GLP-1 Pipeline: What’s Coming

retatrutide —28.3% weight loss

StagePhase 3

TargetsGIPGLP-1glucagon triple agonist

Maker

Routeinjection (weekly)

Indicationsinvestigating obesity, type 2 diabetes, knee osteoarthritis, OSA, MASLD, chronic kidney disease (TRANSCEND-CKD)

Efficacy28.3% mean weight loss (~70.3 lb) at 80 wks, 12 mg (TRIUMPH-1 Phase 3); up to 30.3% at 104 wks in BMI ≥ 35 source

Beyond weight loss

• ✓ Knee osteoarthritis: 28.7% weight loss + WOMAC pain −75.8% (TRIUMPH-4, Dec 2025 · source)
• ✓ Obstructive sleep apnea: Apnea-hypopnea events -60.6% (about 36 fewer events/hr) at 12 mg as a TRIUMPH-1 secondary endpoint (ADA 2026). MASLD and CV-renal still under study (TRANSCEND-CKD). (TRIUMPH-1 (ADA 2026) · source)
• ⚠ Dysesthesia + UTI (safety): New dose-dependent signal absent in Phase 2: dysesthesia (abnormal/burning skin sensation) in 5.1%/12.3%/12.5% on 4/9/12 mg vs 0.9% placebo (TRIUMPH-1); up to 20.9% at 12 mg in TRIUMPH-4. UTIs elevated (up to 8.8% vs 5.3%). Mostly mild-moderate, usually resolved on treatment; AE discontinuation 11.3% at 12 mg vs 4.9% placebo. In T2D (TRANSCEND-T2D-1) the signal was milder: dysesthesia 2-4% vs 0% placebo, HR +~1 bpm. (TRIUMPH-1 topline (May 2026); TRIUMPH-4 (Dec 2025) · source)
• ~ Heart rhythm (early signal): In TRANSCEND-T2D-1 (n=403 treated) 7 patients had arrhythmias and 3 had major cardiovascular events vs 0 on placebo; resting pulse rose about 1 bpm. Because the glucagon arm can raise heart rate, it is the signal to watch, but investigators call the case counts too small to conclude anything. A dedicated cardiovascular-outcomes trial reads out ~2029. (TRANSCEND-T2D-1, Lancet 2026; STAT (ADA 2026) · source)
• ✓ Type 2 diabetes: TRANSCEND-T2D-1 (Lancet 2026, n=537, 40 wks, monotherapy in early T2D): HbA1c -1.94% (ETD -1.12% vs placebo) and -15.3% weight at 12 mg with no plateau; 82-89% reached HbA1c <7%; up to 64% hit the <=6.5% + >=10%-weight composite. Also improved triglycerides, non-HDL, and systolic BP. (TRANSCEND-T2D-1, Lancet 2026 · source)

Access & priceNot yet available

Key trials

• TRIUMPH-1 (Ph 3, obesity (no diabetes)) — Full data at ADA 2026 (n=2,339, 80 wks): 28.3% mean weight loss (~70.3 lb) at 12 mg (25.9% at 9 mg, 19.0% at 4 mg), 65.3% reached BMI <30; up to 30.3% (~85 lb) at 104 wks in the BMI ≥ 35 extension. Secondary endpoints at 12 mg: knee-osteoarthritis pain -73.1%, OSA events -60.6%, triglycerides -41%, systolic BP -12.3 mmHg. AE discontinuation 11.3% at 12 mg vs 4.9% placebo. source
• TRANSCEND-T2D-1 (Ph 3, type 2 diabetes) — Lancet 2026 (Bajaj et al., online 6 Jun; NCT06354660). 40-wk once-weekly monotherapy in drug-naive early T2D (n=537; baseline HbA1c 7.9%, BMI 35.8, diabetes 2.5 yr). HbA1c -1.94% at 12 mg vs -0.81% placebo (ETD -1.12%, p<0.0001); weight -15.3% at 12 mg vs -2.6% (no plateau); 82-89% reached HbA1c <7%, up to 64% hit the HbA1c<=6.5% + >=10%-weight composite. GI-predominant AEs; dysesthesia 2-4% (vs 0% placebo); no severe hypoglycaemia; pulse +~1 bpm. source
• TRIUMPH-4 (Ph 3, obesity + knee osteoarthritis) — 28.7% weight loss + large WOMAC knee-pain reduction at 68 wks. source
• TRANSCEND-CKD (Ph 3, chronic kidney disease) — Retatrutide in CKD; rationale/design/baseline published May 2026 (Nephrol Dial Transplant) — beyond-obesity expansion. source

