Obesity Pharmacotherapy — Approved & Phase 2/3 Pipeline
Approved anti-obesity medications (AOM) and the investigational Phase 2/3 pipeline, grouped by drug. Use the category switch (All · Phase 2 · Phase 3 · Approved). Educational resource — nephrobesity.
Data verified against ClinicalTrials.gov and primary publications · last comprehensively reviewed August 2026
Educational use only. This view mixes approved anti-obesity drugs and investigational Phase 2/3 agents — each card states its regulatory status (see the category switch and status badges). Cross-trial weight-loss figures are not head-to-head and differ in duration, estimand, dose, and population — compare with care. Verify against the primary source before applying to care.
Mechanism of action & kidney effects — pharmacology overview▸
Receptor targets → physiological effects
The incretin-based agents act through different combinations of receptors. This simplified, qualitative map shows which receptor axis drives each effect — it is a teaching schematic, not a quantitative comparison. GIP’s contribution to weight loss is mechanism-debated (both agonism and antagonism are in clinical development).
GLP-1GIPGIP antag.GlucagonAmylinMC4RActivin
| Effect | GLP-1 | GIP | GIP antag. | Glucagon | Amylin | MC4R | ActRII |
|---|---|---|---|---|---|---|---|
| ↓ Appetite / ↑ satiety central (hypothalamic / hindbrain) | – | – | |||||
| ↓ Gastric emptying slowed gastric transit | – | – | – | – | – | ||
| ↑ Insulin (glucose-dependent) & ↓ glucagon secretion | – | – | – | – | |||
| ↑ Energy expenditure & ↓ hepatic fat (MASH) | – | – | – | – | |||
| Kidney: ↓ hyperfiltration, ↓ UACR natriuresis, anti-inflammatory | – | – | – | – | – | ||
| Cardiovascular: ↓ MACE / HF risk weight, BP, inflammation | – | – | – | ||||
| Lean-mass preservation ↑ lean, ↓ fat — muscle-preserving (ActRII blockade) | – | – | – | – | – | – |
direct / primary effectcontributory / indirect– not a principal effect
Drug classes by receptor combination
Each class combines the receptor axes above; the colour chips show which receptors the agents engage.
GLP-1
GLP-1 receptor agonist
Satiety, slowed gastric emptying, glucose-dependent insulin; the best-evidenced renal/CV class.
Semaglutide, liraglutide, orforglipron
GLP-1GIP
GLP-1 / GIP dual agonist
Adds GIP-receptor agonism to the GLP-1 axis; large weight-loss magnitude.
Tirzepatide
GLP-1Glucagon
GLP-1 / glucagon dual
Glucagon agonism raises energy expenditure and lowers hepatic fat; GLP-1 offsets glucose rise.
Survodutide, mazdutide, pemvidutide
GIP antag.GLP-1
GIP antagonist + GLP-1 agonist
GLP-1 agonism combined with GIP-receptor antagonism (opposite GIP direction).
Maridebart cafraglutide (MariTide)
GLP-1GIPGlucagon
GLP-1 / GIP / glucagon tri-agonist
Engages all three incretin/glucagon axes; among the largest weight-loss signals.
Retatrutide
Amylin(± GLP-1)
Amylin analogue (± GLP-1)
Amylin agonism complements GLP-1 (satiety, gastric emptying, glucagon).
Petrelintide; CagriSema (cagrilintide + semaglutide)
MC4R
Melanocortin-4 receptor agonist
Central appetite regulation downstream of leptin–POMC; used in monogenic obesity.
Setmelanotide
ActRII
Activin receptor (muscle-preserving)
Blocks activin type-II signalling to increase lean mass while reducing fat mass.
Bimagrumab (often combined with semaglutide)
Non-incretin
Older / established agents
Reward/appetite (opioid–dopamine), sympathomimetic + GABA/glutamate, or intestinal lipase inhibition.
Naltrexone–bupropion, phentermine–topiramate, orlistat, phentermine
eGFR trajectory under incretin therapy
Renoprotective agents characteristically show a small early haemodynamic change followed by an attenuated long-term eGFR decline versus control. The curve on the left is a schematic of that pattern; the panel on the right lists the actual, source-verified slope data.
