GLP-1 Clinical Trials Tracker 2025–2026: The Complete Pipeline
SURMOUNT-5, ACHIEVE-1, ATTAIN-1, REDEFINE 1, TRIUMPH-4, MARITIME, EVOKE, SOUL, SUMMIT — every major Phase 3 GLP-1, dual-agonist, and triple-agonist trial program, with sponsors, results, status, and what to watch in the rest of 2026.
Between January 2025 and April 2026, the GLP-1 clinical trial landscape produced more pivotal Phase 3 results than the entire decade preceding it. Tirzepatide and semaglutide finally went head-to-head in a direct comparison. The first oral non-peptide GLP-1, orforglipron, completed multiple Phase 3 readouts. A monthly injection moved into Phase 3. A triple agonist crossed the 28% weight loss threshold. And one of the most-watched trials in the field — testing whether semaglutide could slow Alzheimer's disease — returned a clear negative result.
This is a complete tracker of the major Phase 3 trial programs across the GLP-1, dual-agonist, and triple-agonist drug class. It's organized by trial program rather than by drug, so each section gives you the trial design, the result, the status, and what comes next. Sources are listed at the end, and trial codes (NCT identifiers) are included so anything here can be verified directly on ClinicalTrials.gov.
Programs Covered
- SURMOUNT — Tirzepatide (Lilly)
- ACHIEVE & ATTAIN — Orforglipron (Lilly)
- REDEFINE — CagriSema (Novo Nordisk)
- TRIUMPH — Retatrutide (Lilly)
- MARITIME — MariTide (Amgen)
- EVOKE — Semaglutide for Alzheimer's (Novo Nordisk)
- SOUL — Semaglutide CV Outcomes (Novo Nordisk)
- SUMMIT — Tirzepatide for HFpEF (Lilly)
- STEP — Foundational Semaglutide Trials
- Beyond GLP-1: Survodutide, Pemvidutide, Amycretin
- What's Coming Next in 2026
SURMOUNT Program — Tirzepatide (Zepbound)
Lilly's SURMOUNT program established tirzepatide as the highest-efficacy approved GLP-1-class medication for weight management. The program now spans seven trials covering chronic weight management, type 2 diabetes (under the SURPASS umbrella), obstructive sleep apnea, heart failure with preserved ejection fraction, MASH, and a head-to-head comparison with semaglutide.
The pivotal weight management trial. Tirzepatide delivered up to ~22.5% mean weight loss at the highest dose at 72 weeks, supporting Zepbound's FDA approval in November 2023.
The first head-to-head trial of tirzepatide versus semaglutide in adults with obesity (without diabetes). Tirzepatide produced a mean weight reduction of 20.2% compared with 13.7% for semaglutide at 72 weeks — a 47% greater relative weight loss using the treatment-regimen estimand.
Key secondary endpoints: 31.6% of participants on tirzepatide achieved at least 25% body weight loss, compared with 16.1% on semaglutide. Waist circumference reduction was −18.4 cm with tirzepatide vs −13.0 cm with semaglutide. Tirzepatide was also superior on systolic and diastolic blood pressure, HbA1c, fasting insulin, triglycerides, and HDL.
Gastrointestinal adverse events leading to discontinuation occurred in 5.6% of semaglutide patients vs 2.7% of tirzepatide patients. The trial was open-label and funded by Eli Lilly — both factors that warrant transparency, but neither invalidates a peer-reviewed NEJM publication.
Demonstrated tirzepatide's effect on obstructive sleep apnea severity, leading to FDA approval of Zepbound for moderate-to-severe OSA in adults with obesity in December 2024.
ACHIEVE & ATTAIN — Orforglipron (Lilly's Oral GLP-1)
Orforglipron is the first oral, small-molecule, non-peptide GLP-1 receptor agonist to complete Phase 3 trials. Unlike Rybelsus (oral semaglutide, which requires an empty stomach and a 30-minute waiting window), orforglipron has no food or water restrictions — a meaningful change in real-world usability if approved. Lilly licensed the molecule from Chugai Pharmaceutical in 2018.
Lilly is running two parallel Phase 3 programs: ACHIEVE for type 2 diabetes (five global registration trials, >6,000 enrolled) and ATTAIN for obesity. Lilly has stated it plans to submit orforglipron for obesity by end of 2025 and for type 2 diabetes in 2026.