Papers

• Triple-Hormone-Receptor Agonist Retatrutide for Obesity (Phase 2) — NEJM 2023
• Efficacy and safety of retatrutide, a GIP/GLP-1/glucagon agonist, in type 2 diabetes (TRANSCEND-T2D-1): a phase 3 trial — The Lancet 2026

On DSD

• Retatrutide: What TRIUMPH-1 Just Showed and the Black Market That Got There First

My takeThe favourite of body builders and wellness people everywhere. Seems very strong, so that many folks use it at low doses to minimize side effects. Raises heart rate more than tirzepatide, which worries me, personally.

cagrilintide + semaglutide CagriSema22.7% weight loss

StageFiled (FDA review)

TargetsGLP-1amylin GLP-1 + amylin analogue combination

Maker

Routeinjection (weekly)

Indicationsinvestigating obesity, type 2 diabetes

Efficacy22.7% weight loss at 68 wks (REDEFINE 1) — short of the ~25% the Street expected source

Beyond weight loss

• ✓ Type 2 diabetes: 15.7% weight loss in adults with obesity + T2D (REDEFINE 2) (REDEFINE 2, NEJM 2025 · source)
• ✓ Type 2 diabetes (head-to-head): REIMAGINE 2 (n=2,728, 68 wks): superior to semaglutide 2.4 mg on A1C (-1.91% vs -1.76%) and weight (-14.2% vs -10.2%). (REIMAGINE 2 (ADA 2026) · source)

Access & priceNot yet available

Key trials

• REDEFINE 1 (Ph 3, obesity (no diabetes)) — 22.7% weight loss at 68 wks; 23% of patients lost ≥30%. source
• REDEFINE 2 (Ph 3, obesity + T2D) — 15.7% weight loss in adults with obesity and type 2 diabetes. source
• REIMAGINE 2 (Ph 3, type 2 diabetes (head-to-head vs semaglutide)) — n=2,728; CagriSema 2.4/2.4 mg superior to semaglutide 2.4 mg at 68 wks: A1C up to -1.91% vs -1.76%, weight -14.2% vs -10.2% (43% lost >=15%, 24% >=20%). Published in Lancet Diab & Endo (7 Jun 2026). source
• REIMAGINE 1 (Ph 3, type 2 diabetes (monotherapy vs placebo)) — n=180; 40-wk monotherapy in T2D inadequately controlled on diet and exercise, vs placebo. Published in Lancet Diab & Endo (7 Jun 2026). source
• REIMAGINE 3 (Ph 3, type 2 diabetes (add-on to basal insulin vs placebo)) — n=270; 40-wk add-on to basal insulin in T2D, vs placebo. Published in Lancet (7 Jun 2026). source

Papers

• Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1) — NEJM 2025
• Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2) — NEJM 2025
• Efficacy and safety of once-weekly cagrilintide-semaglutide (CagriSema) in adults with type 2 diabetes inadequately controlled on diet and exercise (REIMAGINE 1): a phase 3a study — The Lancet Diabetes & Endocrinology 2026
• Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a phase 3 study — The Lancet Diabetes & Endocrinology 2026
• Cagrilintide-semaglutide (CagriSema) as an add-on to basal insulin in adults with type 2 diabetes (REIMAGINE 3): a phase 3 study — The Lancet 2026

