Efpeglenatide

Overview

Efpeglenatide is an investigational, long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist built from a modified exendin-4 component, an immunoglobulin Fc component and a polyethylene-glycol-derived linker. It has been studied in randomized trials for type 2 diabetes, cardiovascular and composite kidney outcomes, and body-weight change.

The evidence is substantial but narrower than the discovery source suggests. AMPLITUDE-O supports a cardiovascular outcome in a defined population with type 2 diabetes and high cardiovascular or kidney risk. It was not a trial of efpeglenatide as treatment for heart failure. Its kidney endpoint combined decreased kidney function with new macroalbuminuria, so the shorthand “renal protection” hides what was actually measured.

Verified identity and structural boundary

WHO Recommended INN List 73 describes efpeglenatide as an exenatide derivative linked to a human IgG4 Fc dimer through a polyethylene-glycol-derived bridge. The identity record displays a modified 39-residue exendin-4 component and two Fc-fragment sequences. FDA GSRS assigns UNII 3M1V5Z2270, classifies the substance as a protein, and identifies its protein type as a fusion protein. FDA also records the development codes HM11260C and the name langlenatide; trial records use SAR439977 and LAPS-Exendin.

This is not adequately represented as one ordinary linear peptide. The WHO definition includes a polymeric poly(oxyethylene) bridge, while the FDA record defines a multicomponent fusion-protein identity. A single sequence, fixed molecular formula and molecular-weight field are therefore withheld rather than manufacturing false precision.

These registry identifiers define the named substance. They do not verify the identity, concentration, purity, sterility or clinical equivalence of an untested product carrying the same label.

Mechanism, pharmacokinetics and scheduling

Efpeglenatide is an exendin-based GLP-1 receptor agonist. The modified exendin component supplies receptor agonism; the Fc and linker architecture is used to extend exposure. Clinical outcome studies evaluate the complete conjugated study product, not the contribution of each component in isolation.

Two randomized phase 2 pharmacokinetic studies reported median time to maximum serum concentration of 72–144 hours after a single dose and 48–120 hours after the final repeated dose. The geometric mean terminal half-life ranged from 135 to 180 hours across the studies.

PeptideGuide's weekly half-life entry is therefore rejected. Weekly and monthly were tested administration schedules; they are not measured half-lives. Protocol amounts, titration, inclusion criteria, monitoring and stopping rules also cannot be converted into a personal protocol.

Evidence map

Glycaemic and body-weight evidence

In the 20-week phase 2 obesity study, 297 adults without diabetes were randomized to efpeglenatide or placebo with a hypocaloric diet. Placebo-adjusted weight reductions ranged from −6.3 kg to −7.2 kg across the investigated efpeglenatide arms. Discontinuation because of adverse events ranged from 5% to 19% with efpeglenatide. The short duration, diet co-intervention and study-product controls remain part of the result.

AMPLITUDE-M tested efpeglenatide monotherapy in type 2 diabetes inadequately controlled with diet and exercise. At week 30, placebo-adjusted least-squares mean HbA1c changes were −0.5, −0.8 and −1.0 percentage points in the three efpeglenatide arms. The two higher arms also showed statistically significant body-weight reductions versus placebo at that time point.

AMPLITUDE-D found the studied efpeglenatide arms non-inferior to dulaglutide 1.5 mg for HbA1c change at week 56, with body-weight reductions of about 3 kg in all groups. AMPLITUDE-L and AMPLITUDE-S reported numerically greater HbA1c and weight reductions than placebo. All three studies were terminated early by the sponsor because of funding, rather than a stated safety or efficacy reason; that truncation must remain visible when interpreting their results.

The completed Korean phase 3 obesity record, NCT06174779, lists 448 actual participants and completion on 13 March 2026, but had no posted results in the checked ClinicalTrials.gov record. It cannot yet validate a sponsor or vendor outcome claim.