The first Phase 3 readout for orforglipron. Lowered HbA1c by an average of 1.3% to 1.6% from a baseline of 8.0%. Highest dose (36 mg) reduced weight by an average of 7.9% (~16 lbs). Safety profile consistent with injectable GLP-1s, with mild-to-moderate gastrointestinal adverse events most common. 94.1% of participants completed the trial.
Head-to-head against the SGLT-2 inhibitor dapagliflozin in patients inadequately controlled on metformin. All three orforglipron doses (3 mg, 12 mg, 36 mg) met primary and key secondary endpoints.
Head-to-head versus oral semaglutide in patients inadequately controlled on metformin. Orforglipron delivered superior blood sugar control and weight loss. Detailed results published in The Lancet.
Tested orforglipron as an add-on to titrated insulin glargine, with or without metformin and/or SGLT-2 inhibitors. Met primary and key secondary endpoints across all three doses.
The last of the five Phase 3 ACHIEVE trials. Topline results expected in the first quarter of 2026, completing the orforglipron T2D registration package.
Highest dose (36 mg) produced 12.4% (~27.3 lbs) weight loss versus 0.9% with placebo using the efficacy estimand. Treatment discontinuation rates ranged from 21.9% (6 mg) to 24.4% (36 mg) versus 29.9% with placebo — meaning fewer people stopped on the active drug. Detailed results presented at EASD 2025.
The 12.4% figure was viewed as somewhat below the most optimistic expectations for an oral GLP-1, but represents a meaningful weight loss in a once-daily pill format with no food/water restrictions.
Highest dose produced 10.5% (~22.9 lbs) weight loss with HbA1c reduction of 1.3% to 1.8% from a baseline of 8.1%. Patients with obesity plus T2D typically have more difficulty losing weight, making this a meaningful result.
REDEFINE Program — CagriSema (Novo Nordisk)
CagriSema is Novo Nordisk's fixed-dose combination of cagrilintide (a long-acting amylin analog) plus semaglutide, both at 2.4 mg, administered subcutaneously once weekly. The combination is designed to engage two complementary appetite-regulating pathways simultaneously.
Met its primary endpoint with 22.7% mean weight loss at 68 weeks (treatment-regimen estimand) — but fell short of the ≥25% threshold the company had previously signaled in investor communications, and Novo's stock dropped on the result. 40.4% of participants achieved at least 25% weight loss when accounting for full treatment adherence. Notably, only 57.3% of patients reached the highest CagriSema dose.
The T2D companion trial. Met primary endpoints with significant weight loss versus placebo. Together with REDEFINE 1, this trial supported Novo Nordisk's NDA submission to the FDA on December 18, 2025.
The cardiovascular outcomes trial for CagriSema. Designed to demonstrate macrovascular benefit beyond weight loss alone.
Designed to explore the longer-term weight loss potential of CagriSema 2.4/2.4 mg with extended duration and protocol changes addressing the dose-titration issues seen in REDEFINE 1.
TRIUMPH Program — Retatrutide (Lilly's Triple Agonist)
Retatrutide is a first-in-class once-weekly triple hormone receptor agonist — a single molecule that activates GIP, GLP-1, and glucagon receptors. The addition of glucagon agonism is designed to increase energy expenditure on top of the appetite suppression that drives the GLP-1 and GIP effects. Phase 2 data published in 2023 hinted at the highest weight loss numbers ever recorded for an obesity drug; the Phase 3 TRIUMPH program is now confirming and extending those results across multiple indications.
The TRIUMPH program has enrolled more than 5,800 participants across studies in obesity, type 2 diabetes, knee osteoarthritis, obstructive sleep apnea, chronic low back pain, cardiovascular and renal outcomes, and MASH.
The first successful Phase 3 readout for retatrutide. The 12 mg dose produced an average 28.7% weight loss at 68 weeks (an average of 71.2 lbs lost), with a placebo-adjusted reduction of 26.6%. WOMAC pain scores for knee osteoarthritis improved by as much as 75.8%.
The trial tested only the two highest doses (9 mg and 12 mg). Additional TRIUMPH results, including a maintenance 4 mg dose, are expected throughout 2026. Lilly stock topped $1,000/share for the first time in pre-market trading on the readout.
The full TRIUMPH program covers chronic weight management, T2D, OSA, chronic low back pain, cardiovascular and renal outcomes, and MASH. Doses tested across the program: 2 mg, 4 mg, 6 mg, 9 mg, and 12 mg. Analysts have suggested TRIUMPH-1 (the 80-week obesity study) could potentially exceed 30% weight loss given its longer duration.