My takeNovo's reavtion to the tirepatide effectiveness, promising, but may be quickly superceded by amycretin.

maridebart cafraglutide MariTide20% weight loss

StagePhase 3

TargetsGLP-1−GIP GLP-1 agonist + GIP receptor antagonist (peptide-antibody conjugate)

Maker

Routeinjection (monthly or less frequent)

Indicationsinvestigating obesity, type 2 diabetes

EfficacyUp to ~20% weight loss at 52 wks (Phase 2, obesity without T2D) source

Beyond weight loss

• ✓ Type 2 diabetes: ~17% weight loss + HbA1c up to −2.2% in T2D (Phase 2) (Phase 2, NEJM 2025 · source)

Access & priceNot yet available

Key trials

• MARITIME (Phase 3 program) (Ph 3, obesity) — Phase 3 launched 2026 following Phase 2 NEJM publication. source

Papers

• Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity (Phase 2) — NEJM 2025

survodutide —16.6% weight loss

StagePhase 3

TargetsglucagonGLP-1 dual agonist

Maker

Routeinjection (weekly)

Indicationsinvestigating obesity, MASH (FDA Breakthrough Therapy)

Efficacy16.6% weight loss (SYNCHRONIZE-1); 47-62% MASH improvement (Phase 2) source

Beyond weight loss

• ✓ MASH / liver fibrosis: MASH improvement in 47-62% vs 14% placebo — FDA Breakthrough Therapy. The glucagon arm is liver-active. (Phase 2, NEJM 2024 · source)

Access & priceNot yet available

Key trials

• SYNCHRONIZE-1 (Ph 3, obesity) — 16.6% mean weight loss at 76 wks (efficacy estimand) vs 3.2% placebo (p<0.0001); ~39.2 lb (17.8 kg); 85.1% achieved >=5% loss; loss was predominantly fat, minimal lean mass. Full data at ADA 2026. source
• LIVERAGE (Ph 3, MASH + fibrosis) — MASH/fibrosis Phase 3; readout expected late 2026. source

Papers

• A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis — NEJM 2024

brenipatide —

StagePhase 3

TargetsGIPGLP-1 agonist (monthly; optimized for neuroscience, not weight loss)

Maker

Routeinjection (monthly)

Indicationsinvestigating alcohol use disorder, bipolar disorder, smoking cessation

EfficacyNot a weight-loss drug — targets addiction/psychiatric endpoints; weight-loss data limited

Beyond weight loss

• ⋯ Alcohol use disorder: Purpose-built for addiction (neuro-optimized, monthly); Phase 3 RENEW-ALC (RENEW-ALC (recruiting) · source)
• ⋯ Bipolar / smoking cessation: Psychiatric & addiction endpoints — the whole point of the molecule, not weight (Phase 2/3 program)

Access & priceNot yet available; earliest approval ~2028

Key trials

• RENEW-ALC-1 / RENEW-ALC-2 (Ph 3, alcohol use disorder) — Phase 3 in moderate-to-severe AUD / hazardous drinking (~56 wks). source

On DSD

• Brenipatide vs Tirzepatide: What the Comparison Actually Looks Like in 2026
• Brenipatide: Eli Lilly's Monthly GLP-1 for Alcohol Use Disorder

My takeThis is a very exciting compound. Anything that helps people stay sober would have huge societal benefit. The monthly dosing would make sticking to the protocol much easier.

amycretin (INN: zenagamtide) —22% weight loss

StagePhase 2

TargetsamylinGLP-1 receptor agonist (oral & injectable)

Maker

Routeoral / injection

Indicationsinvestigating obesity, type 2 diabetes

Efficacy~22% mean weight loss at 36 wks (Phase 1b/2a, subcutaneous, obesity; up to 24% at the top dose) source

Beyond weight loss

• ✓ Type 2 diabetes: Phase 2 (36 wks): A1C up to -1.71 pp and up to 14.6% weight loss on once-weekly injectable; 89% reached A1C <7%. (Phase 2 T2D (ADA 2026, zenagamtide) · source)

