weight-loss

Aleniglipron INVESTIGATIONAL

weight-loss Decrease

Moderate evidence

Oral non-peptide GLP-1RA (GSBR-1290, Structure Therapeutics). In ACCESS phase 2b (230 adults, obesity/overweight), once-daily aleniglipron at 45/90/120 mg achieved...

Structure Therapeutics press (ACCESS, ACCESS II, 2025-2026); Nature Medicine ACCESS phase... Source

Full findingOral non-peptide GLP-1RA (GSBR-1290, Structure Therapeutics). In ACCESS phase 2b (230 adults, obesity/overweight), once-daily aleniglipron at 45/90/120 mg achieved placebo-adjusted weight loss of -8.2/-9.8/-11.3% at week 36. ACCESS II topline reported placebo-adjusted mean weight loss of 16.3% at the 180 mg dose at 44 weeks - described by the sponsor as the highest weight loss for an oral GLP-1RA to date.

PopulationACCESS phase 2b: 230 adults obesity/overweight, once-daily, 36 wk, placebo-controlled. ACCESS II: phase 2, up to 180 mg, 44 wk

Fundingindustry - Structure Therapeutics (sponsor of record; disclosed)

Comparatorsplacebo

BI 3034701 INVESTIGATIONAL

weight-loss Decrease

Very low evidence

BI 3034701 (Boehringer Ingelheim / Gubra) is an investigational, potential first-in-class triple GLP-1 / GIP / NPY2 receptor agonist peptide for obesity. The phase 1...

Boehringer Ingelheim / Gubra press releases (phase 1 start 2024; phase 2 advance 2026) Source

Full findingBI 3034701 (Boehringer Ingelheim / Gubra) is an investigational, potential first-in-class triple GLP-1 / GIP / NPY2 receptor agonist peptide for obesity. The phase 1 first-in-human trial demonstrated a favourable safety/tolerability profile and showed encouraging weight loss; Boehringer plans to initiate phase 2 in mid-2026.

PopulationPhase 1 (NCT06352437): randomised first-in-human placebo-controlled, two parts - Part A healthy men 18-55; Part B adults 18-65 with overweight/obesity otherwise healthy; ~124 participants; completed H2 2025

Fundingindustry (company press release on own pipeline)

Comparatorsplacebo

Cagrilintide INVESTIGATIONAL

weight-loss Decrease

Moderate evidence

Once-weekly cagrilintide monotherapy produced dose-dependent weight loss in adults with overweight/obesity; 4.5 mg gave ~10.8% (~11.5 kg) at 26 weeks vs ~3.0% placebo,...

Lau et al., Lancet 2021 (phase 2); Novo Nordisk REDEFINE 1, NEJM 2025 Source

Full findingOnce-weekly cagrilintide monotherapy produced dose-dependent weight loss in adults with overweight/obesity; 4.5 mg gave ~10.8% (~11.5 kg) at 26 weeks vs ~3.0% placebo, curves not plateaued. As a 2.4 mg monotherapy arm within REDEFINE 1 (68 wk, T2D-free), cagrilintide alone gave 11.5% mean weight reduction.

Populationphase 2: adults overweight/obesity, 0.3-4.5 mg, 26 wk, placebo-controlled; REDEFINE 1: cagrilintide 2.4 mg arm within 3,417 adults, 68 wk

Fundingindustry - Novo Nordisk

Comparatorsplacebo; liraglutide 3.0 mg (phase 2); semaglutide 2.4 mg (REDEFINE 1); CagriSema (REDEFINE 1)

CagriSema INVESTIGATIONAL

weight-loss Decrease

High evidence

In phase 3 REDEFINE 1, once-weekly CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg) gave 22.7% mean weight reduction at 68 weeks vs 3% placebo in...

Coadministered Cagrilintide and Semaglutide in Overweight/Obesity, NEJM 2025 (REDEFINE 1)... Source

Full findingIn phase 3 REDEFINE 1, once-weekly CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg) gave 22.7% mean weight reduction at 68 weeks vs 3% placebo in overweight/obesity without T2D (efficacy estimand; treatment-policy ~20.4%). 40.4% reached >=25% weight loss (vs 16.2% sema, 6.0% cagrilintide, 0.9% placebo); 88% with prediabetes returned to normoglycaemia. As reported, the 22.7% fell short of the company's pre-trial ~25% expectation, prompting commentary that the result underwhelmed expectations.

PopulationREDEFINE 1: 3,417 adults obesity/overweight + >=1 comorbidity, no T2D; 68 wk; randomised 21:3:3:7 CagriSema:semaglutide:cagrilintide:placebo

Fundingindustry - Novo Nordisk

Comparatorsplacebo; semaglutide 2.4 mg; cagrilintide 2.4 mg

Enicepatide INVESTIGATIONAL

weight-loss Decrease

Very low evidence

CT-388 (Roche/Genentech, ex-Carmot) is a once-weekly subcutaneous GLP-1/GIP dual agonist. In a phase 2 obesity trial it achieved a statistically significant...

