Key papers ✓ 3? 1

• ✓ Positive human RCTLancet · 2025

  Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial.

  Humans263 peopleRandomizedPlacebo-controlledDouble-blind48 weeks

  Phase 2, multicentre (46 US centres), double-blind, randomised, placebo-controlled dose-ranging trial

  In 263 US adults with obesity/overweight, 48 weeks of eloralintide reduced weight by 9-20% depending on dose vs 0.4% with placebo; nausea (up to 64%) and fatigue (up to 46%) were the most common adverse events.

  Key resultMean bodyweight change (efficacy estimand) ranged from -9% (1 mg) to -20% (9 mg; 95% CI -22.7 to -17.5) vs -0.4% with placebo

  Study details

  Studied

  Adults 18-75 years with obesity (BMI 30 or higher) or overweight (BMI 27 or higher) with a weight-related comorbidity, without type 2 diabetes

  Compared with

  Placebo

  Main outcome

  Percent change in bodyweight from baseline at 48 weeks

  Sample

  263 randomized across six eloralintide arms and placebo

  Authors' conclusion

  Eloralintide produced clinically meaningful, dose-dependent bodyweight reductions over 48 weeks and was generally well tolerated, supporting its potential for obesity treatment.

  Limitations

  Phase 2; funded by Eli Lilly; nausea up to 64% and fatigue up to 46% at some doses.

  DOI 10.1016/S0140-6736(25)02155-5PubMed 41207310
• ✓ Positive meta-analysisEndocrinol Diabetes Metab · 2026

  Novel Amylin-Based Therapies for Weight Management in Adults With Overweight or Obesity Without Diabetes: A Network Meta-Analysis.

  Humans4,642 people6 trials pooledRandomized trials12-68 weeks

  Frequentist random-effects network meta-analysis of RCTs

  Network meta-analysis of 6 trials (4,642 people) estimated high-dose eloralintide at about 18% more weight loss than placebo, with more GI adverse events; authors rate the data as sparse and low-certainty.

  Key resultVersus placebo, high-dose eloralintide mean difference -18.01% (P score 0.89), behind high-dose amycretin (-23.95%) and similar to CagriSema (-17.18%)

  Study details

  Studied

  Adults with overweight or obesity without diabetes in trials of amylin-based therapies

  Compared with

  Placebo or active comparators (semaglutide, liraglutide)

  Main outcome

  Percent change in body weight; GI adverse events

  Sample

  6 trials, N = 4642, 12-68 weeks

  Authors' conclusion

  Novel amylin-based therapies may induce substantial short- to medium-term weight loss but increase GI adverse events; data are sparse and low-certainty, so findings are preliminary.

  Limitations

  Sparse, low-certainty data; indirect comparisons across trials.

  DOI 10.1002/edm2.70247PubMed 42175595Free full text
  FIGURE 2
• ✓ Positive human trialDiabetes Obes Metab · 2026

  Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: Phase 1 proof of concept.

  Humans100 peopleRandomizedPlacebo-controlled12 weeks

  Phase 1, 12-week randomised, placebo-controlled, participant- and investigator-blinded multiple ascending dose study

  In a 12-week phase 1 multiple-dose study in 100 people with obesity/overweight, weight fell 2.6-11.3%; decreased appetite (19%), headache (12%) and fatigue (11%) were most common, GI events infrequent.

  Key resultLeast squares mean body weight reduction across dose groups ranged from 2.6% to 11.3% at Week 12

  Study details

  Studied

  Participants with obesity or overweight (mean age 44 years, 29% female, mean BMI 32.6 kg/m2)

  Compared with

  Placebo

  Main outcome

  Safety, tolerability, pharmacokinetics and body weight

  Sample

  100 participants in 5 multiple ascending dose cohorts

  Authors' conclusion

  Once-weekly eloralintide was well tolerated with minimal GI adverse events and resulted in clinically meaningful weight loss.

  Limitations

  Phase 1, 12-week study.

  DOI 10.1111/dom.70439PubMed 41559929Free full text
• ? Inconclusive human trialMol Metab · 2025

  Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept.

  Humans + animals48 subjectsRandomizedPlacebo-controlledWeek-4 body weight in the phase 1 trial

  Translational package: in vitro receptor assays, rat and monkey studies, and a phase 1 randomized placebo-controlled single-ascending-dose trial (0.04-12 mg)

  Reduced food intake and weight (mainly fat) in obese rats; in a single-dose phase 1 study in 48 healthy people it was mostly well tolerated, with 2.5-4.4% weight loss at 4 weeks at the higher doses.

  Key resultIn the phase 1 trial, week-4 weight change was -2.5% (p < 0.01) with 4 mg and -4.4% (p < 0.001) with 12 mg vs +0.6% with placebo

  Study details

  Studied

  Cell lines, rats, monkeys, and 48 healthy participants (mean BMI 27.5 kg/m2)

  Compared with

  Placebo; cagrilintide in rat taste-avoidance test

  Main outcome

  Receptor selectivity, food intake and body weight, safety

  Sample

  48 healthy participants in the phase 1 single-ascending-dose trial

  Authors' conclusion

  Eloralintide, an AMY1R-selective agonist, may offer a promising new therapeutic with favorable GI tolerability for obesity.

  Limitations

  Single doses and small human cohorts; most evidence is preclinical.

  DOI 10.1016/j.molmet.2025.102271PubMed 41109426Free full text

Reported side effects

• commonNausea (dose-dependent) [ref]
• commonFatigue [ref] [ref]
• commonDecreased appetite [ref]
• commonHeadache [ref]
• uncommonDiarrhea and vomiting [ref] [ref]

Human data cover at most 48 weeks in a few hundred people; no long-term or outcome data yet.

22 registered human trials (15 active)

✓ positive · ✗ negative · ~ mixed · ? inconclusive, judged on each paper's own main outcome. Grades: A strong human evidence → D little or none. Papers and verdicts are drawn from PubMed, Europe PMC and Russian journals (CyberLeninka); not medical advice.