GLP-1 Pipeline: What’s Coming

retatrutide —28.3% mean weight change80 wk · obesity, no T2D · efficacy estimand · raw change

StagePhase 3 complete

TargetsGIPGLP-1glucagon triple agonist

Maker

Routeinjection (weekly)

Indicationsinvestigating obesity, type 2 diabetes, knee osteoarthritis, OSA, MASLD, chronic kidney disease (TRANSCEND-CKD), cardiovascular outcomes, chronic low back pain

Efficacy28.3% mean weight loss (~70.3 lb) at 80 wks on 12 mg vs 2.2% placebo (TRIUMPH-1 Phase 3, efficacy estimand); on the treatment-regimen estimand it is 25.0% vs 3.9%. Up to 30.3% at 104 wks in BMI 35+. Harder populations lose less: 22.6% in severe obesity with established cardiovascular disease (TRIUMPH-3) and 20.8% with type 2 diabetes (TRIUMPH-2; 18.8% on the treatment-regimen estimand), both at 80 wks on 12 mg. source

Beyond weight loss

• ✓ Knee osteoarthritis: 28.7% weight loss and WOMAC knee pain down 75.8% at 12 mg — but placebo fell 40.3%, so roughly half the pain improvement is not attributable to the drug. TRIUMPH-1 (NEJM 2026) shows the same pattern in its 574 participants with knee osteoarthritis: the WOMAC pain score (0-10 scale) fell 3.6 points at 12 mg and 1.9 on placebo, a 1.8-point difference. The paper puts the reduction at up to 61.6%; Lilly's June release had said 73.1%. (TRIUMPH-4, Dec 2025; TRIUMPH-1, NEJM 2026 · source)
• ✓ Obstructive sleep apnea: Sleep apnea was a primary endpoint of TRIUMPH-1 (NEJM 2026), tested in 243 participants with obstructive sleep apnea: the apnea-hypopnea index fell 31.7 events per hour at 12 mg and 34.3 at 9 mg, against 9.9 on placebo, so about 22 and 24 fewer events per hour than placebo. The 9 mg dose did at least as well as 12 mg. The paper puts the reduction at up to 57.3%; Lilly's June release had said 60.6%. MASLD and CV-renal still under study (TRANSCEND-CKD). (TRIUMPH-1, NEJM 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 (7.5-8.7% vs 5.3%; 92% of cases in women). Low blood pressure was reported in 8.8% at 12 mg vs 0.9% on placebo, more often in people already taking blood-pressure drugs. Mostly mild-moderate, usually resolved on treatment; AE discontinuation 11.1% at 12 mg vs 4.6% placebo. The TRIUMPH-1 paper also shows how often the top dose had to be cut back: 22.5% of people on 12 mg had a permanent dose reduction (vs 0.5% on placebo): 9.8% for perceived excessive weight loss, 6.2% for stomach symptoms and 5.5% for reaching a BMI of 22 or less. Cuts were one-way, to the next lower dose, and 5.3% stopped treatment because they had lost enough or too much weight. By week 80 only 54.0% were still on their assigned 12 mg dose; 11.2% were on 9 mg and 5.7% on 4 mg. Those people still count in the 12 mg results, including the 28.3% headline. In T2D (TRANSCEND-T2D-1) the signal was milder: dysesthesia 2-4% vs 0% placebo, HR +~1 bpm. The two July 2026 trials came in lower at the top dose — 7.3% in TRIUMPH-2 and 6.4% in TRIUMPH-3 vs 0.7% and 1.3% on placebo — so the signal is consistent and dose-related but not as large as TRIUMPH-1 suggested. The TRIUMPH-2 paper (Lancet 2026) adds low blood pressure in 6.3% at 12 mg vs 0.3% on placebo (post-hoc) and three cases of adjudicated pancreatitis, all on retatrutide; none of its dysesthesia cases was severe or serious. Discontinuation for side effects was highest in the sickest group: 13.5% at 12 mg in TRIUMPH-3 vs 4.8% placebo. (TRIUMPH-1 (NEJM 2026); TRIUMPH-2 (Lancet 2026); TRIUMPH-4 (Dec 2025); TRIUMPH-3 topline (Jul 2026) · source)
• ~ Heart and circulation (signal): TRIUMPH-3 put retatrutide into 1,949 people who already had cardiovascular disease, and nothing alarming surfaced over 80 weeks — but the trial cannot show benefit either, and Lilly says so: cardiovascular events "occurred less frequently than anticipated" in both arms. Pre-specified, retatrutide had 44 broad events (death, heart attack, stroke, heart failure, revascularisation) against 52 on placebo, a hazard ratio of 0.82 with a confidence interval of 0.55 to 1.22 that crosses 1. On the narrower measure — cardiovascular death, heart attack, stroke — there were slightly more on the drug: 27 vs 23, hazard ratio 1.12 (0.64 to 1.96). Both results are compatible with a meaningful benefit and with a modest harm. The friendlier numbers Lilly also reports (0.73 and 0.92) come from an analysis that was not pre-specified. Risk factors did move clearly at the top dose: triglycerides -37.0%, non-HDL cholesterol -16.5%, systolic BP -9.3 mmHg, hsCRP -51.2%. The earlier worry stands unresolved rather than settled: because the glucagon arm can raise heart rate, in TRANSCEND-T2D-1 7 of 403 treated patients had arrhythmias and 3 had major cardiovascular events against none on placebo, and resting pulse rose about 1 bpm. The dedicated cardiovascular-outcomes trial reads out around 2029. (TRIUMPH-3 topline (Jul 2026); TRANSCEND-T2D-1, Lancet 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. TRIUMPH-2 (Lancet 2026) confirms this at scale and at 80 weeks in people already on oral diabetes drugs: from a baseline HbA1c of 7.7%, reductions of 1.38 to 1.50 points against 0.45 on placebo (treatment-regimen estimand), with 72% reaching HbA1c ≤ 6.5% at 12 mg vs 29%, alongside 18.8% weight loss. The authors put the smaller HbA1c drop than TRANSCEND-T2D-1 down to longer-standing diabetes and a lower starting HbA1c. (TRANSCEND-T2D-1, Lancet 2026; TRIUMPH-2, Lancet 2026 · source)