Roche/Genentech phase 2 topline, Jan 2026; earlier phase 1b (Applied Clinical Trials) Source

Full findingCT-388 (Roche/Genentech, ex-Carmot) is a once-weekly subcutaneous GLP-1/GIP dual agonist. In a phase 2 obesity trial it achieved a statistically significant placebo-adjusted weight loss of 22.5% at 48 weeks at the highest dose (24 mg), without reaching a plateau; 87% of the 24 mg group achieved >=10% and 47.8% >=20% weight loss, and 54% reached BMI <30 (vs 13% placebo).

PopulationPhase 2: 469 adults with obesity or overweight + >=1 comorbidity, dose-escalation up to 24 mg once-weekly s.c., 48 weeks, randomised double-blind placebo-controlled

Fundingindustry - Roche (trial sponsor; inferred from registration trial)

Comparatorsplacebo

Dulaglutide MARKETED

weight-loss Mixed

Moderate evidence

In AWARD-1 (type 2 diabetes on metformin plus pioglitazone), dulaglutide produced modest weight change against a weight-gaining background regimen, with the 1.5 mg...

Wysham C, Blevins T, Arakaki R, et al. Efficacy and safety of dulaglutide added onto piog... Source

Full findingIn AWARD-1 (type 2 diabetes on metformin plus pioglitazone), dulaglutide produced modest weight change against a weight-gaining background regimen, with the 1.5 mg dose giving near-neutral weight and 0.75 mg a small gain.

PopulationAWARD-1: phase-3 parallel-arm randomised trial, N=976; type 2 diabetes on metformin + pioglitazone; 52 weeks; comparators placebo (double-blind) and exenatide (OPEN-LABEL active comparator).

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Comparatorsplacebo; exenatide

Dulaglutide MARKETED

weight-loss Decrease

High evidence

In AWARD-3, weight change with dulaglutide on a metformin-comparator monotherapy background was similar to metformin for the 1.5 mg dose and smaller (less loss) for...

Umpierrez G, Tofe Povedano S, Perez Manghi F, et al. Efficacy and safety of dulaglutide m... Source

Full findingIn AWARD-3, weight change with dulaglutide on a metformin-comparator monotherapy background was similar to metformin for the 1.5 mg dose and smaller (less loss) for 0.75 mg.

PopulationAWARD-3: 52-week double-blind randomised trial, N=807; early type 2 diabetes; dulaglutide 1.5/0.75 mg vs metformin monotherapy.

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Comparatorsmetformin

Dulaglutide MARKETED

weight-loss Decrease

Moderate evidence

In AWARD-6, once-weekly dulaglutide 1.5 mg and once-daily liraglutide 1.8 mg produced broadly similar weight reduction over 26 weeks, with liraglutide numerically...

Dungan KM, Povedano ST, Forst T, et al. Once-weekly dulaglutide versus once-daily liraglu... Source

Full findingIn AWARD-6, once-weekly dulaglutide 1.5 mg and once-daily liraglutide 1.8 mg produced broadly similar weight reduction over 26 weeks, with liraglutide numerically slightly greater.

PopulationAWARD-6: phase-3 open-label non-inferiority trial, N=599; metformin-treated type 2 diabetes; dulaglutide 1.5 mg weekly vs liraglutide 1.8 mg daily; 26 weeks.

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Comparatorsliraglutide

Dulaglutide MARKETED

weight-loss Decrease

High evidence

In AWARD-9, dulaglutide added to titrated insulin glargine produced weight loss whereas placebo plus glargine produced weight gain.

Pozzilli P, Norwood P, Jodar E, et al. Placebo-controlled, randomized trial of the additi... Source

PopulationAWARD-9: phase-3 double-blind placebo-controlled randomised trial, N=300; type 2 diabetes on titrated glargine; dulaglutide 1.5 mg vs placebo; 28 weeks.

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Comparatorsplacebo

Elecoglipron INVESTIGATIONAL

weight-loss Decrease

Very low evidence

Oral non-peptide GLP-1RA (ECC5004/AZD5004; INN elecoglipron), discovered by Eccogene, licensed to AstraZeneca. US phase 1 reported clinically meaningful weight...

Eccogene/AstraZeneca press (license Nov 2023; phase 1b topline Feb 2026) Source

Full findingOral non-peptide GLP-1RA (ECC5004/AZD5004; INN elecoglipron), discovered by Eccogene, licensed to AstraZeneca. US phase 1 reported clinically meaningful weight reductions regardless of T2D status plus glycaemic improvements in T2D. Eccogene reported positive topline phase 1b (China, Feb 2026). Advanced to phase 2b: VISTA (obesity), SOLSTICE (T2D).

PopulationPhase 1 (US) and phase 1b (China) in adults with obesity/overweight +/- T2D; phase 2b VISTA/SOLSTICE ongoing

Fundingindustry (company press release on own pipeline)

Comparatorsplacebo

HM15275 INVESTIGATIONAL

weight-loss Decrease

Very low evidence

HM15275 (Hanmi) is a once-weekly long-acting GLP-1/GIP/glucagon triple agonist engineered for obesity, designed to optimise receptor-activity balance to deliver weight...