Schematic — illustrative pattern, not raw trial data. Absolute eGFR values are generic. The clinically meaningful quantity is the between-group slope difference, shown with verified numbers at right.
FLOW — semaglutide 1.0 mg vs placebo
- Total eGFR slope 1.16 mL/min/1.73m²/yr less steep vs placebo (p<0.001)
- Primary kidney composite HR 0.76 (95% CI 0.66–0.88; p=0.0003)
SURPASS-4 — tirzepatide vs insulin glargine
- Annual eGFR slope −1.4 vs −3.6 (Δ 2.2, 95% CI 1.6–2.8) mL/min/1.73m²/yr
- UACR between-group −31.9%; kidney composite HR 0.58 (0.43–0.80)
Interpretation. The clearest acute haemodynamic eGFR dip is seen with SGLT2 inhibitors; GLP-1 receptor agonists appear to protect the kidney mainly via reduced glomerular hyperfiltration, natriuresis and anti-inflammatory effects. Trials differ in comparator, population and analysis (FLOW is placebo-controlled; SURPASS-4 renal data are post-hoc vs insulin glargine) — figures are not head-to-head.
Methodology, inclusion criteria & data currency — how this list is built▸
Data sources Every entry is checked against its ClinicalTrials.gov record (NCT, phase, status, enrolment, population, comparator, primary endpoint, dates) and, where results exist, against the primary publication or the sponsor’s topline release. Journal links in the “Result” column point to the primary result paper on PubMed.
Last comprehensively reviewed August 2026. Figures not yet in the public record are marked results pending / readout expected rather than estimated.
Included Approved anti-obesity medications and investigational agents in Phase 2 or Phase 3 development for obesity / weight management, plus their cardiorenal and comorbidity sub-studies. The scope toggle switches between Pivotal (the key weight-management and cardiorenal/outcome trials) and Full programme (adds comorbidity sub-studies: OSA, osteoarthritis, hypertension, PAD, heart failure, MASH/liver, CKD, adolescents).
Excluded Pure glycaemic / type-2-diabetes-only trials and non-obesity indications (e.g., myositis, sarcopenia, COPD).
Renal & CV markers The renal marker is derived from each trial’s actual ClinicalTrials.gov outcome measures (eGFR/mGFR, UACR/albuminuria, creatinine, ESKD, nephropathy): 1° = renal primary endpoint, 2° = renal secondary. Use “Renal endpoint only” to list the agents with dedicated CKD / renal-outcome data. “Cardiovascular” marks a CV / heart-failure / PAD population or a MACE / HF primary endpoint.
Population note: Weight-loss efficacy is consistently lower in people with type 2 diabetes (semaglutide −14.9% in STEP 1 without T2D vs −9.6% in STEP 2 with T2D; tirzepatide −20.9% in SURMOUNT-1 vs −14.7% in SURMOUNT-2). Headline figures below preferentially reflect obesity trials without diabetes where available.
Mechanism
Phase
Status
RetatrutideLY3437943
InvestigationalFDA filing planned 2027 (quarter unconfirmed)
−28.3%
−28.3% · Ph3 TRIUMPH-1 topline (May 2026) · not yet peer-reviewed · 12 mg, wk 80
How the trials differ: Programme splits by population: -1 no diabetes · -2 with T2D · -3 severe obesity + established CVD · -4 knee osteoarthritis · -5 head-to-head vs tirzepatide · -6 weight maintenance · -Outcomes CV & kidney events · TRANSCEND-CKD renal function (mGFR).