Access & priceNot yet available

Key trials

• TRIUMPH-1 (Ph 3, obesity (no diabetes)) — Published in NEJM on 29 Sep 2026 (NCT05929066, n=2,339, 80 wks, mean BMI 40, 77% with BMI ≥ 35). The paper's primary weight analysis uses the treatment-regimen estimand, which counts everyone randomised whether or not they stayed on the drug: -25.0% at 12 mg, -23.7% at 9 mg, -17.6% at 4 mg vs -3.9% on placebo. On the efficacy estimand (people who stayed on treatment) the figures are 28.3%, 25.9% and 19.0% vs 2.2%. At 12 mg, 36.9% lost at least 30% of their weight and 57.1% reached BMI <30 (treatment-regimen). In the 104-week extension for people with BMI ≥ 35, those kept on 12 mg reached -29.9% (-30.3% on the efficacy estimand, n=109). Knee pain and sleep apnea were primary endpoints, each tested in a subgroup. Knee osteoarthritis (n=574): the WOMAC pain score (0-10 scale) fell 3.6 points at 12 mg vs 1.9 on placebo, a 1.8-point difference. Sleep apnea (n=243): the apnea-hypopnea index fell 31.7 events per hour at 12 mg and 34.3 at 9 mg vs 9.9 on placebo, differences of 21.9 and 24.4. The paper's own percentage figures, up to 61.6% less knee pain and 57.3% fewer apnea events, are lower than the 73.1% and 60.6% in Lilly's June release. Also at 12 mg: triglycerides -38.0%, systolic BP -10.4 mmHg, hsCRP -62.6%, and 89-93% of people with prediabetes returned to normal glucose vs 54.2% on placebo. AE discontinuation 11.1% at 12 mg vs 4.6% placebo. source
• TRIUMPH-2 (Ph 3, obesity/overweight + type 2 diabetes) — Published in The Lancet on 29 Sep 2026 (NCT05929079, n=1,152, 80 wks, mean age 55, BMI 38.2, HbA1c 7.7%, diabetes for a median 5.6 years, 92% on oral glucose-lowering drugs). The paper's primary analysis uses the treatment-regimen estimand, which counts everyone randomised whether or not they stayed on the drug: -18.8% at 12 mg, -16.8% at 9 mg, -11.9% at 4 mg vs -5.1% on placebo (difference -13.8 points at 12 mg). The -20.8% / -19.1% / -12.7% vs -4.0% figures in Lilly's July topline are the efficacy estimand (people who stayed on treatment). At 12 mg, 47% lost at least 20% of their weight and 31% at least 25%; in people with BMI ≥ 35 the loss was -21.9% (-23.4% efficacy estimand). HbA1c fell 1.45 / 1.50 / 1.38 points vs 0.45 on placebo, and 72% at 12 mg reached HbA1c ≤ 6.5% vs 29%. Also at 12 mg: systolic BP -9.7 vs -2.7 mmHg, triglycerides -35.6%, non-HDL cholesterol -16.5%, hsCRP -56.1%. Safety: AE discontinuation 7.7% (12 mg) / 11.6% (9 mg) / 3.8% (4 mg) vs 4.9%; dysesthesia 7.3% / 5.6% / 4.5% vs 0.7%; low blood pressure 6.3% at 12 mg vs 0.3% (post-hoc); pancreatitis in three people, all on retatrutide; adjudicated heart attacks, strokes and cardiovascular deaths balanced (4 / 4 / 3 vs 4). Seven people died, six on retatrutide and one on placebo; investigators judged none related to the drug, and an independent committee classed three of the six as cardiovascular deaths. No active comparator and no body-composition measurement. source
• TRIUMPH-3 (Ph 3, severe obesity + established cardiovascular disease) — Topline 23 Jul 2026 (NCT05882045, n=1,949 randomised, 80 wks). Severe obesity (BMI ≥ 35) with established cardiovascular disease, with or without type 2 diabetes. Weight -22.6% at 12 mg (-55.8 lb) and -21.6% at 9 mg vs -3.2% placebo, from a baseline of 111.4 kg / BMI 40.4 (efficacy estimand). At the top dose: triglycerides -37.0%, non-HDL cholesterol -16.5%, systolic BP -9.3 mmHg, waist -19.0 cm, hsCRP -51.2%. Cardiovascular events were too few to interpret (see the cardiovascular row below). Dysesthesia 6.4% on both doses vs 1.3% placebo; AE discontinuation 13.5% (12 mg) / 9.8% (9 mg) vs 4.8%. Detailed results to be presented and published; not yet peer-reviewed. 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/overweight + knee osteoarthritis) — Obesity + knee OA, 68 wks: weight -28.7% at 12 mg / -26.4% at 9 mg vs -2.1% placebo. WOMAC knee-pain -74.3% (12 mg) / -75.8% (9 mg) vs -40.3% placebo, with physical-function subscale -73.7% / -71.8% vs -35.6%. Pain-free at 68 wks: 12.0% (12 mg) / 14.1% (9 mg) vs 4.2% placebo (>1 in 8 on drug). Detailed data presented at ADA 2026; peer-reviewed publication pending. 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
• Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity (TRIUMPH-1) — NEJM 2026
• Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial — The Lancet 2026

On DSD

• More Than One in Five on Top-Dose Retatrutide Had the Dose Cut, Most Often for Losing Too Much Weight
• Retatrutide vs Zepbound: Is Lilly's Next Weight-Loss Shot Worth Waiting For?
• Retatrutide: What TRIUMPH-1 Just Showed and the Black Market That Got There First
• Does Retatrutide Have a Brand Name Yet?
• Retatrutide Cost: No Price Yet, and My Estimate Is $450 to $650 a Month

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 CagriSema20.4% mean weight change68 wk · obesity, no T2D · treatment-policy · raw change

StageFiled (FDA review)

TargetsGLP-1amylin GLP-1 + amylin analogue combination

Maker

Routeinjection (weekly)

Indicationsinvestigating obesity, type 2 diabetes

Efficacy20.4% weight loss at 68 wks vs 3.0% placebo (REDEFINE 1, treatment-policy estimand — the figure in the published NEJM paper; 22.7% on the efficacy estimand) — short of the ~25% the Street expected. source

Beyond weight loss

• ✓ Type 2 diabetes: 13.7% weight loss vs 3.4% placebo in adults with obesity + T2D (REDEFINE 2, treatment-policy estimand as published; 15.7% on the efficacy estimand). (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)
• ✓ Type 2 diabetes (head-to-head vs tirzepatide): REIMAGINE 5 (60 wks): CagriSema 1.0/1.0 mg beat tirzepatide 5 mg on weight (12.42% vs 9.12%) and matched it on A1C (-1.71% vs -1.67%). The comparator is tirzepatide's lowest maintenance dose — Novo's own slide notes that about half of global tirzepatide volume is 5 mg or below. (REIMAGINE 5 (topline, Sep 2026) · source)

