The GLP-1 Pipeline: What's Coming Next
Last updated: March 2026
Five next-generation weight loss drugs are racing toward approval — oral small molecules, dual GLP-1/amylin agonists, and dual GLP-1/glucagon compounds. Some could outperform Wegovy by 2027.
In Pipeline
Top Candidates
Approval
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The GLP-1 Revolution Is Just Getting Started
Semaglutide (Wegovy) and tirzepatide (Zepbound) changed obesity treatment — but the next wave of drugs could be even more powerful, more convenient, or both.
First true oral small-molecule GLP-1 agonist. Unlike peptide-based oral GLP-1s (Rybelsus), orforglipron doesn't require food timing restrictions — a potential game-changer for accessibility.
Combined GLP-1 + amylin agonist. Combines cagrilintide (long-acting amylin analog) with semaglutide. Targets both pathways for enhanced satiety and glucose control.
Dual GLP-1/glucagon agonist with Breakthrough Therapy designation for MASH. Direct liver fat clearance via glucagon — the strongest liver fat data of any GLP-1.
Liver-focused dual GLP-1/glucagon with balanced 1:1 ratio. Also being studied for alcohol use disorder (RECLAIM trial). Strong liver fat reduction.
First dual GLP-1/glucagon agonist approved anywhere — now approved in China (2025). GLORY-2 trial showed 20.1% weight loss. DREAMS-3 beat semaglutide head-to-head in type 2 diabetes.
Trial Updates: The Numbers Keep Moving
Published data from 2025–2026 trials across all five pipeline drugs. This is where the real picture gets interesting.
The ATTAIN trial program produced multiple published readouts across obesity and T2D populations:
- ▸ ATTAIN-1 (2025, NEJM): 12.4% weight loss at 72 weeks. 54.6% of participants lost ≥10%, 36% lost ≥15%.
- ▸ ATTAIN-2 (2025): 10.5% loss in T2D population — harder to treat than obesity-only. A1C reduction of 1.8 percentage points.
- ▸ ATTAIN-MAINTAIN (2026): Successfully maintained weight in patients switching from injectable GLP-1s to oral orforglipron — a significant practical finding.
- ▸ ACHIEVE-2/5 (2025–2026): An additional 2.1% A1C reduction when orforglipron was added on top of existing insulin therapy.
The REDEFINE trials showed cagrisema approaching bariatric surgery territory — and in one head-to-head, came close to tirzepatide:
- ▸ REDEFINE 1 (2025): 20.4% weight loss at 68 weeks across 3,417 participants — one of the largest obesity drug trials ever.
- ▸ REDEFINE 2 (2025): 15.7% loss in T2D — higher than semaglutide in comparable T2D populations.
- ▸ REDEFINE 4 (2026): Head-to-head vs tirzepatide at 84 weeks — cagrisema 23.0% vs tirzepatide 25.5%. Not a win, but competitive within striking distance of the current market leader.
- ▸ REDEFINE 11: Higher-dose cohort expected H1 2027. Could push numbers above 25%.
Phase 2 weight loss was 18.7% at 46 weeks (54.7% of participants lost ≥15%). Phase 3 is now enrolling for both obesity and liver disease:
- ▸ SYNCHRONIZE-1: 726 participants enrolled. Primary obesity efficacy trial. Results expected 2026.
- ▸ SYNCHRONIZE-2: 755 participants. T2D and weight management co-primary endpoints. Results expected 2026.
- ▸ LIVERAGE: MASH (fatty liver) Phase 3 trial. Building on Phase 2's 62% MASH improvement — the best MASH data of any drug class.
- ▸ LIVERAGE-Cirrhosis: Extends LIVERAGE to the more advanced liver disease population.
The IMPACT Phase 2b trial published in The Lancet (2025) produced striking liver data — and an unexpected second indication emerged:
- ▸ IMPACT (Lancet 2025): 48-week results. Liver fat reduced 54.7% with 1.8mg vs −8.2% placebo. ELF score (liver fibrosis marker) improved −0.58 vs +0.16 placebo. Liver stiffness −3.97 kPa vs −0.03 kPa placebo. Body weight −7.5% vs −0.2% placebo.
- ▸ RECLAIM trial: Pemvidutide is being evaluated for alcohol use disorder (AUD). GLP-1 receptor activation appears to dampen reward pathway responses to alcohol — potentially extending this drug class into addiction medicine.
- ▸ GLORY-2 (2025): 20.1% body weight loss at 60 weeks. 48.7% of participants achieved ≥20% weight loss — a bariatric-surgery-level threshold.
- ▸ DREAMS-3 (2025): Head-to-head vs semaglutide in T2D. Mazdutide won: 48% of participants achieved both A1C <7% and ≥10% weight loss vs 21% on semaglutide.