Hanmi Pharmaceutical, ADA 2025 poster 774-P and ObesityWeek 2025 / company press Source

Full findingHM15275 (Hanmi) is a once-weekly long-acting GLP-1/GIP/glucagon triple agonist engineered for obesity, designed to optimise receptor-activity balance to deliver weight loss while minimising lean-mass loss. Phase 1 reported favourable safety and early weight loss; FDA-cleared for phase 2, which is under way.

PopulationPhase 1: adults, ~4-week early readout, safety/PK/PD. Phase 2 initiated H2 2025. Preclinical efficacy in rodent obesity models.

Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)

Comparatorsplacebo

Liraglutide MARKETED

weight-loss Decrease

High evidence

Once-daily subcutaneous liraglutide 3.0 mg produced a mean weight loss of -8.0% (-8.4 kg) vs -2.6% (-2.8 kg) placebo at week 56; 63.2% achieved >=5% weight loss vs...

Pi-Sunyer X et al., NEJM 2015 (SCALE Obesity and Prediabetes) Source

Full findingOnce-daily subcutaneous liraglutide 3.0 mg produced a mean weight loss of -8.0% (-8.4 kg) vs -2.6% (-2.8 kg) placebo at week 56; 63.2% achieved >=5% weight loss vs 27.1% placebo.

PopulationSCALE Obesity and Prediabetes: 3731 adults without T2D, BMI >=30 (or >=27 with comorbidity), 56 weeks, randomised 2:1 double-blind vs placebo

Fundingindustry-Novo Nordisk

Comparatorsplacebo

MariTide INVESTIGATIONAL

weight-loss Decrease

Very low evidence

Maridebart cafraglutide (MariTide; formerly AMG 133) is a peptide-antibody conjugate that ANTAGONISES the GIP receptor while AGONISING the GLP-1 receptor; half-life...

Amgen, Phase 2 MariTide presented at ADA 85th Scientific Sessions 2025; earlier topline N... Source

Full findingMaridebart cafraglutide (MariTide; formerly AMG 133) is a peptide-antibody conjugate that ANTAGONISES the GIP receptor while AGONISING the GLP-1 receptor; half-life ~21 days. In phase 2 (NEJM 2025), mean weight change at 52 weeks was -12.3% to -16.2% in obesity without T2D (vs -2.5% placebo) and -8.4% to -12.3% in T2D (vs -1.7% placebo) on the treatment-policy (ITT) estimand, with weight loss not plateaued by 52 weeks. HbA1c fell 1.2 to 1.6 percentage points in the T2D cohort.

PopulationPhase 2 (NCT05669599): N=592. Cohort A obesity no T2D (n=465); Cohort B obesity with T2D (n=127). Monthly fixed doses 140/280/420 mg + 8-week 420 mg arm vs placebo; 52 wk

Fundingindustry (company press release on own pipeline)

Comparatorsplacebo

Mazdutide MARKETED

weight-loss Decrease

Moderate evidence

In the registrational Chinese phase-3, the GLP-1/glucagon dual agonist mazdutide produced 11-14% weight loss with low (~1%) discontinuation.

Mazdutide in Chinese adults with obesity (GLORY-1), NEJM 2025 Source

PopulationGLORY-1 (NCT05607680): 610 Chinese adults with obesity or overweight (BMI >=28, or 24-<28 plus a weight-related condition), mazdutide 4/6 mg vs placebo 1:1:1; 48-week phase-3 randomised double-blind placebo-controlled RCT.

FundingInnovent Biologics

Monlunabant INVESTIGATIONAL

weight-loss Decrease

Moderate evidence

In adults with obesity and metabolic syndrome, once-daily oral monlunabant 10 mg gave 7.1 kg weight loss vs 0.7 kg placebo at 16 weeks. Higher doses (20, 50 mg) showed...

Knop et al., Lancet Diabetes Endocrinol 2025; Novo Nordisk press 2024-09-20 Source

Full findingIn adults with obesity and metabolic syndrome, once-daily oral monlunabant 10 mg gave 7.1 kg weight loss vs 0.7 kg placebo at 16 weeks. Higher doses (20, 50 mg) showed dose-dependent withdrawals driven by neuropsychiatric/GI adverse events.

PopulationPhase 2a, N=243, 16 wk, randomised double-blind placebo-controlled dose-ranging (10/20/50 mg), 25 centres Canada; adults obesity + metabolic syndrome

Fundingindustry - Novo Nordisk (disclosed; amycretin)

Comparatorsplacebo

Orforglipron MARKETED

weight-loss Decrease

High evidence

Once-daily oral non-peptide GLP-1RA (LY3502970, Lilly). In ATTAIN-1 phase 3 obesity (no T2D), 36 mg reduced body weight by 12.4% vs 0.9% placebo at 72 weeks. In...