Access & priceNot yet available

Key trials

• REDEFINE 1 (Ph 3, obesity (no diabetes)) — 20.4% weight loss at 68 wks vs 3.0% placebo (treatment-policy estimand as published in NEJM; 22.7% on the efficacy estimand). 23% of patients lost 30% or more. source
• REDEFINE 2 (Ph 3, obesity + T2D) — 13.7% weight loss vs 3.4% placebo in adults with obesity and type 2 diabetes (treatment-policy estimand as published; 15.7% on the efficacy estimand). 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
• REIMAGINE 5 (Ph 3, type 2 diabetes (head-to-head vs tirzepatide)) — First direct CagriSema-vs-tirzepatide data. At 60 wks, CagriSema 1.0/1.0 mg gave 12.42% weight loss vs 9.12% for tirzepatide 5 mg (superior) and an A1C drop of 1.71% vs 1.67% (non-inferior). Mean baseline BMI 37.2, A1C 8.1%. Two caveats: the comparator is tirzepatide 5 mg, the lowest maintenance dose, not the 10 or 15 mg doses; and these are efficacy-estimand figures, so they are not comparable to the treatment-policy numbers published for REDEFINE 1 and 2. Topline and investor-deck only — no participant numbers, no adverse-event tables, not published. source
• REDEFINE 9 (Ph 3, obesity (lower doses vs placebo)) — Tested whether CagriSema works at lower doses with fewer titration steps. At 68 wks, the 1.0/1.0 mg dose gave 20.95% weight loss vs 2.0% placebo (efficacy estimand). The higher 1.7/1.7 mg dose gave 20.75% — slightly less — a number Novo reported only in a footnote of its Capital Markets Day slides, not in the press release. Novo's on-slide explanation is that the protocol allowed flexible dosing. Discontinuation for any adverse event was 4.9% on 1.0/1.0 mg, 2.9% on 1.7/1.7 mg and 4.9% on placebo, so the flat dose-response is not explained by people dropping off the higher dose. Topline and investor-deck only, not published. 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

On DSD

• CagriSema vs Zepbound: The New Combo Couldn't Prove It Matches the Drug I'm On
• Does CagriSema Have a Brand Name Yet?
• Is CagriSema Covered by Medicare?

My takeNovo's reaction to tirzepatide's effectiveness, promising, but may be quickly superseded by amycretin.

maridebart cafraglutide MariTide16.2% mean weight change52 wk · obesity, no T2D · treatment-policy · raw change

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

Efficacy12.3% to 16.2% weight loss at 52 wks vs 2.5% placebo (Phase 2, obesity without T2D, treatment-policy estimand as published in NEJM). Amgen's earlier topline release quoted ~20% on the efficacy estimand. source

Beyond weight loss

• ✓ Type 2 diabetes: 8.4% to 12.3% weight loss and HbA1c down 1.2 to 1.6 percentage points in type 2 diabetes (Phase 2, as published in NEJM). (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 —13.0% mean weight change76 wk · obesity, no T2D · treatment-regimen · raw change

StagePhase 3

TargetsglucagonGLP-1 dual agonist

Maker

Routeinjection (weekly)

Indicationsinvestigating obesity, MASH (FDA Breakthrough Therapy)

Efficacy13.0% mean weight loss at 76 wks on 6.0 mg vs 5.4% placebo (SYNCHRONIZE-1, treatment-regimen estimand — the primary analysis in the published NEJM paper). Under the efficacy estimand the same trial reads 16.6% vs 3.2%; the two pairs are not interchangeable. 71.9% lost 5% or more vs 46.3% on placebo. source

Beyond weight loss

• ✓ MASH / liver fibrosis: MASH improved in 47% at 2.4 mg and 62% at 4.8 mg vs 14% on placebo — but 43% at the highest 6.0 mg dose, so the response is not more-is-better. FDA Breakthrough Therapy Designation; the glucagon arm is liver-active. (Phase 2, NEJM 2024 · source)

Access & priceNot yet available

Key trials

• SYNCHRONIZE-1 (Ph 3, obesity) — 13.0% mean weight loss at 76 wks on 6.0 mg vs 5.4% placebo (treatment-regimen estimand, the published primary), with 71.9% losing 5% or more vs 46.3%. On the efficacy estimand the same trial reads 16.6% vs 3.2%, with 85.1% vs 38.8% losing 5% or more. Published NEJM 7 Jun 2026. source
• SYNCHRONIZE-2 (Ph 3, obesity with type 2 diabetes) — n=752 adults with type 2 diabetes and a BMI of 27 or above, 76 weeks, weekly survodutide 3.6 mg or 6.0 mg vs placebo. The published primary analysis in NEJM uses the treatment-regimen estimand, which counts everyone randomised whether or not they stayed on the drug: 8.2% mean weight loss on 3.6 mg and 9.8% on 6.0 mg vs 3.9% on placebo, with 57.6% and 64.5% losing 5% or more vs 35.1%. That is the like-for-like comparison with SYNCHRONIZE-1's 13.0% vs 5.4% in people without diabetes. The company release led with the efficacy estimand, for people who stayed on treatment: up to 13.1% vs 3.1%, and 79.3% vs 32.7% losing 5% or more. HbA1c fell 0.9 points on 3.6 mg and 0.8 on 6.0 mg vs 0.2 on placebo, from a 7.4% baseline, in the paper's abstract; the release gives 1.21 vs 0.03. Gastrointestinal side effects were reported by 72.8% and 77.7% vs 38.6% on placebo, and the release says 18% stopped survodutide because of them vs 1.2%, mostly during dose escalation. Published in NEJM (Wharton et al.) and presented at EASD on 1 Oct 2026. Figures are from the paper's abstract and the company release; the full paper has not been read. source
• LIVERAGE (Ph 3, MASH + fibrosis) — MASH/fibrosis Phase 3, NCT06632444, n=1,800, still recruiting — primary completion Dec 2031. LIVERAGE-Cirrhosis (NCT06632457, n=1,590) runs to Jun 2029. Neither is a near-term readout. source
• SYNCHRONIZE-CVOT (Ph 3, cardiovascular outcomes) — NCT06077864, n=5,531, event-driven CV safety trial. Primary completion 16 Jun 2026. Results not yet published. source

Papers

• Survodutide Once Weekly in Adults with Obesity and Type 2 Diabetes (SYNCHRONIZE-2) — NEJM 2026
• Survodutide Once Weekly for the Treatment of Adults with Obesity (SYNCHRONIZE-1) — NEJM 2026
• A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis — NEJM 2024

brenipatide —

StagePhase 3

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

Maker

Routeinjection (weekly)

Indicationsinvestigating alcohol use disorder, major depressive disorder, bipolar disorder, smoking relapse prevention, opioid use disorder, schizophrenia, IBS-C, IBS-D, asthma, COPD

EfficacyNot a weight-loss drug — it targets addiction and psychiatric endpoints. No efficacy data has been published in any indication. The first dedicated body-weight study (NCT07476118, Phase 1b, 150 participants with overweight or obesity) does not complete until Feb 2027, so no weight number can honestly be quoted yet. source

