The GLP-1 market is evolving rapidly. Today's options—Wegovy and Zepbound—will soon be joined by next-generation medications promising better efficacy, improved convenience, or both. This guide covers every major candidate in development.
Pipeline Overview: What's Coming When
| Drug | Manufacturer | Type | Est. Approval | Weight Loss |
|---|---|---|---|---|
| Orforglipron | Eli Lilly | Oral GLP-1 | Q1 2026 | ~12-15% |
| CagriSema | Novo Nordisk | GLP-1 + Amylin | Late 2026 | ~22.7% |
| Retatrutide | Eli Lilly | Triple Agonist | 2027 | ~28.7% |
| Survodutide | Boehringer/Zealand | GLP-1 + Glucagon | 2027 | ~18.7% |
| Amycretin | Novo Nordisk | Oral GLP-1/Amylin | 2028-2029 | ~15%+ |
| VK2735 | Viking | GLP-1 + GIP | 2027 | ~14.7% |
Orforglipron (Eli Lilly) — Coming Q1 2026
The headline: An oral GLP-1 you can take with food and water.
Mechanism: Small molecule GLP-1 agonist (not a peptide). Because it's not a peptide, it doesn't require the SNAC permeation enhancer that oral Wegovy needs.
Key advantage: No food or water restrictions. Take it whenever, with whatever. This is the main differentiator from oral semaglutide.
Efficacy data:
- ATTAIN-MAINTAIN trial: Patients switching from injectable Wegovy or Zepbound maintained 99% of weight loss over 52 weeks
- ACHIEVE-3 (vs. Rybelsus): Superior A1c reduction (-1.9% vs -1.1%) and weight loss (-14.6 lbs vs -7.9 lbs)
- Standalone weight loss: ~12-15%
Strategic positioning: Orforglipron is positioned as a maintenance medication. Start with injectable Zepbound for maximum initial weight loss, then transition to oral orforglipron for long-term maintenance. This "induction → maintenance" model could become standard.
Timeline: NDA submitted late 2025, Priority Voucher applied. Approval expected Q1 2026—potentially imminent.
CagriSema (Novo Nordisk) — Late 2026
The headline: Novo's answer to tirzepatide—combining semaglutide with a different partner hormone.
Mechanism: Fixed-dose combination of semaglutide + cagrilintide (amylin analog). Unlike tirzepatide (GLP-1 + GIP), CagriSema pairs GLP-1 with amylin—a hormone that promotes satiety through a distinct pathway.
Efficacy data:
- REDEFINE 1 (obesity): 22.7% weight loss at 68 weeks
- 41% of participants achieved ≥25% weight loss
- REDEFINE 2 (T2D + obesity): 15.7% weight loss with robust A1c control
The disappointment: Investors expected ≥25% average weight loss to clearly beat tirzepatide. At 22.7%, CagriSema is better than semaglutide alone but doesn't decisively surpass tirzepatide.
Strategic positioning: CagriSema provides an alternative mechanism for patients who don't respond well to GIP-based therapy. It's Novo's competitive response to Lilly's dual agonist success.
Retatrutide (Eli Lilly) — 2027
The headline: 28.7% weight loss approaches bariatric surgery.
Mechanism: Triple agonist (GLP-1 + GIP + Glucagon). The glucagon component drives additional fat burning and energy expenditure.
Efficacy data:
- TRIUMPH-4: 28.7% weight loss at 12mg dose over 68 weeks
- Average absolute loss: 71.2 lbs (32.3 kg)
- Approaches bariatric surgery efficacy (~30-35%)
Safety signal: Dysesthesia (unusual skin sensations) in 20.9% at high dose. Discontinuation rate of 18.2%—higher than current GLP-1s.
Strategic positioning: The "nuclear option" for severe obesity. Maximum efficacy for patients who need aggressive intervention. Not for everyone due to side effect burden.
Survodutide (Boehringer/Zealand) — 2027
The headline: Best-in-class for MASH (liver disease).
Mechanism: Dual agonist (GLP-1 + Glucagon). Different receptor balance than retatrutide.
Efficacy data:
- Weight loss: ~18.7% in Phase 2
- MASH: 83% resolution in Phase 2 trials
- FDA Breakthrough Therapy designation for MASH
Strategic positioning: May become the leading MASH treatment rather than competing primarily on weight loss. For patients with fatty liver disease, survodutide could be the preferred choice.
Amycretin (Novo Nordisk) — 2028-2029
The headline: The "holy grail"—high efficacy in an oral pill.
Mechanism: Unimolecular GLP-1/Amylin co-agonist. Essentially CagriSema's mechanism in a single molecule, available in both oral and injectable forms.
Early data:
- Phase 2: 13.1% weight loss at just 12 weeks (oral formulation)
- Significantly faster weight loss trajectory than oral Wegovy
- Phase 2 in T2D: 14.5% weight loss over 36 weeks
Strategic significance: If oral amycretin can match injectable efficacy (~15%+ weight loss) without food restrictions, it could eventually cannibalize the entire injectable market. This is Novo's long-term oral strategy.
VK2735 (Viking Therapeutics) — 2027
The headline: A potential acquisition target validating the dual agonist mechanism.
Mechanism: GLP-1/GIP dual agonist (similar to tirzepatide).
Efficacy data:
- VENTURE Phase 2: 14.7% weight loss at 13 weeks
- Oral Phase 1: 5.3% weight loss in just 28 days
Strategic note: Viking is a small biotech company. If VK2735 continues showing strong results, acquisition by a larger pharma company is likely. This drug validates that tirzepatide's mechanism works outside of Lilly's specific molecule.
Pemvidutide (Altimmune) — 2028
The headline: "Quality" weight loss with best-in-class muscle preservation.
Mechanism: GLP-1/Glucagon dual agonist (1:1 balanced ratio).
Key differentiator: IMPACT 48-week results showed only 21.9% of weight lost was lean mass—versus ~40% for typical GLP-1s. This is the best muscle preservation data in the class.
Trade-off: Lower overall weight loss (~7.5%) compared to competitors. Pemvidutide positions for patients where body composition matters more than absolute weight—potentially bodybuilders, athletes, or older patients concerned about sarcopenia.
The Emerging Treatment Paradigm
As these drugs launch, expect treatment algorithms to evolve:
Induction phase (maximum weight loss):
- High-efficacy injectables: Zepbound → CagriSema → Retatrutide
- 6-18 months of aggressive therapy
Maintenance phase (weight stability):
- Transition to oral maintenance: Orforglipron or oral Wegovy
- Lower cost, greater convenience
- Indefinite duration
Special populations:
- MASH: Survodutide as first-line
- Muscle-conscious: Pemvidutide or pemvidutide + bimagrumab
- Severe obesity: Retatrutide
What This Means for Men
More options coming: If current medications don't work for you—due to efficacy, side effects, or cost—alternatives are 6-24 months away.
Oral convenience: Orforglipron (no food restrictions) arrives soon. If needles are your barrier, the wait is almost over.
Maximum efficacy available: Retatrutide's 28.7% weight loss will be available by 2027 for men needing aggressive intervention.
Testosterone implications: More effective weight loss should mean greater testosterone normalization. The ENDO 2025 tirzepatide data (77% normalization) may be exceeded by more potent medications.
Competition drives access: As more drugs launch, pricing competition should improve. Manufacturer direct programs, insurance negotiations, and generic timelines all favor patients long-term.
The next three years will bring more options, better efficacy, and improved convenience. If current treatments aren't working, the future is genuinely promising.