimally controlled with diet and exercise alone to once-weekly efpeglenatide (2, 4, or 6 mg) or placebo for up to 56 weeks. The primary objective was to demonstrate the superiority of efpeglenatide versus placebo for HbA1c reduction at week 30. Secondary objectives included changes in other measures of glycemic control and body weight at weeks 30 and 56.

Results: At week 30, HbA1c was reduced from a baseline of 8.1% (65 mmol/mol) to 6.9% (52 mmol/mol), 6.6% (49 mmol/mol), and 6.4% (47 mmol/mol) with efpeglenatide 2, 4, and 6 mg, respectively. Least squares mean HbA1c reductions from baseline were statistically superior for each efpeglenatide dose versus placebo (2 mg, -0.5% [95% CI -0.9, -0.2; P = 0.0054]; 4 mg, -0.8% [-1.2, -0.5; P < 0.0001]; 6 mg, -1.0% [-1.4, -0.7; P < 0.0001]). A greater proportion of efpeglenatide-treated patients (all doses) achieved HbA1c <7% (53 mmol/mol) versus placebo by week 30 (P < 0.0001 for all), and significant reductions in body weight and fasting plasma glucose were also observed for efpeglenatide (4 and 6 mg doses) versus placebo at week 30 (P < 0.05 for all). Consistent with the GLP-1 RA class, gastrointestinal adverse events were most commonly reported; these were generally transient and mild/moderate in severity. Few patients reported hypoglycemia.

Conclusions: As monotherapy in patients with type 2 diabetes, once-weekly efpeglenatide significantly improved glycemic control and body weight with a safety and tolerability profile similar to that of other GLP-1 RAs.

Trial registration: ClinicalTrials.gov NCT03353350.

© 2022 by the American Diabetes Association.

Figures

Figure 1

Mean change in HbA1c over time.

Figure 2

Secondary efficacy end points: proportion of patients achieving HbA1c targets (A), LS mean ± SE change in FPG (B), and LS mean change in body weight (C) for each dose group vs. placebo from baseline to weeks 30 and 56. FPG, fasting plasma glucose; LS, least squares; SD, standard deviation; SE, standard error.