| Trial | Phase | N | Population | Comparator | Primary endpoint | Result / readout | Status | Source |
|---|---|---|---|---|---|---|---|---|
| Phase 2 dose-finding, no T2D |
Ph 2 | 338 | Obesity, no diabetes | Placebo | % body weight, wk 24 (primary) | −17.5% (12 mg) at wk 24 (primary); −24.2% at wk 48 (NEJM 2023) | Completed | NCT04881760↗ |
| TRIUMPH-1 no T2D |
Ph 3 | 2,335 | Obesity/overweight, no T2D | Placebo | % body weight, wk 80 | −28.3% (12 mg) vs −2.2% (topline May 2026) | Completed | NCT05929066↗ |
| TRIUMPH-2 with T2D |
Ph 3 | 1,152 | Obesity + type 2 diabetes | Placebo | % body weight, wk 80 | −20.8% (12 mg) vs −4.0%; HbA1c −1.5 pp (12 mg), up to −1.6 pp (9 mg) (Jul 2026) | Completed | NCT05929079↗ |
| TRIUMPH-3 Cardiovascular established CVD |
Ph 3 | 1,946 | Severe obesity + established CVD | Placebo | % body weight, wk 80 | −22.6% (12 mg) vs −3.2%; MACE-5 HR 0.82 (0.55–1.22), not powered | Completed | NCT05882045↗ |
| TRIUMPH-4 knee osteoarthritis |
Ph 3 | 445 | Obesity + knee OA | Placebo | WOMAC pain + % body weight, wk 68 | Results pending | Completed | NCT05931367↗ |
| TRIUMPH-5 head-to-head |
Ph 3 | 800 | Obesity | Tirzepatide (active) | % body weight, wk 80 | Readout expected late 2026 | Active, not recruiting | NCT06662383↗ |
| TRIUMPH-6 weight maintenance |
Ph 3 | 643 | Obesity (maintenance after lead-in) | Placebo (randomized withdrawal) | % body weight, wk 116 | Maintenance/withdrawal trial; ~2028 | Active, not recruiting | NCT06859268↗ |
| TRIUMPH-Outcomes Renal 1° Cardiovascular CV & kidney outcomes Renal endpoint: kidney composite (ESKD, ≥40% eGFR decline) |
Ph 3 | 10,000 | BMI ≥27 + ASCVD and/or CKD | Placebo (event-driven) | MACE + renal composite | Event-driven; ~2029 | Active, not recruiting | NCT06383390↗ |
| TRANSCEND-CKD Renal 1° CKD · mGFR Renal endpoint: mGFR (iohexol clearance) |
Ph 2 | 146 | Overweight/obese + CKD | Placebo | Measured GFR (iohexol), wk 24 | Completed Oct 2025; results pending (design/baseline: NDT 2026) | Completed | NCT05936151↗ |
OrforglipronLY3502970 · Foundayo
ApprovedFDA-approved for weight management, Apr 2026
−12.4%
−12.4% · Ph3 ATTAIN-1, 36 mg oral, wk 72
How the trials differ: First oral small-molecule GLP-1 for weight. ATTAIN-1 no T2D · ATTAIN-2 with T2D · ATTAIN-J Japan · Maintenance after injectable GLP-1 · CVOT CV/kidney outcomes.
| Trial | Phase | N | Population | Comparator | Primary endpoint | Result / readout | Status | Source |
|---|---|---|---|---|---|---|---|---|
| Phase 2 dose-finding |
Ph 2 | 272 | Obesity, no diabetes | Placebo | % body weight, wk 26 | ~−14.7% at wk 36 (NEJM 2023) | Completed | NCT05051579↗ |
| ATTAIN-1 no T2D |
Ph 3 | 3,127 | Obesity/overweight, no T2D | Placebo | % body weight, wk 72 | −12.4% (36 mg) vs −0.9% (NEJM 2025) | Active, not recruiting | NCT05869903↗ |
| ATTAIN-2 with T2D |
Ph 3 | 1,613 | Obesity + type 2 diabetes | Placebo | % body weight, wk 72 | −10.5% vs −2.2%; HbA1c −1.8 pp (Lancet 2026) | Completed | NCT05872620↗ |
| ATTAIN-J Japan |
Ph 3 | 238 | Japanese adults with obesity | Placebo | % body weight + ≥5% responders, wk 72 | Completed Jun 2025; results pending | Completed | NCT05931380↗ |
| ATTAIN-Maintenance maintenance |
Ph 3 | 376 | After injectable tirzepatide/semaglutide | Placebo | Weight maintenance, wk 52 | Results pending | Completed | NCT06584916↗ |
| CVOT Renal 2° Cardiovascular CV & kidney outcomes Renal endpoint: CV+kidney composite; eGFR slope |
Ph 3 | 7,140 | Established ASCVD and/or CKD | Placebo (event-driven) | MACE composite | Started Dec 2025; ~2031 | Recruiting | NCT07241390↗ |
CagriSemacagrilintide + semaglutide
Filed — under FDA reviewFDA review since Dec 2025
−20.4%
−20.4% · Ph3 REDEFINE-1, wk 68 (treatment-policy)
How the trials differ: Fixed-dose amylin + GLP-1. REDEFINE-1 no T2D · REDEFINE-2 with T2D · REDEFINE-3 CV outcomes · REDEFINE-4 head-to-head vs tirzepatide.