Key trials

• Phase 2 T2D (zenagamtide) (Ph 2, type 2 diabetes (once-weekly injectable)) — n=262 (225 drug/37 placebo), 36 wks: A1C up to -1.71 pp (40 mg) vs -0.14 placebo, up to 89.1% reached A1C <7%, weight loss up to 14.6%. Presented at ADA 2026 under the INN zenagamtide. source

mazdutide —16.65% weight loss

StagePhase 3

TargetsglucagonGLP-1 dual agonist

Maker

Routeinjection

Indicationsinvestigating obesity (China-first)

Efficacy-16.65% mean weight loss at 60 wks (GLORY-2 Phase 3, JAMA, 9 mg; 42% lost >=20%); 14.8% at 6 mg (GLORY-1, NEJM) source

Beyond weight loss

• ✓ Type 2 diabetes (head-to-head): DREAMS-3 (n=349, China, 32 wks): superior to semaglutide 1 mg on glycemia and weight (HbA1c -2.03% vs -1.84%; weight -10.29% vs -6.00%). (DREAMS-3 (ADA 2026) · source)

Key trials

• GLORY-2 (Ph 3, obesity (China; once-weekly 9 mg)) — n=461 Chinese adults with obesity (16% with T2D), 60 wks: mazdutide 9 mg -16.65% mean body weight vs -1.50% placebo (difference -15.15%). 84% lost >=5%, 70% >=10%, 57% >=15%, 42% >=20%. SBP -9.8 mm Hg, triglycerides -21%, non-HDL -14.6%. GI AEs common (vomiting 53%, nausea 47%); 2.9% discontinued for AEs. Published in JAMA. source
• DREAMS-3 (Ph 3, type 2 diabetes + obesity (head-to-head vs semaglutide)) — n=349 Chinese adults, early T2D + obesity, 32 wks: mazdutide 6 mg beat semaglutide 1 mg — HbA1c -2.03% vs -1.84%, weight -10.29% vs -6.00%, composite (A1c<7% + >=10% weight) 48% vs 21%. Presented at ADA 2026. source

Papers

• Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial — JAMA 2026

VK2735 —14.7% weight loss

StagePhase 3

TargetsGIPGLP-1 dual agonist (injectable + oral in development)

Maker

Routeinjection (weekly); oral (daily) in development

Indicationsinvestigating obesity, type 2 diabetes

Efficacy~14.7% at 13 wks (Phase 2 VENTURE, subcutaneous); oral VK2735 ~12.2% at 13 wks (VENTURE-Oral) source

eloralintide —20.1% weight loss

StagePhase 3

Targetsamylin selective amylin receptor agonist

Maker

Routeinjection (weekly)

Indicationsinvestigating obesity

EfficacyUp to 20.1% at 48 wks (Phase 2, NCT06230523, 263 adults); 9.5%-20.1% across doses vs 0.4% placebo, max -21.3 kg at 9 mg. Selective amylin agonist, no GLP-1. source

Key trials

• Phase 2 (NCT06230523) (Ph 2, obesity/overweight, no type 2 diabetes) — 263 adults; up to 20.1% weight loss at 48 wks vs 0.4% placebo (efficacy estimand); max -21.3 kg at 9 mg. GI/fatigue AEs mild-to-moderate, lower with slower dose escalation. source

Papers

• Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial — The Lancet 2025

berobenatide (MET-097i / PF-08653944) —14.1% weight loss

StagePhase 2

TargetsGLP-1 ultra-long-acting GLP-1 receptor agonist

Maker

Routeinjection (monthly potential)

Indicationsinvestigating obesity, type 2 diabetes

EfficacyUp to 14.1% placebo-adjusted at 28 wks (weekly 1.2 mg, VESPER-1) and 12.3% monthly (VESPER-3); longer follow-up reached ~15.9% on the highest weekly dose at 8 mo with no plateau (ADA 2026) source