Beyond weight loss

• ⋯ Alcohol use disorder: Purpose-built for addiction (neuro-optimized, weekly dosing); Phase 3 RENEW-ALC (RENEW-ALC (recruiting) · source)
• ⋯ Smoking relapse prevention: Not smoking cessation itself — enrolls people who already quit and tests whether brenipatide helps the quit stick (NCT07223840 (Phase 2, recruiting since Nov 2025) · source)
• ⋯ COPD: Newest addition to the pipeline (registered Aug 2026); GIP/GLP-1 receptors are expressed in lung tissue and obesity independently worsens COPD (NCT07759245 (Phase 2, not yet recruiting) · source)
• ⋯ Bipolar disorder / schizophrenia / IBS / opioid use disorder: Psychiatric & addiction endpoints — the whole point of the molecule, not weight (Phase 2 program, all recruiting)

Access & priceNot yet available; earliest approval ~2028

Key trials

• RENEW-ALC-1 (Ph 3, alcohol use disorder) — NCT07219966, n=1,100, recruiting since 15 Oct 2025, primary outcome up to 56 weeks. source
• RENEW-ALC-2 (Ph 3, alcohol use disorder) — NCT07219953, n=1,100, recruiting since 16 Oct 2025 — a separate registration from ALC-1. source
• RENEW-MDD-1 (Ph 3, major depressive disorder) — NCT07412756, n=1,000, recruiting since 9 Feb 2026 — a second Phase 3 indication. source
• Phase 1b body-weight study (Ph 1, overweight / obesity) — NCT07476118, n=150, started 18 Mar 2026, primary completion Feb 2027. The only study measuring body weight. source
• RENEW-MDD-2 (Ph 3, major depressive disorder) — NCT07775300, a second Phase 3 MDD registration alongside RENEW-MDD-1. source
• Smoking relapse prevention (Ph 2, smoking relapse prevention) — NCT07223840, recruiting since 3 Nov 2025. Enrolls adults who have already quit smoking cigarettes and want to avoid relapse — not a smoking-cessation trial. source
• Opioid use disorder (Ph 2, opioid use disorder) — NCT07420283, recruiting since 13 Feb 2026. source
• RENEW-Bipolar-1 (Ph 2, bipolar disorder) — NCT07286175, recruiting since 24 Nov 2025. source
• Schizophrenia study (Ph 2, schizophrenia) — NCT07410507, recruiting since 10 Feb 2026. source
• Asthma study (Ph 2, asthma) — NCT07219173, uncontrolled moderate-to-severe asthma, recruiting since 22 Oct 2025. source
• IBS-C study (Ph 2, IBS-C) — NCT07545772, irritable bowel syndrome with constipation, recruiting since 29 Apr 2026. source
• IBS-D study (Ph 2, IBS-D) — NCT07545759, irritable bowel syndrome with diarrhea, recruiting since 6 May 2026. source
• COPD study (Ph 2, COPD) — NCT07759245, moderate-to-severe COPD. Newest addition to the pipeline, registered Aug 2026 — the trial that surfaced in the 2026-09-09 morning scan. 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
• Brenipatide Side Effects: 13 Trials, No Results Yet

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

amycretin (INN: zenagamtide) —22.0% mean weight change36 wk · obesity, no T2D · raw change

StagePhase 3

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 (once-weekly SC): Phase 2 (n=262, 36 wks): A1C -0.9 to -1.7 pp across 0.4-40 mg doses, significant vs placebo across the dose range (The Lancet, 30 Jul 2026). ADA 2026 presentation additionally reported up to 14.6% weight loss and up to 89.1% reaching A1C <7% (not in the Lancet abstract). (Phase 2 T2D SC (The Lancet 2026; ADA 2026) · source)
• ✓ Type 2 diabetes (once-daily oral): Phase 2 (n=186, 36 wks): once-daily oral 6, 25, and 50 mg cut A1C by 0.9, 1.3, and 1.4 pp, all significant vs placebo; GI adverse events 26-47% by dose vs 23% placebo. Weight loss not reported in the abstract. (Phase 2 T2D oral, The Lancet 2026 · source)

Key trials

• Phase 2 T2D, once-weekly SC (zenagamtide) (Ph 2, type 2 diabetes (once-weekly injectable)) — n=262 (225 drug / 37 placebo), 36 wks, once-weekly maintenance doses 0.4-40 mg: A1C -0.9 pp at 0.4 mg to -1.7 pp at 40 mg (treatment difference vs placebo -0.77 to -1.56 pp, significant across the dose range; baseline 7.8%). Most adverse events gastrointestinal, mild to moderate; serious AEs in 21/261 (8%) across all groups incl. placebo; no deaths. Weight loss not reported in the abstract — the up-to-14.6% weight loss and up-to-89.1% reaching A1C <7% figures are from the ADA 2026 presentation. Published in The Lancet 30 Jul 2026 (NCT06542874). source
• Phase 2 T2D, once-daily oral (zenagamtide) (Ph 2, type 2 diabetes (once-daily oral)) — n=186 (54 on 6 mg / 51 on 25 mg / 51 on 50 mg / 30 placebo), 36 wks: A1C -0.9, -1.3, and -1.4 pp from a 7.9-8.1% baseline (treatment difference vs placebo -0.5, -0.99, and -1.09 pp; all significant). GI adverse events in 26%, 41%, and 47% by dose vs 23% on placebo; serious AEs in 7/186 (4%), none on placebo; no deaths. Weight loss not reported in the abstract. Published in The Lancet 30 Jul 2026 (NCT06542874). source
• AMAZE (Phase 3 obesity programme) (Ph 3, obesity) — AMAZE 1 (NCT07339423, n=1,150) started 24 Feb 2026 and is recruiting, with AMAZE 2, 3, 4, 5, 6 and 12 also recruiting and 7, 8 and 13 registered. Note Novo's separate type 2 diabetes Phase 3 is the one still described as planned for H2 2026 — the obesity programme began months earlier. source
• HF-POLARIS (Phase 3, heart failure) (Ph 3, heart failure) — NCT07567001, n=5,610, recruiting since 11 May 2026. source

Papers

• Efficacy and safety of once-daily oral zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in adults with type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial — The Lancet 2026
• Efficacy and safety of once-weekly subcutaneous zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial — The Lancet 2026

mazdutide —16.65% mean weight change60 wk · obesity, no T2D · raw change

StageApproved · China

TargetsglucagonGLP-1 dual agonist

Maker

Routeinjection

Indicationsapproved for chronic weight management (China, NMPA, Jun 2025), type 2 diabetes glycaemic control (China, NMPA, Sep 2025); investigating obesity and type 2 diabetes outside China (no US filing)

Efficacy-16.65% mean weight loss at 60 wks on 9 mg (GLORY-2 Phase 3, JAMA, all-treated; 42% lost 20% or more); in GLORY-1 the 6 mg dose gave -14.01% at week 48 on the treatment-policy estimand, or -14.84% on the efficacy estimand. 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
• Mazdutide in Chinese adults with overweight or obesity (GLORY-1) — New England Journal of Medicine