| Trial | Phase | N | Population | Comparator | Primary endpoint | Result / readout | Status | Source |
|---|---|---|---|---|---|---|---|---|
| REDEFINE-1 no T2D |
Ph 3 | 3,400 | Obesity, no T2D | Placebo (+ mono arms) | % body weight, wk 68 | −20.4% (treatment-policy) / −22.7% on-treatment (NEJM 2025) | Active, not recruiting | NCT05567796↗ |
| REDEFINE-2 with T2D |
Ph 3 | 1,200 | Obesity + type 2 diabetes | Placebo | % body weight, wk 68 | −15.7% (trial-product) / −13.7% (treatment-policy) vs placebo (topline) | Completed | NCT05394519↗ |
| REDEFINE-3 Renal 2° Cardiovascular established CVD Renal endpoint: eGFR / albuminuria composite |
Ph 3 | 7,101 | Obesity + established CVD | Placebo (event-driven) | 3-point MACE | CV outcomes; readout ~2027 | Active, not recruiting | NCT05669755↗ |
| REDEFINE-4 head-to-head vs tirzepatide |
Ph 3 | 809 | Obesity | Tirzepatide 15 mg | % body weight, wk 84 (non-inferiority) | ≈−23%; did not meet non-inferiority vs tirzepatide (2026) | Completed | NCT06131437↗ |
SurvodutideBI 456906
InvestigationalInvestigational
−13%
−13.0% · Ph3 SYNCHRONIZE-1, 6 mg, wk 76
How the trials differ: GLP-1/glucagon dual (also a strong MASH programme, not shown). SYNCHRONIZE-1 no T2D · -2 with T2D · -CVOT CV outcomes in CVD/CKD.
| Trial | Phase | N | Population | Comparator | Primary endpoint | Result / readout | Status | Source |
|---|---|---|---|---|---|---|---|---|
| Phase 2 dose-finding |
Ph 2 | 387 | Obesity, no diabetes | Placebo | % body weight, wk 46 | −14.9% (4.8 mg, MMRM) at wk 46 | Completed | NCT04667377↗ |
| SYNCHRONIZE-1 no T2D |
Ph 3 | 726 | Obesity, no T2D | Placebo | % body weight, wk 76 | −13.0% (6 mg) vs −5.4% (NEJM Jun 2026) | Completed | NCT06066515↗ |
| SYNCHRONIZE-2 with T2D |
Ph 3 | 755 | Obesity + type 2 diabetes | Placebo | % body weight, wk 76 | Results pending | Completed | NCT06066528↗ |
| SYNCHRONIZE-CVOT Cardiovascular CVD/CKD outcomes |
Ph 3 | 5,531 | Overweight/obese + CVD and/or CKD | Placebo (event-driven) | MACE-plus (CV safety) | Completed Jun 2026; results pending | Completed | NCT06077864↗ |
Maridebart cafraglutideAMG 133 · MariTide
InvestigationalInvestigational · once-monthly
−19.9%
−19.9% · Ph2, no T2D, wk 52 (efficacy)
How the trials differ: GIP-antagonist + GLP-1, monthly dosing. MARITIME-1 no T2D · -2 with T2D · -CV CV outcomes · -HF heart failure (HFpEF/HFmrEF) + obesity.
