Indication assessment · §2
Obesity and overweight in adults — evidence across compounds
Every compound the Institute assesses in obesity and overweight in adults, with its certainty rating.
§2Evidence across compounds
Every compound the Institute assesses in this indication, with the effect as recorded, the certainty rating and the contributing trials. Effects are reported on the anchor outcome where the contributing trials measured it and on the outcome the trial actually reported where they did not.
Table 1. Compounds assessed in obesity and overweight in adults, ordered by certainty.
| Compound | Effect as recorded | Interval as reported | Certainty | Trials |
|---|---|---|---|---|
| LiraglutideGLP-1 receptor agonist (acylated, once-daily) | −8.0 % body weight at 56 weeks with 3.0 mg versus −2.6 % with placebo | estimated difference −5.4 percentage points (95 % CI −5.8 to −5.0) | High | 2 |
| SemaglutideGLP-1 receptor agonist (acylated, long-acting) | −14.9 % body weight at 68 weeks with semaglutide 2.4 mg versus −2.4 % with placebo | treatment difference −12.4 percentage points (95 % CI −13.4 to −11.5) | High | 5 |
| TirzepatideDual GIP and GLP-1 receptor agonist (acylated) | −20.9 % body weight at 72 weeks with 15 mg versus −3.1 % with placebo (SURMOUNT-1) | treatment difference −17.8 percentage points (95 % CI −19.3 to −16.3) | High | 5 |
| AOD-9604Growth-hormone C-terminal fragment analogue | A 12-week phase 2b trial in 300 participants did not demonstrate a statistically significant difference in body weight versus placebo at any dose | negative result | Moderate | 1 |
| CagrilintideLong-acting amylin and calcitonin receptor agonist… | −10.8 % body weight at 26 weeks with cagrilintide 4.5 mg monotherapy versus −3.0 % with placebo, and −8.6 % with liraglutide 3.0 mg as active reference | estimated difference versus placebo −7.8 percentage points (95 % CI −10.2 to −5.4) | Moderate | 2 |
| CagriSema (cagrilintide with semaglutide)Fixed-ratio combination of a long-acting amylin analogue… | −22.7 % body weight at 68 weeks versus −2.3 % with placebo in adults with obesity without diabetes | estimated difference −20.4 percentage points (95 % CI −21.7 to −19.1) | Moderate | 3 |
| DulaglutideGLP-1 receptor agonist, Fc-fusion protein | −4.6 kg at 4.5 mg over 52 weeks in type 2 diabetes | difference versus 1.5 mg −1.9 kg (95 % CI −2.4 to −1.4) | Moderate | 1 |
| ExenatideGLP-1 receptor agonist (exendin-based, short- and… | −2.3 to −3.6 kg | modest | Moderate | 1 |
| LixisenatideGLP-1 receptor agonist (exendin-based, short-acting) | −1.8 to −2.7 kg | modest | Moderate | 1 |
| MazdutideDual glucagon and GLP-1 receptor agonist (oxyntomodulin… | −14.4 % body weight at 48 weeks with 6 mg in a Chinese phase 3 trial versus −0.3 % with placebo | estimated difference −14.1 percentage points (95 % CI −15.7 to −12.5) | Moderate | 3 |
| OrforglipronOral non-peptide GLP-1 receptor partial agonist | −14.7 % body weight at 36 weeks with 45 mg in the phase 2 trial versus −2.3 % with placebo | estimated difference −12.4 percentage points (95 % CI −14.8 to −10.0) | Moderate | 3 |
| RetatrutideTriple GIP, GLP-1 and glucagon receptor agonist (acylated) | −24.2 % body weight at 48 weeks with 12 mg in the phase 2 trial versus −2.1 % with placebo | least-squares mean difference −22.1 percentage points (95 % CI −25.0 to −19.2) | Moderate | 3 |
| Semaglutide, oralGLP-1 receptor agonist, oral formulation with absorption… | −15.1 % body weight with oral 50 mg at 68 weeks versus −2.4 % with placebo | estimated difference −12.7 percentage points (95 % CI −14.2 to −11.3) | Moderate | 1 |
| SurvodutideDual glucagon and GLP-1 receptor agonist (acylated) | −14.9 % body weight at 46 weeks with 6.0 mg in phase 2 versus −2.8 % with placebo | estimated difference −12.1 percentage points (95 % CI −15.4 to −8.8) | Moderate | 3 |
| AmycretinUnimolecular amylin and GLP-1 receptor co-agonist | −13.1 % body weight at 12 weeks in a phase 1b subcutaneous study versus −1.1 % with placebo | phase 1b; very small sample | Low | 3 |
| DanuglipronOral non-peptide GLP-1 receptor agonist | −8.0 to −13.0 % body weight at 32 weeks across doses, with discontinuation rates above 50 % in some arms | wide; high attrition compromises the estimate | Low | 1 |
| EcnoglutideGLP-1 receptor agonist (cAMP-biased, acylated) | −13.2 % body weight at 48 weeks with the highest dose versus −0.5 % with placebo in a Chinese phase 3 trial | estimated difference −12.7 percentage points (95 % CI −14.5 to −10.9) | Low | 1 |