- ▸ Approved for obesity: China, June 2025 — first dual GLP-1/glucagon agonist approved anywhere in the world.
- ▸ Approved for T2D: China, September 2025. Real-world data is now accumulating from the Chinese market — the first such data for any dual agonist globally.
Complete Pipeline Comparison
All 5 pipeline drugs compared against current leaders (semaglutide, tirzepatide, retatrutide).
| Drug | Company | Mechanism | Route | Weight Loss | Timeline | Status |
|---|---|---|---|---|---|---|
| Orforglipron | Eli Lilly | GLP-1 | Oral | 12.4% (72w) | FDA 2026 | Phase 3 |
| Cagrisema | Novo Nordisk | GLP-1 + Amylin | Weekly Inj | 20.4% (68w) | Late 2026 | NDA Filed |
| Survodutide | Boehringer/Zealand | GLP-1 + GcG | Weekly Inj | 62% MASH | 2026-27 | Phase 3 |
| Pemvidutide | Altimmune | GLP-1 + GcG | Weekly Inj | 54.7% liver fat | 2026 | Phase 3 |
| Mazdutide | Innovent/Lilly | GLP-1 + GcG | Weekly Inj | 20.1% | Approved | China 2025 |
| Retatrutide | Eli Lilly | GLP-1 + GIP + GcG | Weekly Inj | 28% (48w) | 2026 | Phase 3 |
| Tirzepatide | Eli Lilly | GLP-1 + GIP | Weekly Inj | 22.5% (72w) | Approved | FDA Approved |
| Semaglutide | Novo Nordisk | GLP-1 | Weekly Inj | 15% (68w) | Approved | FDA Approved |
When Will They Be Available?
Expected approval timeline for the top 5 GLP-1 pipeline drugs.
Mechanism & Target Population
How each pipeline drug targets different pathways and patient populations.
Which Drug Is Right For You?
Target populations for each pipeline drug based on mechanism and trial data.
- needle-averse patients who want GLP-1 benefits
- Those who can't tolerate injections weekly
- Patients wanting convenience (no food timing)
- Those preferring oral medication options
- Anyone with good adherence to daily pills
- Maximum weight loss with established semaglutide backbone
- Those who've responded well to semaglutide
- Patients wanting proven dual mechanism
- Novo Nordisk brand loyalists
- Those with type 2 diabetes (improved HbA1c)
- Patients with MASH/NAFLD (fatty liver disease)
- Those needing direct liver fat clearance
- Breakthrough Therapy — priority review likely
- Patients who need both weight loss + liver health
- Those who've plateaued on current GLP-1s
- Liver-focused weight loss (54.7% liver fat reduction)
- Patients interested in addiction research (AUD)
- Balanced GLP-1/glucagon ratio preference
- Those in clinical trials (Phase 3 starting 2026)
- Combination of obesity + fatty liver
- Access to first approved dual agonist (China)
- Head-to-head semaglutide beater (DREAMS-3)
- T2D patients (beat semaglutide on HbA1c)
- Those wanting proven efficacy data
- Access to global markets (eventual US/EU)
- Triple agonist showing 28% weight loss
- Highest efficacy of any GLP-1 to date
- FDA decision expected 2026
- GLP-1 + GIP + glucagon all in one
- May become new gold standard
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Key Takeaways
- 5 advanced GLP-1 pipeline drugs with Phase 2+ data
- Orforglipron: first true oral small-molecule GLP-1 (FDA 2026)
- Cagrisema: NDA submitted December 2025, potential late 2026 approval
- Mazdutide: approved in China (2025), first dual agonist anywhere
- Survodutide: 62% MASH improvement (best ever), Breakthrough designation
- Pemvidutide: 54.7% liver fat reduction, also being studied for AUD
- Retatrutide (triple agonist) leads with 28% weight loss
- Dual/triple agonists appear more effective than GLP-1 alone
- Final FDA approval timelines (subject to change)
- Pricing and insurance coverage for new drugs
- Long-term safety data (most trials ongoing)
- Comparative head-to-head trials between pipeline drugs
- Real-world efficacy vs clinical trial conditions
- Optimal sequencing between different mechanisms
- Combination effects with other medications
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This page is for educational and informational purposes only. The drugs discussed are research compounds and pipeline drugs not yet approved by the FDA (except mazdutide in China). All data cited comes from clinical trials and published research. Dosages, timelines, and approval statuses are subject to change. Always consult a qualified, licensed healthcare provider before starting any new medication. Nothing on this page constitutes medical advice. Clinical trial data shown from different studies — direct comparisons should be made with caution.