Amylin and Incretin Peptides: 2026 Human Evidence Map
A trial-by-trial look at zenagamtide, eloralintide, petrelintide, VK2735, and CagriSema, with populations, duration, outcomes, safety signals, and evidence limits.
Amylin-pathway peptides and combined incretin agonists have produced weight-change signals in human trials, but the programs are at different stages. Zenagamtide, eloralintide, petrelintide, and VK2735 remain investigational in the United States at this review. CagriSema has published phase 3 results, yet those results should not be treated as an FDA-approved label. This evidence map uses original study reports available through September 30, 2026.
First separate the mechanisms
Amylin is a pancreatic peptide hormone involved in meal-related satiety and gastric signaling. Eloralintide and petrelintide pursue the amylin pathway. GLP-1 and GIP are separate incretin pathways. VK2735 combines GIP and GLP-1 receptor agonism. Zenagamtide is a single molecule with GLP-1 and amylin receptor activity, while CagriSema combines two molecules, cagrilintide and semaglutide. A shared weight-management target does not make these products pharmacologically interchangeable.
What the human studies actually report
| Program and source | Studied population and design | Duration | Reported result | Boundary |
|---|---|---|---|---|
| Zenagamtide (amycretin) | 125 adults with overweight or obesity, without diabetes; randomized phase 1b/2a injectable study | 36 weeks | Estimated mean weight change of −24.3% in the 60 mg cohort vs −1.1% placebo | Early, multi-cohort study with withdrawals; this is not a direct comparison with marketed drugs or evidence for the oral form. |
| Eloralintide | 100 participants; randomized phase 1 proof of concept with multiple cohorts | 12 weeks | Least-squares mean weight reductions of 2.6%–11.3% across active cohorts | A range across regimens is not one pooled treatment effect; duration is short. |
| Petrelintide | Two randomized, controlled phase 1 studies | 16 weeks for the cited maximum | Up to 8.6% weight reduction; approximately 10-day half-life reported | Maximum result and pharmacokinetics are early-phase findings, not an approved product profile. |
| VK2735, VENTURE | 175 adults with obesity or overweight plus a related condition; diabetes excluded; randomized phase 2 dose-ranging study | 13 weeks | 9.1%–14.7% mean weight reductions across active groups vs 1.7% placebo | Dose-ranging and short follow-up; gastrointestinal adverse events were common. |
| CagriSema, REDEFINE 1 | Adults with obesity or overweight plus a related condition, without diabetes; phase 3 | 68 weeks | −20.4% with CagriSema vs −3.0% placebo under the treatment-policy estimand | Longer, later-stage evidence, but still not a head-to-head comparison with the programs above. |
| CagriSema, REDEFINE 2 | Adults with overweight or obesity and type 2 diabetes; phase 3 | 68 weeks | −13.7% vs −3.4% placebo mean weight change | The diabetes population and trial design differ from REDEFINE 1. |
The numbers cannot be ordered into a drug “leaderboard.” Trial duration ranges from 12 to 68 weeks, baseline populations differ, and study estimands, dose escalation, missing-data handling, and placebo response affect the reported averages. Only a direct randomized comparison can support a narrow comparative claim about the regimens and population it studied.
Safety evidence is still uneven
The eloralintide phase 1 report noted nausea in 8% of exposed participants. VENTURE described predominantly gastrointestinal adverse events with VK2735. Those observations should not be converted into a claim that one molecule is “gentler” than another: the trials used different populations, durations, doses, and adverse-event collection. The phase 1 studies are especially limited for uncommon or delayed harms. For an approved drug, consult the exact FDA product label rather than transferring a safety statement between molecules.
What would change the evidence assessment
A stronger assessment needs longer randomized studies with a prespecified comparator, retention and missing-data details, reported serious adverse events, and outcomes beyond a short weight-change window. An FDA decision would add a product-specific benefit-risk review and label. A sponsor topline release or registry status can guide what to watch next, but neither replaces a full original report.
For approved incretin products and the limits of direct versus indirect comparisons, see Semaglutide vs Tirzepatide and Newer Incretin Agonists. For dated status changes, see Research Alerts.