| Maridebart cafraglutideGIP receptor antagonist and GLP-1 receptor agonist… | −16.2 % body weight at 52 weeks at the highest dose in phase 2 versus −2.5 % with placebo | estimated difference −13.7 percentage points (95 % CI −17.1 to −10.3) | Low | 2 |
| PetrelintideLong-acting amylin analogue | −8.6 % body weight at 16 weeks in a phase 1b multiple-ascending-dose study versus −1.7 % with placebo | small sample; confidence limits wide | Low | 2 |
| PramlintideAmylin analogue, short-acting | −3.7 kg at 16 weeks versus placebo in a non-diabetic obesity study | modest | Low | 1 |
| 5-amino-1MQSmall-molecule nicotinamide N-methyltransferase inhibitor | No human trial of any kind identified | — | Very low | 0 |
| Melanotan-IINon-selective melanocortin receptor agonist (cyclic… | No randomised trial identified | — | Very low | 0 |
| MOTS-cMitochondrial-derived 16-residue peptide | No randomised controlled human trial identified | — | Very low | 0 |
| Estimates in this table are not on a common scale and must not be subtracted from one another. Where a comparison between two compounds has been made directly, it appears in a synthesis and not here. | ||||
Moderate or high certaintyLow or very low certainty
§2.1Syntheses bearing on this indication
- Glucagon-like peptide-1 receptor agonists for weight reduction in adults with obesity — High
- Dual and triple incretin receptor agonists compared with single glucagon-like peptide-1 receptor agonists for weight… — Moderate
- Weight change after discontinuation of an incretin receptor agonist — Moderate
- Gastrointestinal adverse events with incretin receptor agonists — High
- Change in lean mass during pharmacologically induced weight reduction — Low
- Oral compared with injectable presentations of glucagon-like peptide-1 receptor agonism — Moderate
- Percentage weight change as a surrogate outcome — Low
- Amylin analogues as monotherapy and in combination — Moderate
- Distribution of access to obesity pharmacotherapy — Low
- Transitivity in the incretin network — Moderate
- Tirzepatide in obesity and overweight in adults: effect on the anchor outcome — High
- Semaglutide in obesity and overweight in adults: effect on the anchor outcome — High
- Retatrutide in obesity and overweight in adults: effect on the anchor outcome — Moderate
- CagriSema (cagrilintide with semaglutide) in obesity and overweight in adults: effect on the anchor outcome — Moderate
- Survodutide in obesity and overweight in adults: effect on the anchor outcome — Moderate
- Liraglutide in obesity and overweight in adults: effect on the anchor outcome — High
- Mazdutide in obesity and overweight in adults: effect on the anchor outcome — Moderate
- Orforglipron in obesity and overweight in adults: effect on the anchor outcome — Moderate
- Maridebart cafraglutide in obesity and overweight in adults: effect on the anchor outcome — Low
- Petrelintide in obesity and overweight in adults: effect on the anchor outcome — Low
- Tirzepatide in obesity and overweight in adults: tolerability and discontinuation — High
- Semaglutide in obesity and overweight in adults: tolerability and discontinuation — High
- Retatrutide in obesity and overweight in adults: tolerability and discontinuation — Moderate
- CagriSema (cagrilintide with semaglutide) in obesity and overweight in adults: tolerability and discontinuation — Moderate
- Survodutide in obesity and overweight in adults: tolerability and discontinuation — Moderate
- Liraglutide in obesity and overweight in adults: tolerability and discontinuation — High
- Mazdutide in obesity and overweight in adults: tolerability and discontinuation — Moderate
- Orforglipron in obesity and overweight in adults: tolerability and discontinuation — Moderate
- Maridebart cafraglutide in obesity and overweight in adults: tolerability and discontinuation — Low
- Petrelintide in obesity and overweight in adults: tolerability and discontinuation — Low
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, Lau DCW, le Roux CW, Violante Ortiz R, Jensen CB, Wilding JPH. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. New England Journal of Medicine 2015;373(1):11–22. doi:10.1056/NEJMoa1411892 · PMID 26132939
- Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JFE, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB. Liraglutide and cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine 2016;375(4):311–322. doi:10.1056/NEJMoa1603827 · PMID 27295427
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.
Compound Evidence Institute · CEI-IN-01/2 · https://compoundevidence.com/indications/obesity/evidence/ · retrieved 30 July 2026