Key trials

• VESPER-1 (Ph 2, obesity / overweight (weekly dosing)) — Up to 14.1% placebo-adjusted weight loss at 28 wks (1.2 mg once-weekly); individual responses up to 26.5%. Full data at ADA 2026. source
• VESPER-2 (Ph 2, obesity + type 2 diabetes (weekly dosing)) — 28-wk data in adults with overweight/obesity and T2D presented at ADA 2026; dose-level percentages pending full presentation. source
• VESPER-3 (Ph 2, obesity / overweight) — 12.3% placebo-adjusted weight loss at 28 wks with monthly dosing. source

ribupatide (KAI-9531 / HRS9531) —23.6% weight loss

StagePhase 3

TargetsGIPGLP-1 dual agonist (Kailera also has a separate triple agonist)

Maker

Routeinjection (weekly)

Indicationsinvestigating obesity, type 2 diabetes

Efficacy23.6% weight loss at 36 wks (Phase 2, 8 mg); 19.2% in China Phase 3 (6 mg, 48 wks) source

Key trials

• KaiNETIC (global Phase 3) (Ph 3, obesity) — Global Phase 3 program; China Phase 3 (HRS9531-301) showed 19.2% at 6 mg / 48 wks. source

efpeglenatide —9.8% weight loss

StagePhase 3

TargetsGLP-1 long-acting GLP-1 receptor agonist (exendin-4 based, Lapscovery platform)

Maker

Routeinjection

Indicationsinvestigating obesity, type 2 diabetes

Efficacy~9.8% mean weight loss at 40 wks (Phase 3 topline, non-diabetic adults, 2025) source

Beyond weight loss

• ✓ Cardiovascular: Fewer major cardiovascular events (3-point MACE) vs placebo in high-risk T2D (AMPLITUDE-O, NEJM 2021 (n=4,076) · source)
• ✓ Kidney: Slower decline in kidney function / less albuminuria progression (AMPLITUDE-O, NEJM 2021 · source)

Access & priceNot yet available (Korea filing first)

Key trials

• AMPLITUDE-O (Ph 3, type 2 diabetes, high CV/renal risk) — Cut major cardiovascular events and slowed kidney decline vs placebo in 4,076 patients; the basis for its CV/renal differentiation. source
• Phase 3 obesity (Korea) (Ph 3, obesity (no diabetes)) — ~9.8% mean weight loss at 40 wks (n=448); full publication pending. source

Papers

• Cardiovascular and Renal Outcomes with Efpeglenatide in Type 2 Diabetes (AMPLITUDE-O) — NEJM 2021

My takeThe cardiovascular and kidney outcomes pedigree is real (AMPLITUDE-O), but the obesity efficacy is modest next to tirzepatide and retatrutide, and it's a Korea-first launch with no US filing yet. Worth watching as the value and access play, not the weight-loss leader.

Watch list (earlier stage)

Molecule	Maker	Targets	Stage	Weight loss	What's next
aleniglipron (GSBR-1290) —		GLP-1	Early / watch	16.3%	Heading to Phase 3 (oral pill) (2026)
pemvidutide —		glucagonGLP-1	Early / watch	15.6%	Phase 3 planning; also a positive MASH (liver) trial (2026)
petrelintide —		amylin	Early / watch	10.7%	Advancing to Phase 3; petrelintide + CT-388 combo Phase 2 starting (2026)
MET-233i —		amylin	Early / watch	8.4%	MET-233i + MET-097i once-monthly combo 12-wk topline (2026)
ABBV-295 (GUB014295) —		amylin	Early / watch	7.75%	Advancing toward Phase 2 (2026)
AZD6234 —		amylin	Early / watch	—	Phase 2 weight-loss readout (2026 (H1))

Weight loss = peak mean result at the approved (or trial) obesity dose. Diabetes brands and lower doses come in below this; see each drug's card for the per-product breakdown.