VK2735 —17.8% mean weight change21 wk · obesity · raw change

StagePhase 3

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

Maker

Routeinjection (weekly; every-other-week and monthly maintenance dosing tested); oral (daily) in development

Indicationsinvestigating obesity, type 2 diabetes

Efficacy17.8% at 21 wks on 17.5 mg weekly (raw change, n=118) in the VK2735-102 maintenance study; 14.7% at 13 wks in Phase 2 VENTURE; oral VK2735 ~12.2% at 13 wks (VENTURE-Oral) source

Key trials

• VK2735-102 maintenance study (obesity) — ~180 adults with obesity, 21 weeks of weekly injections, then 12 weeks on less frequent maintenance doses or placebo. Weight loss at week 21 was 16.3–18.7% across doses vs 0.1% on placebo. After switching, every-other-week dosing kept 90% of that loss and monthly dosing kept 85% at week 33, vs 61% for people switched to placebo. Side effects during maintenance ran at or below placebo. Weight was an exploratory endpoint (the study's stated goals were safety, tolerability and drug levels), each maintenance arm had only 10–16 people, and the results are a company press release, not peer-reviewed. A ClinicalTrials.gov entry for a study of this design (NCT07838740) was first posted on 24 September 2026, two days after these results. source
• VK2735 maintenance study, Part 2 (oral and injectable maintenance) (obesity) — About 195 adults with obesity (BMI 30 or higher) and no other health conditions, randomised, double-blind and placebo-controlled. Everyone gets weekly injections of VK2735 or placebo for 21 weeks, then switches to one of several maintenance options through week 33: a daily tablet, a weekly tablet, a monthly injection, an injection every other week, or placebo. The stated goals are safety, tolerability and drug levels; weight change is an exploratory endpoint, as it was in Part 1. Viking expects results in 2027. A ClinicalTrials.gov entry with these arms (NCT07838740, Phase 1) lists an estimated 270 participants and an estimated primary completion date of May 2027. source

aleniglipron (GSBR-1290) —16.3% mean weight change44 wk · obesity · placebo-adjusted

StagePhase 3 (enrolling)

TargetsGLP-1 receptor agonist (oral, non-peptide small molecule)

Maker

Routeoral (daily)

Indicationsinvestigating obesity, type 2 diabetes

Efficacy16.3% placebo-adjusted at 44 wks on 180 mg and 16.0% on 240 mg — the two higher doses ACCESS II was built to test. Absolute change from baseline was -15.3% at 180 mg and -15.0% at 240 mg; the gap is because placebo GAINED 1.1%. The 120 mg reference arm was -14.7% placebo-adjusted. A separate earlier trial, ACCESS, gave 11.3% at 36 wks. A 72-week open-label extension of ACCESS (Sept 2026, no placebo comparator after week 36) followed participants originally randomized to 45 mg, 90 mg and 120 mg who all escalated up to 180 mg by ~week 60: they reached 11.6%, 14.4% and 16.2% weight loss respectively, with no plateau in the two top cohorts. More than a third of the 90 mg and 120 mg cohorts lost over 20% of body weight (mean absolute loss 35.9 and 40.5 lbs), and fewer than 5% discontinued for adverse events across the OLE. source

Key trials

• ACCESS (Phase 2b) (Ph 2, obesity) — NCT06693843, n=230 randomised, 36 wks. Source of the 11.3% figure; published in Nature Medicine. source
• ACCESS II (Phase 2b, higher doses) (Ph 2, obesity) — NCT06703021, 44 wks, built to test 180 mg and 240 mg: -16.3% and -16.0% placebo-adjusted, with the 120 mg reference arm at -14.7%. source
• ACCESS OLE (72-wk open-label extension) (Ph 2, obesity) — Prespecified 36-week extension of ACCESS (NCT06693843) to 72 wks total; 87% of eligible ACCESS completers enrolled. Original 45/90/120 mg arms, escalated to 180 mg by ~week 60, reached 11.6%/14.4%/16.2% weight loss with no plateau in the top two. Placebo crossovers started at a lower 2.5 mg dose (vs. 5 mg in the original trial) and showed improved GI tolerability. <5% discontinued for adverse events; no drug-induced liver injury. source

Papers

• Aleniglipron (GSBR-1290) in adults with obesity: the ACCESS phase 2b trial — Nature Medicine

petrelintide —10.7% mean weight change42 wk · obesity · raw change

StagePhase 3 (started)

Targetsamylin long-acting amylin analog

Maker

Routeinjection (weekly)

Indicationsinvestigating obesity

EfficacyUp to 10.7% mean weight loss at 42 wks vs 1.7% placebo (ZUPREME-1 Phase 2, amylin analog). On 22 Sep 2026 Zealand and Roche announced the start of the registrational Phase 3 ZUPREME program: three placebo-controlled trials, about 7,000 people, primary endpoint weight change at week 64. source

Key trials

• ZUPREME-2 (NCT06926842) (Ph 2, overweight or obesity with type 2 diabetes) — Topline from Zealand's 7 Oct 2026 announcement; full results are promised for a scientific conference. 220 US adults with overweight or obesity and type 2 diabetes (mean BMI 36.3, mean HbA1c 8.0%) on metformin with or without an SGLT2 inhibitor got one of three weekly doses or placebo for 28 weeks, including up to 16 weeks of dose escalation. Mean weight loss was 7.4% to 9.2% across the three doses vs 2.0% on placebo (efficacy estimand; the company says the treatment-regimen estimand was largely consistent and gives no figure). HbA1c fell by up to 0.65% and rose 0.23% on placebo, a placebo-adjusted reduction of 0.61% to 0.88%. 1.9% on petrelintide stopped treatment for gastrointestinal side effects vs 1.7% on placebo. Doses and per-arm numbers were not given. source
• ZUPREME-3, -4 and -5 (Phase 3a programme) (Ph 3, obesity / overweight, including type 2 diabetes and established cardiovascular disease) — Announced 22 Sep 2026, run with Roche. ZUPREME-3: about 3,900 people with obesity, or overweight plus at least one weight-related condition, without type 2 diabetes. ZUPREME-4: about 600 people with type 2 diabetes. Both have 12 weeks of dose escalation, treatment to week 64, then an optional open-label extension in which everyone is offered petrelintide. ZUPREME-5: about 2,500 people with established cardiovascular disease; same week-64 primary assessment, then it continues for up to 3 years in total. Primary endpoint in all three: % change in body weight at week 64 vs placebo. None of the three was listed on ClinicalTrials.gov as of 23 Sep 2026, and no readout date has been given. source

enicepatide (CT-388 / RO7795068) —22.5% mean weight change48 wk · obesity · efficacy estimand · placebo-adjusted

