Efpeglenatide

Key findings (each cites a source)

• In a randomized, placebo-controlled trial (AMPLITUDE-O) in participants with type 2 diabetes and either prior cardiovascular disease or current kidney disease plus at least one additional cardiovascular risk factor, a major adverse cardiovascular event (MACE) occurred less often with efpeglenatide than with placebo over a median follow-up of 1.81 years (hazard ratio 0.73; 95% CI 0.58 to 0.92). (PMIDs: 34215025) [PMID 34215025]
• In the same AMPLITUDE-O trial, a composite renal outcome event occurred less often with efpeglenatide than with placebo (hazard ratio 0.68; 95% CI 0.57 to 0.79). (PMIDs: 34215025) [PMID 34215025]
• In AMPLITUDE-O, gastrointestinal adverse events (diarrhea, constipation, nausea, vomiting, or bloating) were reported more frequently with efpeglenatide than with placebo. (PMIDs: 34215025) [PMID 34215025]
• The AMPLITUDE-O trial design described recruiting 4076 participants across 344 sites in 28 countries and defined a primary major adverse cardiovascular event composite (non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death) and a secondary composite kidney outcome. (PMIDs: 33026143) [PMID 33026143]
• In AMPLITUDE-M, a phase 3, double-blind, placebo-controlled trial in type 2 diabetes inadequately controlled with diet and exercise alone, efpeglenatide (2, 4, and 6 mg) produced statistically superior HbA1c reductions versus placebo at week 30, along with reported weight and fasting plasma glucose improvements (with gastrointestinal adverse events described as most commonly reported). (PMIDs: 35671039) [PMID 35671039]
• A meta-analysis of randomized controlled trials evaluating efpeglenatide in type 2 diabetes reported that efpeglenatide lowered HbA1c, body weight, and fasting serum glucose versus control, while gastrointestinal adverse events were significantly higher in the efpeglenatide group than in controls. (PMIDs: 37885518) [PMID 37885518]
• A systematic review and meta-analysis of 21 randomized controlled trials (99,599 patients) reported that GLP-1 receptor agonists (including efpeglenatide) reduced trial-defined MACE and other mortality outcomes versus controls, with increased gastrointestinal and gallbladder disorders reported and no differences in stroke, pancreatitis, or neoplasm reported. (PMIDs: 40892610) [PMID 40892610]
• A meta-analysis of cardiovascular outcome trials in type 2 diabetes reported that GLP-1 receptor agonists reduced MACE, cardiovascular death, nonfatal stroke, hospitalization for heart failure, all-cause mortality, and a broad composite kidney outcome driven by reduced macroalbuminuria (not specifically isolating efpeglenatide). (PMIDs: 34526024) [PMID 34526024]
• A review described efpeglenatide among GLP-1 receptor agonists discussed in the context of pleiotropic effects in metabolic dysfunction-associated steatohepatitis (MASLD/MASH), stating that phase I–III trials are associated with clinically relevant hepatic improvements including MASH resolution, liver fat reduction, and preventing worsening fibrosis (as described within that review). (PMIDs: 40016997) [PMID 40016997]
• A network meta-analysis review reported comparative findings across multiple GLP-1 receptor agonists and stated that, within that analysis, efpeglenatide was the most effective in reducing major adverse cardiovascular events (with interpretive caution due to study limitations). (PMIDs: 39910752) [PMID 39910752]