| Trial | Phase | N | Population | Comparator | Primary endpoint | Result / readout | Status | Source |
|---|---|---|---|---|---|---|---|---|
| Phase 2 ± T2D |
Ph 2 | 592 | Obesity ± type 2 diabetes | Placebo | % body weight, wk 52 | −19.9% (no T2D) / −17.0% (T2D), efficacy estimand (NEJM 2025;393:843) | Completed | NCT05669599↗ |
| MARITIME-1 no T2D |
Ph 3 | 3,853 | Obesity/overweight, no T2D | Placebo | % body weight, wk 72 | Readout ~2026–27 | Active, not recruiting | NCT06858839↗ |
| MARITIME-2 Renal 2° with T2D Renal endpoint: UACR |
Ph 3 | 1,105 | Obesity + type 2 diabetes | Placebo | % body weight, wk 72 | Results pending | Active, not recruiting | NCT06858878↗ |
| MARITIME-CV Renal 2° Cardiovascular CV outcomes Renal endpoint: UACR; eGFR slope; nephropathy composite |
Ph 3 | 12,800 | Established ASCVD + overweight/obese | Placebo (event-driven) | MACE; renal/BP secondary | Event-driven CV outcomes | Recruiting | NCT07037433↗ |
| MARITIME-HF Renal 2° Cardiovascular heart failure Renal endpoint: nephropathy composite; eGFR slope; UACR |
Ph 3 | 5,056 | HFpEF/HFmrEF + obesity | Placebo (event-driven) | HF composite (HHF/urgent visit/CV death) | ~2030 | Recruiting | NCT07037459↗ |
VK2735VK2735
InvestigationalInvestigational · SC and oral
−14.7%
−14.7% · Ph2 VENTURE (SC), wk 13 (short)
How the trials differ: GLP-1/GIP dual in both injectable and oral forms. VENTURE = Ph2 (SC & oral, 13 wk) · VANQUISH-1/2 = pivotal Ph3 (78 wk), no-T2D and T2D.
| Trial | Phase | N | Population | Comparator | Primary endpoint | Result / readout | Status | Source |
|---|---|---|---|---|---|---|---|---|
| VENTURE (SC) Ph2 · 13 wk |
Ph 2 | 176 | Obesity, no diabetes | Placebo | % body weight, wk 13 | −14.7% (15 mg) vs −1.7% at wk 13 | Completed | NCT06068946↗ |
| VENTURE-Oral oral · 13 wk |
Ph 2 | 280 | Obesity | Placebo | % body weight, wk 13 | −12.2% (oral) vs −1.3% at wk 13 | Completed | NCT06828055↗ |
| VANQUISH-1 no T2D · pivotal |
Ph 3 | 4,500 | Obesity, no T2D | Placebo | % body weight, wk 78 | Readout ~2027 | Active, not recruiting | NCT07104500↗ |
| VANQUISH-2 with T2D |
Ph 3 | 1,100 | Type 2 diabetes, BMI ≥27 | Placebo | % body weight, wk 78 | Readout ~2027 | Active, not recruiting | NCT07104383↗ |
PemvidutideALT-801
InvestigationalInvestigational
−15.6%
−15.6% · Ph2 MOMENTUM, 2.4 mg, wk 48
How the trials differ: GLP-1/glucagon dual with notably high lean-mass preservation. MOMENTUM = Ph2 obesity; VELOCITY = planned Ph3 series (not yet registered).
| Trial | Phase | N | Population | Comparator | Primary endpoint | Result / readout | Status | Source |
|---|---|---|---|---|---|---|---|---|
| MOMENTUM lean-mass sparing |
Ph 2 | 391 | Obesity, no diabetes | Placebo | % body weight, wk 48 | −15.6% (2.4 mg) vs −2.2%; ~21% of loss lean mass | Completed | NCT05295875↗ |
| VELOCITY (planned) Ph3 · not yet registered |
Ph 3 | 5,000 | Obesity (4-trial series) | Placebo | % body weight, ~wk 60 | FDA-aligned Nov 2024; no NCT yet | Planned | — |
PetrelintideZP8396
InvestigationalInvestigational
−10.7%
−10.7% · Ph2 ZUPREME-1, wk 42 (primary wk 28)
How the trials differ: Long-acting amylin analogue (potential GLP-1-sparing profile). ZUPREME-1 no T2D · ZUPREME-2 with T2D · ZYNERGY combo with a GLP-1/GIP agonist (enicepatide).