Cardiovascular and kidney outcomes

AMPLITUDE-O randomized 4,076 participants with type 2 diabetes and either prior cardiovascular disease or kidney disease plus another cardiovascular risk factor. During a median 1.81 years, a first major adverse cardiovascular event — nonfatal myocardial infarction, nonfatal stroke, or cardiovascular/undetermined-cause death — occurred in 189 of 2,717 (7.0%) efpeglenatide participants and 125 of 1,359 (9.2%) placebo participants. The hazard ratio was 0.73 (95% CI 0.58–0.92); the trial met both its non-inferiority and superiority tests for this primary outcome.

The composite kidney outcome occurred in 353 (13.0%) efpeglenatide participants and 250 (18.4%) placebo participants, hazard ratio 0.68 (95% CI 0.57–0.79). The endpoint combined decreased kidney function or macroalbuminuria. It is evidence for that composite in the enrolled high-risk population, not proof of a general “renal protection” indication.

The AMPLITUDE-O registry record is labelled terminated and states that the sponsor's cancellation decision was not related to a safety concern. Results were nevertheless posted and the main outcome was published. Both facts matter: the registry status should not be recast as a safety failure, while a positive published trial still does not equal marketing authorisation.

AMPLITUDE-O was a cardiovascular-outcomes trial in high-risk type 2 diabetes, not a randomized treatment trial for heart failure. The discovery source's “heart failure management” wording therefore exceeds the protected evidence and is not promoted.

Safety and research limitations

Across the reviewed trials, gastrointestinal events were the most frequent tolerability findings. In AMPLITUDE-O, diarrhea, constipation, nausea, vomiting or bloating occurred more often with efpeglenatide than placebo. AMPLITUDE-M described gastrointestinal events as mostly transient and mild-to-moderate, with few reported hypoglycaemia events in that monotherapy setting. Those study-level findings are not a declaration that the substance is safe for unsupervised use.

The evidence base also has structural limits:

• the major studies used sponsor-defined, monitored investigational products;
• several phase 3 glycaemic studies stopped early for funding reasons;
• AMPLITUDE-O enrolled a particular high-risk type 2 diabetes population;
• its kidney result used a composite that included macroalbuminuria;
• the completed 2026 obesity phase 3 record has no posted results;
• no reviewed source establishes equivalence between a retail research material and the clinical product.

Current programme, regulation, Russian and sport boundaries

A bounded ClinicalTrials.gov query for efpeglenatide, HM11260C or SAR439977 returned 13 records: 7 completed, 4 terminated, 1 recruiting and 1 with unknown status. Five records had posted structured results. The recruiting Korean phase 3 study NCT07379333 is testing HM11260C with metformin and dapagliflozin in type 2 diabetes; a recruiting record is not positive evidence.

The exact-name openFDA approval query returned no match, and the European Commission Union Register dataset contained no efpeglenatide product. This is a bounded FDA and central-EU finding, not a claim that every national register worldwide has been exhausted. A registered substance, a phase 3 trial or a marketing application is not itself approval.

A targeted PubMed query found one Russian-affiliation record, PMID 35126141. It is an English-language international review of antidiabetic drug development, not a Russian direct-administration trial. It is retained as secondary context and does not independently confirm efficacy or safety.

The checked 2026 WADA Prohibited List names neither efpeglenatide nor the codes HM11260C or SAR439977. Exact-name absence is not sport clearance, and no prohibited class is inferred.

Research interpretation

Efpeglenatide has stronger human evidence than a catalog-only research compound: randomized phase 2 and phase 3 trials support glycaemic and short-term weight effects, and AMPLITUDE-O supports a cardiovascular outcome in high-risk type 2 diabetes. The honest conclusion is still bounded. The trial does not transform efpeglenatide into a general heart-failure therapy, the composite kidney result is not a universal kidney indication, and an unreported phase 3 obesity record cannot be counted as positive.

For research use, the first question is identity. The complete registered substance is a PEG-linked exendin/Fc fusion construct, not just a generic “long-acting peptide.” Without analytical confirmation, a material sold under the name cannot inherit the evidence of the defined clinical product.