Eli Lilly press + ATTAIN-1/ATTAIN-2 (NEJM; Lancet 2025), ACHIEVE-1 (NEJM 2025) Source

Full findingOnce-daily oral non-peptide GLP-1RA (LY3502970, Lilly). In ATTAIN-1 phase 3 obesity (no T2D), 36 mg reduced body weight by 12.4% vs 0.9% placebo at 72 weeks. In ATTAIN-2 (obesity + T2D), top dose gave 10.5% weight loss and HbA1c -1.8%. In ACHIEVE-1 (early T2D), HbA1c fell 1.2/1.5/1.5% (3/12/36 mg) vs 0.4% placebo with weight loss 4.5/5.8/7.6% vs 1.7% placebo.

PopulationATTAIN-1: obesity/overweight + comorbidity, 72 wk, placebo-controlled (3/12/36 mg). ATTAIN-2: obesity + T2D. ACHIEVE-1: T2D on diet/exercise

Fundingindustry - Eli Lilly (disclosed in publication)

Comparatorsplacebo

Pemvidutide INVESTIGATIONAL

weight-loss Decrease

Moderate evidence

In a 24-week MASLD trial, pemvidutide produced ~6% weight loss as a secondary outcome.

Pemvidutide in MASLD, 24-week, J Hepatol Rep 2025 Source

PopulationPeer-reviewed RCT / meta-analysis

FundingAltimmune

Petrelintide INVESTIGATIONAL

weight-loss Decrease

Very low evidence

Phase 1b: 6-week MAD gave ~5.3% and 5.1% weight loss at 0.6/1.2 mg weekly; 16-week MAD up to 8.6% mean vs 1.7% placebo, mild GI events. Phase 2b ZUPREME-1 (42 wk,...

Zealand Pharma phase 1b topline (GlobeNewswire June 2024); ZUPREME-1 phase 2b topline (Ze... Source

Full findingPhase 1b: 6-week MAD gave ~5.3% and 5.1% weight loss at 0.6/1.2 mg weekly; 16-week MAD up to 8.6% mean vs 1.7% placebo, mild GI events. Phase 2b ZUPREME-1 (42 wk, obesity/overweight without T2D) met its primary endpoint with up to 10.7% mean weight loss vs 1.7% placebo and 'placebo-like' GI tolerability.

Populationphase 1b MAD: healthy/overweight, 6 and 16 wk; ZUPREME-1: adults obesity/overweight without T2D, 42 wk

Fundingindustry - Zealand / Roche (trial sponsor; inferred from registration trial)

Comparatorsplacebo

Pramlintide DISCONTINUED

weight-loss Decrease

Very low evidence

Pramlintide, the first approved amylin analogue (US 2005), used as adjunct to insulin in type 1 and insulin-treated type 2 diabetes, produces modest HbA1c reductions...

Pramlintide (Symlin) approval and reviews; DrugBank DB01278; Vascular Health Risk Manag r... Source

Full findingPramlintide, the first approved amylin analogue (US 2005), used as adjunct to insulin in type 1 and insulin-treated type 2 diabetes, produces modest HbA1c reductions and weight loss (reported up to ~1.6 kg). Acts centrally (area postrema) to induce satiety, suppress prandial glucagon, slow gastric emptying and reduce prandial hyperglycaemia.

Populationadults with type 1 and insulin-treated type 2 diabetes (approved adjunct-to-insulin indication)

Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)

Comparatorsplacebo/insulin alone

Retatrutide INVESTIGATIONAL

weight-loss Decrease

Moderate evidence

Triple GIP/GLP-1/glucagon agonist (LY3437943, Eli Lilly). In phase 2 obesity, once-weekly s.c. retatrutide produced large dose-dependent weight loss; phase 3 TRIUMPH...

Jastreboff AM et al. (retatrutide phase 2), NEJM, 2023;389:514-526 Source

Full findingTriple GIP/GLP-1/glucagon agonist (LY3437943, Eli Lilly). In phase 2 obesity, once-weekly s.c. retatrutide produced large dose-dependent weight loss; phase 3 TRIUMPH subsequently reported weight loss up to ~29% at 68 weeks. Balanced agonist at GIPR, GLP-1R and GCGR, the glucagon arm proposed to add an energy-expenditure component atop incretin-driven appetite suppression.

PopulationPhase 2 NCT04881760: N=338 adults, BMI >=30 or 27-<30 with weight-related condition, 48 wk, placebo-controlled. TRIUMPH-4 NCT05931367: phase 3, 68 wk, obesity + knee OA. TRIUMPH-1: phase 3, 80 wk, obesity/overweight.

Fundingindustry-Eli Lilly

Comparatorsplacebo

Retatrutide INVESTIGATIONAL

weight-loss Decrease

High evidence

In retatrutide's first phase-3 trial, monotherapy produced 11.5-15.3% weight loss in type-2 diabetes; the glycaemic arm (HbA1c) is recorded separately...

Bajaj HS et al., Lancet, 2026 Source

Full findingIn retatrutide's first phase-3 trial, monotherapy produced 11.5-15.3% weight loss in type-2 diabetes; the glycaemic arm (HbA1c) is recorded separately (C2-RETATRUTIDE-GLY-02).

PopulationTRANSCEND-T2D-1 (NCT06354660): 537 adults with type-2 diabetes inadequately controlled by diet and exercise, retatrutide 4/9/12 mg vs placebo 1:1:1:1; 40-week phase-3 randomised double-blind placebo-controlled monotherapy RCT at 48 sites (USA/Mexico/India).