StagePhase 3

TargetsGIPGLP-1 dual agonist (cAMP signal-biased, minimal beta-arrestin recruitment)

Maker

Routeinjection (weekly)

Indicationsinvestigating obesity, type 2 diabetes

Efficacy22.5% placebo-adjusted at 48 wks (efficacy estimand; 18.3% treatment-regimen) in Phase 2 CT388-103 at 24 mg, no plateau; 26.1% lost ≥30% source

Key trials

• CT388-103 (Ph 2, obesity / overweight without T2D (dose-finding)) — n=469, 48 wks, top dose 24 mg weekly: 22.5% placebo-adjusted weight loss (efficacy estimand; 18.3% treatment-regimen), no plateau. Responders at 24 mg: 95.7% ≥5%, 87% ≥10%, 47.8% ≥20%, 26.1% ≥30%; 54% resolved obesity (BMI <30) vs 13% placebo; 73% of pre-diabetic participants reached normoglycemia vs 7.5% placebo. Discontinuation for AEs 5.9% vs 1.3% placebo. Full data at ADA 2026. source
• CT388-104 (Ph 2, obesity / overweight + type 2 diabetes) — n=447, randomized double-blind placebo-controlled, 48 wks, in adults with T2D and overweight/obesity. Top dose 24 mg weekly: mean HbA1c reduction 2.65% (from baseline 8.1%; 4.13% in those with baseline HbA1c >8.5%), 90% reached HbA1c ≤6.5%, 62% reached normoglycemia (<5.7%). Mean weight loss 15.5% at 48 wks, no plateau. Discontinuation for AEs 2.0% vs 0.0% placebo; mild-to-moderate GI AEs, no new safety signals. ⚠️ Roche's release does not label the 15.5% placebo-adjusted or give an estimand (unlike CT388-103's 22.5%) — treat as raw mean change in a sicker (T2D) population, not a new headline number. source
• Phase 3 program (obesity) (Ph 3, obesity) — Two Phase 3 obesity trials recruiting since March 2026 (NCT07351045, NCT07351058). source
• Phase 3 (China) (Ph 3, obesity) — NCT07670416, recruiting since 3 Jul 2026 — a third Phase 3 alongside NCT07351045 and NCT07351058. source

eloralintide —20.1% mean weight change48 wk · obesity · raw change

StagePhase 3

Targetsamylin selective amylin receptor agonist

Maker

Routeinjection (weekly)

Indicationsinvestigating obesity, type 2 diabetes, obstructive sleep apnea, knee osteoarthritis

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

Beyond weight loss

• ✓ Diabetes (A1c): In type 2 diabetes, eloralintide alone lowered HbA1c by 1.1 to 1.4 points; combined with tirzepatide, by up to 2.9 points against 2.4 on tirzepatide 15 mg alone (48 weeks, efficacy estimand) (EloraTZP Phase 2b (NCT06603571), Lilly topline, EASD 2026 · 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
• EloraTZP Phase 2b with tirzepatide (NCT06603571) (Ph 2, obesity/overweight with type 2 diabetes) — 367 adults with obesity or overweight and type 2 diabetes, split evenly across ten groups (about 37 each), 48 weeks; eloralintide and tirzepatide given as two separate weekly injections. Efficacy estimand (people who stayed on treatment): eloralintide 9 mg + tirzepatide 15 mg -23.3% weight and -2.9 points HbA1c, against -14.8% and -2.4 on tirzepatide 15 mg alone and -3.0% and -0.3 on placebo. Eloralintide alone: -8.2% (3 mg), -12.3% (6 mg), -11.1% (9 mg). Only the comparison with placebo was the primary endpoint; the comparison with tirzepatide alone was secondary. Stomach side effects were more common on the combinations, and 10.8% to 27.0% of people on a combination stopped because of side effects, against 2.9% on tirzepatide alone and 16.7% on placebo. source
• ENLIGHTEN (Phase 3 programme) (Ph 3, obesity, type 2 diabetes, OSA, knee osteoarthritis) — Five trials recruiting: ENLIGHTEN-1 NCT07321886, -2 NCT07282600, -3 NCT07369011 (obstructive sleep apnea), -4 NCT07353931 (knee osteoarthritis) and -6 NCT07392190. source
• AMPLIFY (Phase 3 programme, EloraTZP) (Ph 3, obesity/overweight, with and without type 2 diabetes) — Lilly's slides for analysts at EASD (30 September 2026) name three planned Phase 3 trials of EloraTZP as a single co-formulated injection with a revised dose-escalation schedule, and say the programme starts in 2026. AMPLIFY-1: EloraTZP against tirzepatide alone and eloralintide alone in people with a BMI above 35 and no type 2 diabetes. AMPLIFY-2: EloraTZP against tirzepatide in people with type 2 diabetes. AMPLIFY-3: the same three-way comparison as AMPLIFY-1 in people with a BMI of 27 to under 35 and no type 2 diabetes. The slide gives no sizes, doses or endpoints, and none of the three was on ClinicalTrials.gov as of 7 October 2026. 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

MET-233i (renamed PF-08653945) —8.4% mean weight change5 wk · obesity · placebo-adjusted

StagePhase 2

Targetsamylin ultra-long-acting amylin analog (monthly)

Maker

Routeinjection (monthly)

Indicationsinvestigating obesity

EfficacyUp to 8.4% placebo-subtracted after five WEEKLY 1.2 mg doses at day 36 (Phase 1, 80 adults). The ~19-day half-life is what supports a future monthly product — it is not how this result was produced. Pfizer renamed the molecule PF-08653945 after acquiring Metsera; its GLP-1 partner MET-097i is now berobenatide (PF-08653944). source

Key trials

• SOLIS-1 (Phase 2b) (Ph 2, obesity) — NCT07575932, n=872, recruiting since 11 May 2026, testing PF-08653945 with PF-08653944 (berobenatide). source

berobenatide (MET-097i / PF-08653944) —14.1% mean weight change28 wk · obesity · placebo-adjusted

StagePhase 3

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 on weekly 1.2 mg (VESPER-1) and 12.3% placebo-adjusted monthly (VESPER-3). A separate 32-week extension reached ~15.9% on the highest weekly dose — that one is an absolute figure, not placebo-adjusted, so it is not the same measure as the two above. 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
• VESPER-4 + Phase 3 programme (Ph 3, obesity) — VESPER-4 (NCT07311850, n=3,501) has been recruiting since 19 Dec 2025, with NCT07400653 (n=999, Feb 2026) and NCT07595549 (n=954, Jun 2026) following. source
• Q2 2026 earnings call (company statement, not a trial) (Ph 3, obesity) — Pfizer CSO Chris Boshoff said an internal analysis "suggests berobenatide can deliver weight loss comparable to tirzepatide and potentially better than semaglutide." This is a sponsor cross-trial comparison, not a head-to-head trial, and no head-to-head against either drug has been run. Treat as a company claim until VESPER-4 and the wider Phase 3 programme report. source

ribupatide (KAI-9531 / HRS9531) —23.6% mean weight change36 wk · obesity · efficacy estimand · raw change