MARITIME Program — MariTide (Amgen's Monthly Injection)
MariTide (maridebart cafraglutide, formerly AMG 133) takes a fundamentally different approach from the rest of the field. It's an antibody-peptide conjugate that combines GLP-1 receptor agonism with GIP receptor antagonism — the opposite of tirzepatide's GIP agonism. The antibody scaffold gives it a 21-day half-life, enabling once-monthly subcutaneous dosing instead of weekly. If successful, MariTide would be the first monthly injectable obesity medication.
Demonstrated up to ~20% mean weight loss in adults with obesity without T2D, and up to ~17% in adults with both obesity and T2D, compared with 2.6% in placebo. Sustained weight loss without a 52-week plateau. Cardiometabolic risk factors improved. Safety profile consistent with the GLP-1 class — mostly mild-to-moderate gastrointestinal events.
The two pivotal Phase 3 weight management studies. Additional Phase 3 trials in atherosclerotic cardiovascular disease, heart failure, kidney disease, and obstructive sleep apnea are also planned or initiated. Amgen has not yet provided expected approval timing, but industry analysts widely expect FDA decisions in the 2028–2030 range.
EVOKE & EVOKE+ — Semaglutide for Early Alzheimer's Disease
The EVOKE trials were the first major Phase 3 attempt to test whether a GLP-1 medication could slow the progression of Alzheimer's disease — a hypothesis grounded in real-world observational data, preclinical models, and post-hoc analyses from semaglutide's diabetes and obesity trials. The result was one of the most consequential negative readouts in the GLP-1 trial era.
Two parallel Phase 3 trials enrolling adults aged 55–85 with mild cognitive impairment or mild Alzheimer's disease dementia and confirmed amyloid positivity. Tested oral semaglutide (titrated to 14 mg daily) versus placebo on top of standard of care.
The trials did not confirm superiority of semaglutide over placebo on the primary endpoint — change in Clinical Dementia Rating–Sum of Boxes (CDR-SB) score from baseline. While AD-related biomarkers improved with semaglutide, this did not translate into a delay of clinical disease progression. Safety and tolerability were consistent with prior semaglutide trials. The 1-year extension period in both trials was discontinued based on the readout.
The EVOKE result is important context for the broader "GLP-1s as anti-aging drugs" narrative that took hold in 2024–2025. The biology connecting GLP-1 receptor activation to brain health is real, but so far translating that biology into a clinically meaningful reduction in Alzheimer's progression has not been demonstrated.
SOUL Trial — Semaglutide CV Outcomes in T2D + Established Disease
Tested oral semaglutide for cardiovascular outcomes in adults with type 2 diabetes plus established cardiovascular disease or chronic kidney disease. Met its primary endpoint with a statistically significant reduction in major adverse cardiovascular events (MACE), extending the CV benefit established by injectable semaglutide in SUSTAIN-6 to the oral formulation. Detailed results presented at the American College of Cardiology meetings.
SUMMIT — Tirzepatide for HFpEF + Obesity
Demonstrated that tirzepatide reduced the composite risk of cardiovascular death or worsening heart failure events and improved Kansas City Cardiomyopathy Questionnaire scores in patients with HFpEF and obesity. Adds heart failure to the growing list of indications where GLP-1-class drugs improve outcomes beyond weight loss alone.
STEP Program — The Foundational Semaglutide Weight Loss Trials
The STEP program (Semaglutide Treatment Effect in People with Obesity) generated the data that brought Wegovy to market in 2021 and shaped the framework now used to evaluate every GLP-1 weight management drug.
The pivotal trial that supported Wegovy's FDA approval for chronic weight management in June 2021.
The trial that established obesity as a chronic relapsing disease in the GLP-1 era. Patients who discontinued semaglutide regained roughly two-thirds of the weight they had lost by week 68 after stopping. This finding fundamentally shaped how clinicians frame GLP-1 therapy with patients: it is a long-term treatment for a chronic condition, not a temporary intervention.
Beyond GLP-1: Other Late-Stage Incretin Programs
The pipeline beyond the four major sponsors (Lilly, Novo, Amgen, Boehringer) is substantial. Several programs warrant tracking even though they are earlier-stage:
The SYNCHRONIZE Phase 3 program is testing survodutide for chronic weight management, MASH, and other indications. Phase 2 data showed weight loss in the high teens at the highest doses.