Fundingindustry-Eli Lilly

Retatrutide INVESTIGATIONAL

weight-loss Decrease

Very low evidence

Eli Lilly's TRIUMPH-1 phase 3 topline press release reported weight loss of up to 28.3% at 80 weeks with retatrutide 12 mg, with 45.3% of participants losing at least...

Eli Lilly, TRIUMPH-1 (retatrutide) Phase 3 topline press release, PRNewswire, 21 May 2026... Source

Full findingEli Lilly's TRIUMPH-1 phase 3 topline press release reported weight loss of up to 28.3% at 80 weeks with retatrutide 12 mg, with 45.3% of participants losing at least 30%; the high-BMI extension reported up to 30.3% at 104 weeks. These sponsor-announced results were not peer reviewed or posted as registry results at the catalogue date. The release reported no DXA, energy-expenditure or receptor-specific data, so it informs weight-loss efficacy rather than mechanism.

PopulationTRIUMPH-1 (NCT05929066): n=2,339, obesity without diabetes, 80 weeks +/- high-BMI extension to 104 weeks

Fundingindustry - Eli Lilly (trial sponsor; corporate topline announcement of its own TRIUMPH-1 trial)

Comparatorsplacebo

Semaglutide MARKETED

weight-loss Decrease

High evidence

The lower-dose (25 mg) registrational oral-semaglutide obesity trial gave ~14% weight loss.

Oral semaglutide 25 mg for obesity (OASIS-4), NEJM 2025 Source

PopulationOASIS-4 (NCT05564117): 307 adults without diabetes, BMI >=30 (or >=27 with an obesity-related complication), oral semaglutide 25 mg vs placebo 2:1; 71-week registrational randomised double-blind placebo-controlled RCT at 22 sites in four countries.

FundingNovo Nordisk

Semaglutide MARKETED

weight-loss Decrease

High evidence

Once-weekly subcutaneous semaglutide 2.4 mg produced a mean body-weight change of -14.9% vs -2.4% with placebo at week 68 (treatment-policy estimand; -17.3% vs -2.0%...

Wilding JPH et al., NEJM 2021 (STEP 1) Source

Full findingOnce-weekly subcutaneous semaglutide 2.4 mg produced a mean body-weight change of -14.9% vs -2.4% with placebo at week 68 (treatment-policy estimand; -17.3% vs -2.0% on the trial-product estimand); 86.4% reached >=5% weight loss vs 31.5% placebo.

PopulationSTEP 1: 1961 adults, BMI >=30 (or >=27 with comorbidity), without diabetes, 68 weeks, randomised double-blind vs placebo, adjunct to lifestyle

Fundingindustry - Novo Nordisk

Comparatorsplacebo

Semaglutide MARKETED

weight-loss Decrease

High evidence

Once-daily oral semaglutide 50 mg produced a mean body-weight change of -15.1% vs -2.4% placebo at week 68 (treatment-policy; -17.4% trial-product). In T2D (PIONEER...

Knop CR et al., Lancet 2023 (OASIS 1) Source

Full findingOnce-daily oral semaglutide 50 mg produced a mean body-weight change of -15.1% vs -2.4% placebo at week 68 (treatment-policy; -17.4% trial-product). In T2D (PIONEER PLUS) oral 50 mg gave ~2.0 percentage-point HbA1c reduction.

PopulationOASIS 1: adults with overweight/obesity without T2D, 9 countries, 68 weeks, randomised double-blind vs placebo; PIONEER PLUS: T2D, baseline HbA1c >=8%

Fundingindustry - Novo Nordisk (disclosed in publication)

Comparatorsplacebo

Setmelanotide MARKETED

weight-loss Decrease

Moderate evidence

In severe obesity from POMC or LEPR deficiency, ~1 year of setmelanotide produced significant weight loss and reduced hunger: >=10% weight loss in 80% (8/10) of...

Clement et al., Lancet Diabetes Endocrinol 2020 Source

Full findingIn severe obesity from POMC or LEPR deficiency, ~1 year of setmelanotide produced significant weight loss and reduced hunger: >=10% weight loss in 80% (8/10) of POMC-deficiency and 45% (5/11) of LEPR-deficiency participants. Marketed (Imcivree) for genetic MC4R-pathway obesity and Bardet-Biedl syndrome; positive in acquired hypothalamic obesity and ages 2-5 (VENTURE).

PopulationSingle-arm open-label multicentre phase 3, POMC and LEPR deficiency, participants aged >=6y; ~1-year endpoint

Fundingindustry - Rhythm Pharmaceuticals (setmelanotide; disclosed)

TERN-601 DISCONTINUED

weight-loss Decrease

Low evidence

Oral non-peptide GLP-1RA (Terns Pharmaceuticals). Phase 1 SAD/MAD in healthy adults with obesity/overweight reported dose-dependent placebo-adjusted weight loss up to...

