Effect of Efpeglenatide on Cardiovascular Outcomes
Summary
Primary Objective: To demonstrate that efpeglenatide 4 and 6 mg was noninferior to placebo on 3-point major adverse cardiac events (MACE) in Type 2 diabetes mellitus (T2DM) participants at high cardiovascular (CV) risk. Secondary Objectives: To demonstrate that efpeglenatide 4 and 6 mg was superior to placebo in T2DM participants with high CV risk on the following parameters: * 3-point MACE. * Expanded CV outcome. * Composite outcome of new or worsening nephropathy. To assess the safety and tolerability of efpeglenatide 4 and 6 mg, both added to standard of care in T2DM participants at high CV risk.
Timeline
- Start
- 2018-04-27
- Primary completion
- 2020-12-10
- Completion
- 2020-12-10
Outcome
Results reported · no primary-endpoint met/missed verdict (typical of a dose-finding / safety study)
Stopped (Business): “Sponsor decision to cancel TRIAL, not related to safety concern”
registry analysis (non-inferiority test); Efpeglenatide 4 mg+6 mg vs Placebo; p <.0001; Hazard Ratio (HR) 0.732 (95% CI 0.583 to 0.918) NCT03496298 ↗
Publications
- Results Gerstein HC, Sattar N, Rosenstock J, Ramasundarahettige C, Pratley R, Lopes RD, Lam CSP, Khurmi NS, Heenan L, Del Prato S, Dyal L, Branch K; AMPLITUDE-O Trial Investigators. Cardiovascular and Renal Outcomes with Efpeglenatide in Type 2 Diabetes. N Engl J Med. 2021 Sep 2;385(10):896-907. doi: 10.1056/NEJMoa2108269. Epub 2021 Jun 28.
- Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.
- Gerstein HC, Li Z, Ramasundarahettige C, Baek S, Branch KRH, Del Prato S, Lam CSP, Lopes RD, Pratley R, Rosenstock J, Sattar N. Exploring the Relationship Between Efpeglenatide Dose and Cardiovascular Outcomes in Type 2 Diabetes: Insights From the AMPLITUDE-O Trial. Circulation. 2023 Mar 28;147(13):1004-1013. doi: 10.1161/CIRCULATIONAHA.122.063716. Epub 2023 Feb 20.
- Lam CSP, Ramasundarahettige C, Branch KRH, Sattar N, Rosenstock J, Pratley R, Del Prato S, Lopes RD, Niemoeller E, Khurmi NS, Baek S, Gerstein HC. Efpeglenatide and Clinical Outcomes With and Without Concomitant Sodium-Glucose Cotransporter-2 Inhibition Use in Type 2 Diabetes: Exploratory Analysis of the AMPLITUDE-O Trial. Circulation. 2022 Feb 22;145(8):565-574. doi: 10.1161/CIRCULATIONAHA.121.057934. Epub 2021 Nov 14.
- Gerstein HC, Branch K, Heenan L, Del Prato S, Khurmi NS, Lam CSP, Pratley R, Rosenstock J, Sattar N. Design and baseline characteristics of the AMPLITUDE-O cardiovascular outcomes trial of efpeglenatide, a weekly glucagon-like peptide-1 receptor agonist. Diabetes Obes Metab. 2021 Feb;23(2):318-323. doi: 10.1111/dom.14223. Epub 2020 Oct 22.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Efpeglenatide | Peptide | 4 mg | Subcutaneous |
| Subject | Efpeglenatide | Peptide | 6 mg | Subcutaneous |