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
• KaiNETIC-2 and further Phase 3s (Ph 3, obesity, knee osteoarthritis) — KaiNETIC-2 (NCT07284901, n=1,156) recruiting since 12 Jan 2026, plus a Phase 3 in obesity with knee osteoarthritis (NCT07709910, n=382) from Jul 2026. source

efpeglenatide —9.8% mean weight change40 wk · obesity, no T2D · raw change

StageFiled · Korea

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.

elecoglipron (AZD5004 / ECC5004) —10.5% mean weight change26 wk · obesity, no T2D · raw change

StagePhase 3

TargetsGLP-1 receptor agonist (oral, small molecule)

Maker

Routeoral (daily, no food/water restriction)

Indicationsinvestigating obesity, type 2 diabetes

Efficacy10.5% mean weight loss at 26 wks and 11.8% at 36 wks on 75 mg (VISTA Phase 2b, n=310, obesity without diabetes) vs 0.6% placebo. In type 2 diabetes (SOLSTICE, n=406) HbA1c fell 1.88 points on the 75 mg every-two-week escalation arm vs 0.15 on placebo. SOLSTICE also included an oral semaglutide 14 mg arm that fell 1.28 points — but that arm was open-label and exploratory, and the trial was not powered to compare the two drugs, so it is not a head-to-head result. source

Beyond weight loss

• · Everything else: Early-stage oral GLP-1; CV/OSA/other effects untested. The orforglipron competitor in the oral-GLP-1 race. (no data yet)

Access & priceNot yet available

Key trials

• VISTA (Phase 2b, obesity) (Ph 2, obesity without diabetes) — n=310, 36 wks. 75 mg weekly titration: -10.5% at wk 26 vs -0.6% placebo, -11.8% at wk 36; 5 mg -2.6%. 40.4-88.8% lost 5% or more vs 15.6% on placebo. source
• SOLSTICE (Phase 2b, type 2 diabetes) (Ph 2, type 2 diabetes) — n=406. HbA1c -1.88 on the 75 mg every-two-week escalation arm vs -0.15 placebo; weight down to -7.7%. An oral semaglutide 14 mg arm fell -1.28, but it was open-label and exploratory and the trial was not powered for that comparison. source
• Embold + Eluminate (Phase 3 programme) (Ph 3, obesity / type 2 diabetes) — Six Phase 3 trials registered, five already recruiting: Embold master protocol NCT07667803 (n=4,500, started 29 Jun 2026), Eluminate-4 NCT07662135 (n=900), plus NCT07662109 (n=2,000), NCT07662213 (n=1,200) and NCT07662044 (n=800), all from 6 Jul 2026. The sixth, Eluminate-3 (NCT07664553), is registered but not yet recruiting. source

Papers

• Elecoglipron in adults with obesity or overweight (VISTA) — The Lancet
• Elecoglipron in adults with type 2 diabetes (SOLSTICE) — The Lancet

HRS-7535 / KAI-7535 (oral) —11.1% mean weight change50 wk · obesity · efficacy estimand · raw change

StagePhase 3

TargetsGLP-1 oral small-molecule GLP-1 receptor agonist

Maker

Routeoral (once daily)

Indicationsinvestigating obesity, type 2 diabetes

Efficacy11.1% weight loss at 50 wks (China Phase 3 HARBOR-1, 180 mg; 10.9% at 44 wks vs 2.5% placebo, efficacy estimand). Steep GI: vomiting up to 68.6%, nausea ~70%. source

Key trials

• HARBOR-1 (China Phase 3, obesity) (Ph 3, obesity) — 180 mg: -10.9% at 44 wks / -11.1% at 50 wks; 120 mg: -9.5%; placebo -2.5% (efficacy estimand; treatment-policy -9.8%/-8.0% vs -2.4%). Nausea ~70%, vomiting 66.7-68.6%, diarrhea ~36% (vs placebo 16.2/4.5/15.3%); discontinuation 3.1-4.1% vs 2.7% placebo; no liver safety signal. source
• OUTSTAND-2 (China Phase 3, type 2 diabetes) (Ph 3, type 2 diabetes) — HbA1c -1.58%/-1.50%/-1.68% at 32 wks (30/60/90 mg) vs -1.28% dapagliflozin 10 mg; no liver signal, no Grade 3 hypoglycemia. source
• Global Phase 2 (obesity) (Ph 2, obesity) — Initiated Apr 2026 with a lower 15 mg start dose and gentler titration to blunt GI intolerability; data expected 2027. This is the Western-relevant program (the Phase 3 above is China-only). source

BI 3034701 —

StagePhase 2

TargetsGLP-1GIPNPY2 triple receptor agonist

Maker

Routeinjection (long-acting peptide; dosing interval not disclosed)

Indicationsinvestigating obesity, overweight

EfficacyNo efficacy data disclosed — none at all. Phase 1 (125 participants, completed Oct 2025) yielded only a "generally favorable safety and tolerability profile." No weight-loss figures, preclinical or clinical, have been released. source

Beyond weight loss

• · The NPY2 pathway itself: First multi-receptor obesity agonist to include NPY2 (neuropeptide Y receptor type 2). NPY2 acts as a brake on NPY hunger signaling and slows gastric emptying — in theory blunting the body's defense against fat loss. But every standalone NPY2 agonist so far has failed: BI's own BI 1820237 was discontinued after GI adverse events, and Novo's PYY1875 (NN9748) died in Phase 2 because it "was not well tolerated." The GIP arm here is likely the tolerability play, since GIP is anti-emetic and both GLP-1 and NPY2 drive nausea and vomiting. (mechanistic rationale only; no human efficacy data for this molecule · source)

Access & priceNot yet available

Key trials

• NCT06352437 (Phase 1 SAD/MAD) (Ph 1, healthy adults + overweight/obesity) — 125 participants; started 10 Jun 2024, completed 7 Oct 2025. BI cites a "generally favorable safety and tolerability profile" as the basis for advancing. No results posted, no efficacy disclosed. source
• NCT07662122 (Phase 2) (Ph 2, obesity / overweight) — 300 participants; dose-finding weight-loss study. Started 30 Jun 2026, announced 16 Jul 2026. Primary completion 4 Aug 2027 — that is when the first real efficacy read arrives. source
• NCT07693231 + NCT07708493 (Phase 1 support) (Ph 1, Japanese cohort tolerability; pharmacokinetics) — 48-participant Japanese SAD/MAD and an 8-participant PK study, both starting late Jul 2026. Standard groundwork for a global program. source