Phase 2 weight management and MASH trials reading out across 2024–2025.
An emerging Novo Nordisk program designed as a single-molecule GLP-1/amylin co-agonist. Early Phase 1 data generated significant attention; Phase 2 trials underway.
Lilly's amylin program, intended for both monotherapy and combination use with their GLP-1 portfolio.
Quick-Look Database
A condensed view of every trial covered above:
| Trial | Drug | Sponsor | Status | Key Result |
|---|---|---|---|---|
| SURMOUNT-5 | Tirzepatide vs Semaglutide | Lilly | Published NEJM 5/2025 | 20.2% vs 13.7% at 72 wks |
| SURMOUNT-OSA | Tirzepatide | Lilly | Approved 12/2024 | OSA severity ↓ |
| ACHIEVE-1 | Orforglipron | Lilly | Topline 4/2025 | HbA1c ↓1.3–1.6% |
| ACHIEVE-3 | Orforglipron vs oral sema | Lilly | Topline 9/2025 | Superior glycemic control |
| ACHIEVE-4 | Orforglipron | Lilly | Q1 2026 | Final ACHIEVE readout |
| ATTAIN-1 | Orforglipron | Lilly | Topline 8/2025 | 12.4% wt loss at 36 mg |
| ATTAIN-2 | Orforglipron | Lilly | Topline 8/2025 | 10.5% wt loss (T2D + obesity) |
| REDEFINE 1 | CagriSema | Novo Nordisk | Published NEJM 6/2025 | 22.7% wt loss at 68 wks |
| REDEFINE 2 | CagriSema | Novo Nordisk | ADA 2025 | Met endpoints (T2D) |
| TRIUMPH-4 | Retatrutide | Lilly | Topline 12/2025 | 28.7% wt loss at 12 mg |
| MariTide Ph2 | MariTide | Amgen | NEJM 6/2025 | ~20% wt loss, monthly |
| EVOKE / EVOKE+ | Oral semaglutide | Novo Nordisk | Topline 11/2025 | Did NOT slow AD progression |
| SOUL | Oral semaglutide | Novo Nordisk | 2025 | MACE reduction (T2D+CVD/CKD) |
| SUMMIT | Tirzepatide | Lilly | NEJM 11/2024 | HFpEF + obesity ↓ events |
| STEP 4 | Semaglutide | Novo Nordisk | JAMA 2021 | ~⅔ regain after stopping |
What's Coming in 2026
The next twelve months are likely to be the densest period of incretin trial readouts in the field's history:
- Seven additional TRIUMPH retatrutide readouts — including the longer 80-week obesity studies that may push weight loss above 30%, plus the dedicated T2D, OSA, low-back-pain, and cardiovascular/renal outcome trials.
- ACHIEVE-4 final readout — Q1 2026, completing the orforglipron T2D registration package and clearing the path for Lilly's regulatory submission.
- Orforglipron FDA decisions — obesity submission was filed by end of 2025; T2D submission planned for 2026.
- CagriSema FDA decision — NDA was submitted December 18, 2025. Standard review timeline puts a potential approval in late 2026.
- Additional MariTide Phase 3 reads — initial data from MARITIME-1 and -2 expected; full readouts likely later given the 2023 Phase 3 launch timing.
- SURPASS-CVOT — Lilly's long-running cardiovascular outcomes trial of tirzepatide vs dulaglutide, with results expected to clarify CV benefit specifically attributable to the dual-agonist mechanism.
- Survodutide Phase 3 SYNCHRONIZE readouts — Boehringer Ingelheim's GLP-1/glucagon dual agonist.
- Amycretin Phase 2 data — Novo Nordisk's GLP-1/amylin single-molecule program, both oral and injectable formulations.