| Trial | Phase | N | Population | Comparator | Primary endpoint | Result / readout | Status | Source |
|---|---|---|---|---|---|---|---|---|
| ZUPREME-1 no T2D |
Ph 2 | 493 | Obesity, no diabetes | Placebo | % body weight, wk 28 (primary) | −10.7% (top dose) vs −1.7% at wk 42 (topline Mar 2026) | Completed | NCT06662539↗ |
| ZUPREME-2 with T2D |
Ph 2 | 221 | Obesity + type 2 diabetes | Placebo | % body weight, wk 28 | Readout H2 2026 | Active, not recruiting | NCT06926842↗ |
| ZYNERGY combo |
Ph 2 | 486 | Obesity | Placebo, mono, + enicepatide combo | % body weight, wk 40 | Starts ~2026 | Not yet recruiting | NCT07589686↗ |
MazdutideIBI362 / LY3305677
ApprovedApproved in China (Jun 2025); investigational elsewhere
−18.6%
−18.6% · Ph3 GLORY-2, 9 mg, wk 60
How the trials differ: GLP-1/glucagon dual, developed mainly in China (GLORY programme). GLORY-1 registration · GLORY-2 higher dose, severe obesity · plus a Phase 3 in MAFLD vs semaglutide (no registry acronym).
| Trial | Phase | N | Population | Comparator | Primary endpoint | Result / readout | Status | Source |
|---|---|---|---|---|---|---|---|---|
| Phase 2 dose-finding (China) |
Ph 2 | 328 | Overweight/obese (China) | Placebo | % body weight, wk 24 | −11.3% (6 mg) vs +1.0% (Nat Commun 2023) | Completed | NCT04904913↗ |
| GLORY-1 registration |
Ph 3 | 610 | Overweight/obese (China) | Placebo | % body weight, wk 32 (primary) | −13.38% (6 mg) at wk 32 (primary); −14.84% at wk 48 (NEJM 2025) | Completed | NCT05607680↗ |
| GLORY-2 9 mg · severe obesity |
Ph 3 | 462 | Moderate–severe obesity (BMI ≥30) | Placebo | % body weight, wk 60 | −18.55% (9 mg) vs −3.02%; −20.1% in non-diabetes subgroup (JAMA 2026) | Active, not recruiting | NCT06164873↗ |
| Ph3 vs semaglutide + MAFLD · head-to-head |
Ph 3 | 479 | Overweight/obese + MAFLD | Semaglutide 2.4 mg | MRI-PDFF liver fat + % body weight, wk 48 | Ongoing (registry lists no GLORY-3 acronym) | Active, not recruiting | NCT06884293↗ |
BimagrumabBYM338
InvestigationalInvestigational · distinct mechanism
−16.4%
−16.4% · Ph2 BELIEVE, combo w/ semaglutide, wk 48 (treatment-regimen)
How the trials differ: Activin-receptor antibody — loses fat while preserving/increasing lean mass; studied mainly in combination. BELIEVE w/ semaglutide · Ph2b w/ tirzepatide.
| Trial | Phase | N | Population | Comparator | Primary endpoint | Result / readout | Status | Source |
|---|---|---|---|---|---|---|---|---|
| BELIEVE + semaglutide |
Ph 2 | 507 | Overweight/obese | Placebo, semaglutide, combos | body weight, wk 48 | Combo w/ semaglutide −16.4% (−17.8 kg); bimagrumab alone −8.6%; preserves lean mass (−2.3% vs −6.9% for semaglutide alone) (Nat Med 2026) | Completed | NCT05616013↗ |
| Phase 2b + tirzepatide, no T2D |
Ph 2 | 252 | Obesity, no T2D | Placebo, tirzepatide, combos | % body weight, wk 24 | Readout 2026 | Active, not recruiting | NCT06643728↗ |
| Proof-of-concept T2D · fat mass |
Ph 2 | 78 | Obese + type 2 diabetes | Placebo | Total fat mass (DXA), wk 48 | Fat −7.5 kg vs −0.2 kg; lean-mass gain (JAMA Netw Open 2021) | Completed | NCT03005288↗ |
SemaglutideWegovy · Ozempic
ApprovedFDA-approved 2021 (Wegovy 2.4 mg)
−14.9%
−14.9% · STEP 1, 2.4 mg, wk 68
How the trials differ: GLP-1 receptor agonist. STEP = weight programme (1 no T2D, 2 T2D, 3 behavioral, 4 maintenance, 5 two-year, 8 vs liraglutide, OASIS oral) · SELECT CV outcomes · FLOW kidney outcomes · STEP-HFpEF · ESSENCE MASH.