Terns Pharmaceuticals press Sept 2024; ADA 85th Scientific Sessions June 2025 Source

Full findingOral non-peptide GLP-1RA (Terns Pharmaceuticals). Phase 1 SAD/MAD in healthy adults with obesity/overweight reported dose-dependent placebo-adjusted weight loss up to 4.9% at 740 mg once daily over 28 days; 67% lost >=5% at top dose; >95% TEAEs mild. Phase 2 FALCON ongoing (12-week primary endpoint).

PopulationPhase 1 randomised double-blind placebo-controlled SAD/MAD in healthy adults with obesity/overweight; phase 2 FALCON ongoing

Fundingindustry - Terns (trial sponsor; inferred from registration trial)

Comparatorsplacebo

Aleniglipron INVESTIGATIONAL

weight-loss Decrease

Moderate evidence

ACCESS phase 2b: met primary endpoint with dose-dependent placebo-adjusted weight loss at 36 weeks, no apparent plateau.

Rosenstock J et al. Oral small molecule GLP-1 receptor agonist aleniglipron in people wit... Source

PopulationACCESS phase 2b RCT (NCT06693843), N=230 adults with obesity/overweight (mean BMI 39.5, 54% female); 36 wk double-blind + OLE; once-daily escalated q4w; placebo comparator

Fundingindustry - Structure Therapeutics (via subsidiary Gasherbrum Bio, Inc.)

Comparatorsplacebo

Amycretin INVESTIGATIONAL

weight-loss Decrease

Low evidence

Subcutaneous amycretin produced large dose-dependent weight loss over 20-36 wk

Dahl K, Toubro S et al. Amycretin, unimolecular GLP-1 and amylin receptor agonist s.c.: p... Source

PopulationOverweight/obese (BMI 27-39.9), phase 1b/2a (n=125; 101 amycretin), up to 36 wk, RCT placebo-controlled (NCT06064006)

Fundingindustry - Novo Nordisk (trial sponsor; inferred from registration trial)

Comparatorsplacebo

Amycretin INVESTIGATIONAL

weight-loss Decrease

Moderate evidence

Oral amycretin: first-in-human pharmacodynamic weight reduction over 12 wk

Gasiorek A et al. Lancet 2025;406:135-148 Source

PopulationOverweight/obese (BMI 25-39.9), phase 1 first-in-human (n=144), single + multiple ascending oral doses (NCT05369390)

Fundingindustry - Novo Nordisk

Comparatorsplacebo

BI 3034701 INVESTIGATIONAL

weight-loss Not directional

Very low evidence

No human weight-loss data reported; rationale is multi-pathway satiety/body-weight regulation.

Boehringer Ingelheim / Gubra press disclosures, 2025-2026. Source

PopulationNone (preclinical/early clinical)

Fundingindustry (company press release on own pipeline)

Cagrilintide INVESTIGATIONAL

weight-loss Decrease

Moderate evidence

Dose-dependent weight loss; 4.5 mg superior to liraglutide 3.0 mg over 26 wk

Lau DCW et al. Lancet 2021;398:2160-2172 Source

PopulationAdults overweight/obese without diabetes (n=706 cagrilintide), phase 2 dose-finding, 26 wk, RCT double-blind placebo+active controlled (NCT03856047)

Fundingindustry - Novo Nordisk

Comparatorsplacebo; liraglutide 3.0 mg

CagriSema INVESTIGATIONAL

weight-loss Decrease

High evidence

REDEFINE 1: substantial weight loss vs placebo and vs each monocomponent in obesity without diabetes

Garvey WT, Blüher M, et al. N Engl J Med 2025 (REDEFINE 1) Source

PopulationAdults BMI ≥30 or ≥27+complication, no diabetes (n=3417; 2108 CagriSema), phase 3a, 68 wk, RCT placebo+active controlled (NCT05567796)

Fundingindustry-Novo Nordisk

Comparatorsplacebo; semaglutide 2.4 mg; cagrilintide 2.4 mg

CagriSema INVESTIGATIONAL

weight-loss Decrease

High evidence

REDEFINE 2: weight loss vs placebo in obesity WITH type 2 diabetes

Davies MJ, Bajaj HS, et al. N Engl J Med 2025 (REDEFINE 2) Source

PopulationAdults BMI ≥27, HbA1c 7-10%, T2D (n=1206; 904 CagriSema), phase 3a, 68 wk, RCT placebo-controlled (NCT05394519)

Fundingindustry-Novo Nordisk

Comparatorsplacebo

Cotadutide DISCONTINUED

weight-loss Decrease

Moderate evidence

Once-daily cotadutide reduced body weight vs placebo in overweight/obese T2D

Ambery P et al. Lancet 2018;391:2607-2618 Source

PopulationOverweight/obese T2D adults, phase 2a (n=51 randomised, 22 cotadutide analysed), 41 days, RCT, double-blind, placebo-controlled, up to 200 µg s.c.