Why This Matters for Patients
The pipeline behind currently-approved GLP-1s is the deepest it has ever been. To put the trajectory into perspective:
| Era | Best-in-Class Weight Loss | Drug |
|---|---|---|
| Pre-GLP-1 (orlistat era) | ~3–5% | Various oral agents |
| Liraglutide (2014) | ~5–8% | Saxenda |
| Semaglutide (2021) | ~13.7–14.9% | Wegovy (STEP 1, SURMOUNT-5) |
| Tirzepatide (2023) | ~20.2–22.5% | Zepbound (SURMOUNT-1, SURMOUNT-5) |
| CagriSema (Phase 3, 2025) | ~22.7% | CagriSema (REDEFINE 1) |
| Retatrutide (Phase 3, 2025) | ~28.7% | Retatrutide (TRIUMPH-4) |
The ceiling continues to move. Equally important, the field is diversifying along axes other than raw efficacy: oral options (orforglipron) for patients who can't or won't inject; monthly dosing (MariTide) for adherence; combination mechanisms (CagriSema, retatrutide, survodutide) testing whether biology can be hit from multiple angles simultaneously.
Trial weight loss numbers come from highly selected populations under controlled protocols. Real-world results for any GLP-1 medication tend to be lower than the trial figures, often by 30–50%, due to lower adherence, less aggressive titration, and broader patient populations. The relative ranking among drugs generally holds; the absolute numbers do not.
While the Pipeline Plays Out: Current Access
Most of the trials covered here describe drugs that are not yet approved or are approved for indications other than what most readers are searching for. While the next generation works through the regulatory process, current GLP-1 medications remain accessible through both brand-name channels and licensed telehealth providers.
Comprehensive GLP-1 weight loss program with full clinical intake and ongoing medical oversight. Currently licensed to prescribe across most U.S. states.
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Compounded semaglutide and tirzepatide programs with full medical consultation, prescription, and ongoing provider support.
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Direct care platform that prescribes FDA-approved brand-name GLP-1 medications. Book a consultation with a licensed clinician.
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Between SURMOUNT-5 confirming tirzepatide's superiority over semaglutide, ACHIEVE/ATTAIN proving an oral GLP-1 works at scale, REDEFINE getting CagriSema to NDA submission, TRIUMPH-4 pushing weight loss past 28%, and MariTide moving monthly dosing into Phase 3 — the field is producing more pivotal data per quarter than at any point in its history. Expect another seven to ten major readouts before the end of 2026.
Sources & References
- Aronne LJ, et al. Tirzepatide vs Semaglutide for Obesity Treatment: SURMOUNT-5. N Engl J Med. 2025. NCT05822830.
- Eli Lilly. Zepbound (tirzepatide) showed superior weight loss over Wegovy (semaglutide) in complete SURMOUNT-5 results. Press release, May 11, 2025. prnewswire.com
- Eli Lilly. Lilly's oral GLP-1, orforglipron, demonstrated statistically significant efficacy results and a safety profile consistent with injectable GLP-1 medicines in successful Phase 3 trial (ACHIEVE-1). Press release, April 17, 2025.
- Eli Lilly. Lilly's oral GLP-1, orforglipron, demonstrated superior glycemic control in two successful Phase 3 trials (ACHIEVE-2 and ACHIEVE-5). Press release, October 15, 2025.
- Eli Lilly. ACHIEVE-3 head-to-head with oral semaglutide. Press release, September 17, 2025.
- Eli Lilly. ATTAIN-1 topline results: orforglipron in adults with obesity. Press release, August 7, 2025.
- Eli Lilly. ATTAIN-2 topline results: orforglipron in obesity + T2D. Press release, August 26, 2025.
- Novo Nordisk. CagriSema demonstrates superior weight loss in adults with obesity in the REDEFINE 1 trial. Press release, December 20, 2024.
- Novo Nordisk. CagriSema 22.7% mean weight reduction in REDEFINE 1, published in NEJM. Press release, June 22, 2025.
- Novo Nordisk. Files for FDA approval of CagriSema. Press release, December 18, 2025.
- Eli Lilly. Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs in TRIUMPH-4. Press release, December 11, 2025. NCT05931367.
- Amgen. Results from Amgen's Phase 2 obesity study of monthly MariTide presented at ADA 2025. Press release, June 2025. NCT05669599.
- Novo Nordisk. evoke phase 3 trials did not demonstrate a statistically significant reduction in Alzheimer's disease progression. Press release, November 24, 2025. NCT04777396 / NCT04777409.
- Cummings J, et al. Efficacy and safety of oral semaglutide 14 mg in early-stage symptomatic Alzheimer's disease (evoke and evoke+). The Lancet. 2026.
- Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023.
- Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384:989-1002.
- Rubino D, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults with Overweight or Obesity (STEP 4). JAMA. 2021;325(14):1414-1425.
- ClinicalTrials.gov — primary source for trial design, enrollment, and status. clinicaltrials.gov
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