| Trial | Phase | N | Population | Comparator | Primary endpoint | Result / readout | Status | Source |
|---|---|---|---|---|---|---|---|---|
| STEP 1 no T2D |
Ph 3 | 1,961 | Metabolism and Nutrition Disorder, Overwei… | Placebo / vs semaglutide | Change in Body Weight (%) wk 68 | −14.9% vs −2.4% (NEJM 2021) | Completed | NCT03548935↗ |
| STEP 2 with T2D |
Ph 3 | 1,210 | Obesity, Overweight | Placebo / vs semaglutide | Change in Body Weight (%) – Semaglutide … wk 68 | −9.6% vs −3.4% (Lancet 2021) | Completed | NCT03552757↗ |
| SELECT Renal 2° Cardiovascular CV outcomes Renal endpoint: nephropathy composite |
Ph 3 | 17,604 | Overweight, Obesity | Placebo / vs semaglutide | Participants From Time of Randomization … wk 0 | MACE −20%, HR 0.80 (0.72–0.90) (NEJM 2023); kidney composite HR 0.78 | Completed | NCT03574597↗ |
| FLOW Renal 1° Cardiovascular CKD outcomes · 1.0 mg Renal endpoint: eGFR · ESKD/RRT · renal death |
Ph 3 | 3,533 | Diabetes Mellitus, Type 2 | Placebo / vs semaglutide | Number of Participants From Time of Rand… wk 234 | kidney composite −24%, HR 0.76 (0.66–0.88) (NEJM 2024) | Completed | NCT03819153↗ |
TirzepatideZepbound · Mounjaro
ApprovedFDA-approved 2023 (Zepbound)
−20.9%
−20.9% · SURMOUNT-1, 15 mg, wk 72 (treatment-regimen)
How the trials differ: GLP-1/GIP dual agonist. SURMOUNT = weight programme (1 no T2D, 2 T2D, 3 lifestyle, 4 maintenance, 5 vs semaglutide, MMO outcomes, OSA) · SUMMIT HFpEF · TREASURE-CKD renal.
| Trial | Phase | N | Population | Comparator | Primary endpoint | Result / readout | Status | Source |
|---|---|---|---|---|---|---|---|---|
| SURMOUNT-1 no T2D |
Ph 3 | 2,539 | Overweight, Obesity | Placebo / vs tirzepatide | Percent Change From Baseline in Body Wei… wk 72 | −20.9% (15 mg) vs −3.1% (NEJM 2022) | Completed | NCT04184622↗ |
| SURMOUNT-2 with T2D |
Ph 3 | 938 | Type 2 Diabetes, Overweight, Obesity | Placebo / vs tirzepatide | Percent Change From Baseline in Body Wei… wk 72 | −14.7% (15 mg) vs −3.2% (Lancet 2023) | Completed | NCT04657003↗ |
LiraglutideSaxenda
ApprovedApproved 2014 (Saxenda 3.0 mg)
−8%
−8.0% · SCALE, 3.0 mg, wk 56
How the trials differ: GLP-1 receptor agonist (daily). SCALE programme: obesity/prediabetes, diabetes, weight maintenance.