Fundingindustry-AstraZeneca

Comparatorsplacebo

Cotadutide DISCONTINUED

weight-loss Decrease

Moderate evidence

54-week cotadutide reduced weight vs placebo; 200 µg similar to liraglutide 1.8 mg, 300 µg greater than liraglutide

Nahra R et al. Diabetes Care 2021;44:1433-1442 Source

PopulationOverweight/obesity + T2D on metformin (n=834), phase 2b, 54 wk, RCT double-blind, comparator open-label liraglutide 1.8 mg

Fundingindustry-AstraZeneca

Comparatorsplacebo; liraglutide 1.8 mg

Enicepatide INVESTIGATIONAL

weight-loss Decrease

Very low evidence

Phase 2 topline: clinically meaningful, statistically significant placebo-adjusted weight loss at the highest dose at 48 weeks.

Roche/Genentech press release: Roche announces positive Phase II results for dual GLP-1/G... Source

PopulationCT388-103, N=469 adults with obesity/overweight + >=1 comorbidity; 48 wk; phase 2 double-blind placebo-controlled RCT

Fundingindustry - Roche (trial sponsor; inferred from registration trial)

Comparatorsplacebo

Enicepatide INVESTIGATIONAL

weight-loss Decrease

Low evidence

Phase 1 (4 once-weekly doses) produced dose-dependent weight loss by day 29 in overweight/obese participants.

Chakravarthy MV et al. Effects of CT-388, a once-weekly signaling-biased dual GLP-1/GIP r... Source

PopulationPhase 1 double-blind RCT (NCT04838405), healthy participants with overweight/obesity; ~4 wk; placebo comparator

Fundingindustry - Roche

Comparatorsplacebo

Danuglipron DISCONTINUED

weight-loss Decrease

Moderate evidence

Phase 2b: statistically significant, dose-dependent weight reduction vs placebo over 26/32 weeks.

Buckeridge C et al. Efficacy and safety of danuglipron (PF-06882961) in adults with obesi... Source

PopulationPhase 2b RCT (NCT04707313), N=628 randomised (536 danuglipron, 90 placebo), adults with obesity without diabetes; danuglipron BID; placebo comparator

Fundingindustry - Pfizer

Comparatorsplacebo

Ecnoglutide MARKETED

weight-loss Decrease

Moderate evidence

Phase 3 (China): superior, sustained weight reduction vs placebo at 40 weeks in overweight/obese adults without diabetes.

Ji L et al. Efficacy and safety of a biased GLP-1 receptor agonist ecnoglutide in adults ... Source

PopulationPhase 3 RCT (NCT05813795), N=664, 36 Chinese centres, overweight/obese without diabetes; 40 wk; once-weekly SC; placebo comparator

Fundingindustry - Hangzhou Sciwind Biosciences (trial sponsor, disclosed in publication)

Comparatorsplacebo

Efinopegdutide INVESTIGATIONAL

weight-loss Decrease

Moderate evidence

Weight loss numerically greater than semaglutide but not statistically significant

Romero-Gómez M et al. A phase IIa active-comparator-controlled study to evaluate the effi... Source

PopulationNAFLD (n=145), phase 2a, 24 wk, open-label

Fundingindustry-Merck (Merck Sharp & Dohme LLC; efinopegdutide licensed from Hanmi)

Comparatorssemaglutide 1 mg

Lotiglipron DISCONTINUED

weight-loss Not directional

Very low evidence

Weight-loss/glycaemic efficacy was being evaluated in mid-stage trials but development halted before mature efficacy data were published.

Pfizer press / CNBC: Pfizer to end development of experimental obesity pill lotiglipron, ... Source

PopulationPhase 1/2 (obesity, T2D); halted 2023

Fundingindustry - Pfizer (trial sponsor; inferred from registration trial)

LY3537021 INVESTIGATIONAL

weight-loss Decrease

Low evidence

Selective GIPR agonist monotherapy induced dose-dependent body-weight reduction in a phase 1 MAD study, persisting after last dose.

Long-acting GIPR agonist LY3537021 reduces body weight and fasting glucose in T2D: precli... Source

PopulationPhase 1 SAD/MAD RCT (NCT04586907), Singapore; N=85 (SAD n=47, MAD n=38) healthy + T2D; baseline BMI 25.9-27.0; placebo comparator

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Comparatorsplacebo

MariTide INVESTIGATIONAL

weight-loss Decrease

Moderate evidence

Once-monthly subcutaneous maridebart cafraglutide produced substantial weight reduction without an apparent plateau at 52 weeks in adults with obesity (no diabetes);...

Jastreboff AM et al. Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - ... Source

Full findingOnce-monthly subcutaneous maridebart cafraglutide produced substantial weight reduction without an apparent plateau at 52 weeks in adults with obesity (no diabetes); dose-ranging.

PopulationObesity cohort, N=465 (63% female; mean age 47.9 y; mean BMI 37.9); 52 wk; phase 2 double-blind RCT; comparator placebo

Fundingindustry - Amgen

Comparatorsplacebo

MariTide INVESTIGATIONAL

weight-loss Decrease

Moderate evidence

Weight reduction in the obesity-with-type-2-diabetes cohort, lower in magnitude than the non-diabetes cohort.