Watch list (earlier stage)

Molecule	Maker	Targets	Stage	Mean weight change	What's next
pemvidutide —		glucagonGLP-1	Phase 2 complete	15.6%48 wk · obesity · raw change	PERFORMA Phase 3 planned; no Phase 3 registered yet (2026-H2)
ABBV-295 (GUB014295) —		amylin	Phase 1	7.75%12 wk · mean BMI under 30, 88% men · raw change	Advancing toward Phase 2 (2026)
ACCG-2671 —		amylin	Phase 1	3.3%Day 24 · healthy adults without obesity · single 10 mg dose, raw change	Phase 1/2a MAD topline data (12-week multiple ascending dose portion, adults with obesity, incl. a GLP-1-combination cohort) (2027-H1)
AZD6234 —		amylin	Phase 2 complete	—	AZD9550 + AZD6234 combination readout (2026-H2)
HM17321 (LA-UCN2) —	Hanmi Pharmaceutical / Genentech (Roche)	UCN2	Phase 1	—	Phase 1 completion (NCT07219589); Genentech assumes development from Phase 2
HRS-1596 —	Hengrui Pharma / Novo Nordisk (rights outside mainland China, Hong Kong, Macao and Taiwan)	GIPGLP-1	Phase 1 (China approved to initiate; no patient dosed yet)	—	First Phase 1 dosing in China (approved but not yet started); deal expected to close Q4 2026, subject to Hart-Scott-Rodino antitrust clearance
PF-08642534 (YP05002) —	Pfizer (licensed from YaoPharma)	GLP-1	Pre-Phase 3	—	First efficacy data (TBD)

These percentages are not a league table. Each is the highest-dose mean result at the approved (or trial) obesity dose, but the conditions differ — read the small print under each number. Trials vary in length (5 to 80 weeks) and in population (with or without type 2 diabetes), and the result is calculated in more than one way. Raw change is the change from baseline; placebo-adjusted subtracts the placebo group. Beyond that, sponsors report an idealised estimate of what happens if you stay on the drug — Lilly calls it the efficacy estimand, Novo the trial-product estimand — and a second figure that includes people who stopped or switched, labelled treatment-regimen or treatment-policy depending on the trial. The first will usually read higher than the second. Those two labels are not strictly interchangeable; each trial defines its own, so treat them as a family rather than one thing. Two drugs are only comparable when duration, population and calculation method all match. Diabetes brands and lower doses come in below the figure shown; see each drug's card for the per-product breakdown.

pemvidutide —15.6% mean weight change48 wk · obesity · raw change

StagePhase 2 complete

TargetsglucagonGLP-1 dual agonist

Maker

Routeinjection

Indicationsinvestigating obesity, MASH, alcohol use disorder

Efficacy15.6% mean weight loss at 48 wks (Phase 2 MOMENTUM, 2.4 mg) source

Beyond weight loss

• ✓ MASH / liver: FDA Breakthrough Therapy Designation granted for MASH. The IMPACT Phase 2b 48-week data showed ELF and liver-stiffness improvements versus placebo, and among patients with elevated baseline values, the 1.8 mg dose cut triglycerides 23.7% and total cholesterol 15.4%. (Phase 2b IMPACT, EASL 2026 · source)

Key trials

• MOMENTUM (Phase 2, obesity) (Ph 2, obesity) — 15.6% mean weight loss at 48 wks on 2.4 mg — still the newest obesity figure. source
• IMPACT (Phase 2b, MASH) (Ph 2, MASH) — 48-week data at EASL 2026: ELF and liver-stiffness improvements vs placebo. Among patients with elevated baseline values, 1.8 mg cut triglycerides 23.7% and total cholesterol 15.4% — those lipid figures are a subgroup, not the whole trial. FDA Breakthrough Therapy Designation granted. source
• RECLAIM (Phase 2, alcohol use disorder) (Ph 2, alcohol use disorder) — NCT06987513, n=100. source

ACCG-2671 —3.3% mean weight changeDay 24 · healthy adults without obesity · single 10 mg dose, raw change

StagePhase 1

Targetsamylin oral small molecule dual amylin and calcitonin receptor agonist (DACRA); non-peptide

Maker

Routeoral

Indicationsinvestigating obesity

EfficacyPhase 1 single ascending dose (SAD) data only, in 31 healthy adults without obesity (no efficacy claim in an obesity population yet). A single 10 mg dose (n=6) produced 3.3% mean body weight loss by Day 24, alongside a ~60% drop in CTX-1 (a bone-resorption biomarker) — evidence of target engagement, not a powered efficacy result. Terminal half-life ran ~6 days, supporting potential once-weekly dosing. No serious adverse events or liver-enzyme elevations; nausea/vomiting emerged at the 5 mg (4/5 and 3/5 participants) and 10 mg (6/6) doses. Structure calls it the first reported clinical data for an oral small-molecule amylin receptor agonist. source

Key trials

• Phase 1/2a SAD/MAD (Ph 1, obesity) — SAD portion (complete): 31 healthy adults without obesity, single doses of 1/2/5/10 mg vs. placebo. MAD portion (dosing began Sept 2026): 5 cohorts of adults with obesity, 84 days, daily and weekly regimens, including a cohort combined with a stable dose of an injectable GLP-1 receptor agonist. Topline MAD data expected 1H 2027. source

ABBV-295 (GUB014295) —7.75% mean weight change12 wk · mean BMI under 30, 88% men · raw change

StagePhase 1

Targetsamylin long-acting amylin analog

Maker

Routeinjection (weekly, every-other-week and monthly in trials)

Indicationsinvestigating obesity

Efficacy7.75% to 9.79% weight loss at 12 wks vs -0.26% placebo (Phase 1 multiple-ascending-dose, 76 adults) — but read the population before comparing it to anything else here: mean BMI was under 30, so these were not adults with obesity, and 88.3% of participants were men. Well tolerated, no serious adverse events. AbbVie's first obesity asset. source

AZD6234 —

StagePhase 2 complete

Targetsamylin long-acting amylin (AMY3R) agonist

Maker

Routeinjection (weekly)

Indicationsinvestigating obesity

EfficacyPhase 2 complete, no efficacy data released. APRICUS (NCT06595238, n=262) reached primary completion 3 Dec 2025 and ASCEND (NCT06862791, n=377) on 11 May 2026, and neither has posted results. AstraZeneca now points the AZD9550 + AZD6234 combination readout to H2 2026. source

Key trials

• APRICUS (Ph 2, obesity) — NCT06595238, n=262. Actual primary completion 3 Dec 2025. No results posted. source
• ASCEND (AZD9550 + AZD6234 combination) (Ph 2, obesity) — NCT06862791, n=377. Actual primary completion 11 May 2026. No results posted. source
• ARAY (Ph 2, obesity) — NCT06851858. source