| Trial | Phase | N | Population | Comparator | Primary endpoint | Result / readout | Status | Source |
|---|---|---|---|---|---|---|---|---|
| SCALE Ob/Prediab no T2D |
Ph 3 | 3,731 | Metabolism and Nutrition Disorder, Obesity | Placebo / vs liraglutide | Change From Baseline in Fasting Body Wei… wk 56 | −8.0% vs −2.6% (NEJM 2015) | Completed | NCT01272219↗ |
Naltrexone–BupropionContrave · Mysimba
ApprovedApproved 2014 (Contrave/Mysimba)
−6.1%
−6.1% · COR-I, wk 56
How the trials differ: Opioid-antagonist + dopamine/NE reuptake inhibitor. COR programme; LIGHT CV outcomes (terminated early).
| Trial | Phase | N | Population | Comparator | Primary endpoint | Result / readout | Status | Source |
|---|---|---|---|---|---|---|---|---|
| COR-I no T2D |
Ph 3 | 1,742 | Obesity, Overweight | Placebo | Co-primary: Body Weight- Mean Percent Ch… | −6.1% (NB32) vs −1.3% (Lancet 2010) | Completed | NCT00532779↗ |
Phentermine–TopiramateQsymia
ApprovedApproved 2012 (Qsymia)
−9.8%
−9.8% · CONQUER top dose, wk 56
How the trials differ: Sympathomimetic + antiepileptic ER combination. CONQUER/EQUIP pivotal; SEQUEL 2-year extension.
| Trial | Phase | N | Population | Comparator | Primary endpoint | Result / readout | Status | Source |
|---|---|---|---|---|---|---|---|---|
| CONQUER + comorbidities |
Ph 3 | 2,487 | Obesity, Type 2 Diabetes | — | Percent Weight Loss From Baseline to Wee… | −9.8% (15/92) vs −1.2% (Lancet 2011) | Completed | NCT00553787↗ |
SetmelanotideImcivree
ApprovedApproved 2020 (POMC/LEPR/PCSK1); 2022 (BBS)
—
rare genetic obesity — ≥10% loss: 80% POMC / 45% LEPR (1 yr)
How the trials differ: MC4R agonist for rare genetic obesity only (not common obesity): POMC/PCSK1/LEPR deficiency, Bardet-Biedl syndrome.
| Trial | Phase | N | Population | Comparator | Primary endpoint | Result / readout | Status | Source |
|---|---|---|---|---|---|---|---|---|
| Ph3 POMC POMC deficiency |
Ph 3 | 15 | Pro-opiomelanocortin (POMC) Deficiency Obe… | Placebo | Percentage of Participants Who Reached ≥… wk 52 | ≥10% loss in 80% (8/10) at 1 yr (Lancet D&E 2020) | Completed | NCT02896192↗ |
OrlistatXenical · Alli
ApprovedApproved 1999 (Xenical) / 2007 OTC (Alli)
−10.2%
−10.2% · 1-yr RCT (Lancet 1998), 120 mg tid
How the trials differ: Intestinal lipase inhibitor (blocks ~30% dietary fat absorption). Landmark XENDOS 4-year trial; most pivotal trials predate ClinicalTrials.gov. Total 1-yr loss: −10.2% vs −6.1% with placebo (Lancet 1998) — placebo-adjusted ≈ −4%; XENDOS yr 1: −10.6 vs −6.2 kg.
| Trial | Phase | N | Population | Comparator | Primary endpoint | Result / readout | Status | Source |
|---|---|---|---|---|---|---|---|---|
| XENDOS 4-year · diabetes prevention |
Ph 3 | 3,305 | Obesity | Placebo | weight & diabetes incidence, 4 yr | −10.6 vs −6.2 kg (yr 1); diabetes −37% over 4 yr (Diabetes Care 2004) | Completed | — |
PhentermineAdipex-P
ApprovedApproved 1959; short-term use only
—
≈ −3–5% vs placebo (short-term; older data)
How the trials differ: Sympathomimetic appetite suppressant; oldest approved agent, indicated only for short-term (a few weeks) adjunct use. Sparse modern RCT/registry data.
| Trial | Phase | N | Population | Comparator | Primary endpoint | Result / readout | Status | Source |
|---|---|---|---|---|---|---|---|---|
| Short-term use ~12 weeks |
Ph 3 | — | Obesity (short-term adjunct) | Placebo | short-term weight loss | ≈ −3–5% vs placebo over ~12 wks (older literature; no single pivotal registry trial) | Completed | — |