Jastreboff AM et al. Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - ... Source

PopulationObesity + T2D cohort, N=127 (42% female; mean age 55.1 y; mean BMI 36.5); 52 wk; phase 2 RCT; placebo comparator

Fundingindustry - Amgen

Comparatorsplacebo

Mazdutide MARKETED

weight-loss Decrease

Low evidence

High-dose mazdutide produced marked early weight loss vs placebo in Chinese overweight/obese adults

Ji L et al. EClinicalMedicine 2022;54:101691 Source

PopulationChinese overweight/obese adults (n=24), phase 1b MAD, 12-16 wk, RCT placebo-controlled (NCT04440345)

Fundingindustry - Innovent / Eli Lilly (trial sponsor; inferred from registration trial)

Comparatorsplacebo

Mazdutide MARKETED

weight-loss Decrease

Moderate evidence

Phase 3 GLORY-1 confirmed substantial weight loss vs placebo at 48 wk

Mazdutide in Chinese adults with obesity (GLORY-1), NEJM 2025 Source

PopulationChinese overweight/obese with ≥1 comorbidity (n=610), phase 3, 48 wk, RCT (4/6 mg vs placebo); NEJM 10.1056/NEJMoa2411528

FundingInnovent Biologics

Comparatorsplacebo

Orforglipron MARKETED

weight-loss Decrease

High evidence

ATTAIN-1 (obesity, no diabetes): superior body-weight reduction vs placebo at all three doses at 72 weeks.

Lilly ATTAIN-1 (NEJM 2025) and ATTAIN-2 results Source

PopulationATTAIN-1, adults with obesity (or overweight + comorbidity) without diabetes; 72 wk; phase 3 double-blind placebo-controlled RCT (NCT05869903); doses 6/12/36 mg vs placebo

Fundingindustry - Eli Lilly

Comparatorsplacebo

Orforglipron MARKETED

weight-loss Decrease

High evidence

ATTAIN-2 (obesity + T2D): dose-dependent weight reduction superior to placebo at 72 weeks.

Horn DB et al. Orforglipron... for obesity in people with type 2 diabetes (ATTAIN-2): a p... Source

PopulationATTAIN-2, N=1613 (47% female; mean baseline weight 101.4 kg, BMI 35.6, HbA1c 8.05%); 72 wk; phase 3 RCT (NCT05872620); 6/12/36 mg vs placebo

Fundingindustry-Eli Lilly

Comparatorsplacebo

Orforglipron MARKETED

weight-loss Decrease

High evidence

ACHIEVE-1 secondary: body-weight reduction at 40 weeks in early T2D.

Rosenstock J, Hsia S, et al. N Engl J Med 2025 (ACHIEVE-1) Source

PopulationACHIEVE-1, N=559; 40 wk; phase 3 RCT (NCT05971940)

Fundingindustry-Eli Lilly

Comparatorsplacebo

Pemvidutide INVESTIGATIONAL

weight-loss Decrease

Very low evidence

Dose-dependent weight loss over 48 wk in obesity/overweight without diabetes (MOMENTUM)

Altimmune MOMENTUM topline / ADA 2024 Source

PopulationObese/overweight + ≥1 comorbidity, no diabetes (n=391), phase 2 MOMENTUM, 48 wk, RCT 1:1:1:1

Fundingindustry - Altimmune (trial sponsor; inferred from registration trial)

Comparatorsplacebo

Petrelintide INVESTIGATIONAL

weight-loss Decrease

Very low evidence

Phase 1b MAD: dose-dependent weight loss over 16 weekly doses

Zealand Pharma topline press release, 20 Jun 2024 Source

PopulationOverweight/obese, median BMI 29, median age 49 (n=48), phase 1b MAD, 16 wk, RCT placebo-controlled

Fundingindustry - Zealand / Roche (trial sponsor; inferred from registration trial)

Comparatorsplacebo

Pramlintide DISCONTINUED

weight-loss Decrease

High evidence

Modest weight loss vs weight gain on insulin alone

Hollander PA, Levy P, Fineman MS, et al. 'Pramlintide as an adjunct to insulin therapy im... Source

PopulationT2D on mealtime insulin, FDA registration trials

Fundingindustry - Amylin Pharmaceuticals (pramlintide developer)

Comparatorsplacebo + insulin

Survodutide INVESTIGATIONAL

weight-loss Decrease

Moderate evidence

Dose-dependent weight loss vs placebo over 46 weeks in obesity without diabetes

le Roux CW et al. Lancet Diabetes Endocrinol 2024;12:162-173 Source

PopulationAdults BMI ≥27 without diabetes (n=387), phase 2 dose-finding, 46 wk, RCT double-blind, placebo-controlled (NCT04667377)

Fundingindustry-Boehringer Ingelheim

Comparatorsplacebo

TERN-601 DISCONTINUED

weight-loss Decrease

Very low evidence

FALCON phase 2 (12-week topline): modest placebo-adjusted weight loss; program subsequently discontinued.

Terns Pharmaceuticals press release: Topline 12-week data from Phase 2 trial of oral GLP-... Source

PopulationFALCON phase 2 RCT, US multicentre, adults with obesity/overweight without diabetes; n=30 per active cohort + placebo; 12-wk topline

Fundingindustry - Terns

Comparatorsplacebo

Most represented records

Evidence spread