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Beyond GLP-1: The Next Obesity Research Wave
Short answer: semaglutide and tirzepatide opened the incretin era; the next research wave moves past pure GLP-1 . Six compounds define it: MariTide (GLP-1 agonist + GIP antagonist , monthly), CagriSema (amylin + GLP-1), amycretin (one molecule, amylin + GLP-1, oral and injectable), survodutide (GLP-1 + glucagon), petrelintide (a clean amylin analogue), and orforglipron (the first oral non-peptide GLP-1 pill). None has marketing authorisation anywhere in the world as of mid-2026. This page maps each mechanism and the latest trial data, and links to a deep research guide on every one.
For three years the obesity conversation has been a two-horse race: semaglutide (Wegovy / Ozempic) and tirzepatide (Mounjaro / Zepbound). That race is over. The frontier has moved to new receptor combinations, new dosing cadences, and the first oral pill — and search demand is racing ahead of approval, exactly as it did with retatrutide. This is the pillar overview of that pipeline. Each compound below has its own full research guide; this page is the map.
Plain-English summary. Every compound on this page is investigational . As of mid-2026 none is an approved medicine — two (CagriSema, orforglipron) have regulatory filings in progress, the rest are mid-trial. Research-grade reference peptides are a separate, lawful category: lyophilised reagents labelled research use only, not for human consumption . New-U sells only research reagents, and only for the established compounds in the class. This page is general information, not legal or medical advice; do not use unapproved compounds on people.
The four frontiers beyond GLP-1
The whole pipeline can be understood as four moves away from a plain GLP-1 agonist:
The next wave at a glance
Figures are headline means from the trials cited in each linked guide; populations, durations and analysis methods differ, so the column is not a like-for-like ranking. None of these compounds is approved as a medicine anywhere in the world as of mid-2026.
MariTide — the monthly injection
Amgen’s maridebart cafraglutide (formerly AMG 133) is the structural outlier: a peptide–antibody conjugate with a ~21-day half-life, three times semaglutide’s, enabling once-monthly dosing. Mechanistically it is also contrarian — it agonises GLP-1 but antagonises GIP, the receptor tirzepatide activates. The Phase 2 trial (NEJM, 2025) reported up to ~20% mean weight loss at 52 weeks without a plateau. Full profile: MariTide research guide.
CagriSema — amylin meets GLP-1
Novo Nordisk’s CagriSema is a fixed-dose combination of cagrilintide (a long-acting amylin analogue) and semaglutide. The Phase 3 REDEFINE 1 trial reported ~22.7% mean weight loss at 68 weeks, with 40% of participants losing ≥25% of body weight — though it landed below Novo’s own ~25% target. Both components are catalogued by New-U as research references. Full profile: CagriSema research guide.
Amycretin — two hormones, one molecule, a pill option
Amycretin folds amylin and GLP-1 agonism into a single molecule that Novo is developing in both a once-daily oral and a once-weekly subcutaneous form. The Phase 2 diabetes readout reported up to ~14.5% weight loss (subcutaneous) and ~10.1% (oral). Full profile: amycretin research guide.
Survodutide — the liver play
Boehringer Ingelheim and Zealand’s survodutide is a GLP-1 + glucagon dual agonist whose glucagon arm makes it as much a liver drug as a weight drug: it holds FDA Breakthrough Therapy status for MASH, and the Phase 3 SYNCHRONIZE-1 obesity trial met both primary endpoints. Full profile: survodutide research guide.
Petrelintide — the clean amylin
Zealand’s petrelintide (Roche-partnered) is a long-acting amylin analogue positioned as a foundational therapy — the Phase 2 headline (~10.7% at 42 weeks) was more modest than the incretins, but the story was tolerability: at the top dose, no vomiting and no GI-driven discontinuations. Full profile: petrelintide research guide.
Orforglipron — the first real pill
Eli Lilly’s orforglipron is the one that could change distribution economics: a small-molecule, non-peptide GLP-1 agonist that works as a once-daily tablet with no food or water restriction. The Phase 3 ATTAIN-1 trial reported ~12.4% at 72 weeks, and Lilly has triggered global regulatory submissions. Full profile: orforglipron research guide.
What to watch in 2026–2027
Where research compounds fit
These six molecules are mostly proprietary investigational compounds; no legitimate research supplier catalogues MariTide or survodutide. What is available, lawfully, is the established research-reference set in the same pharmacological class — the molecules the literature has characterised and that suppliers can verify to >99% HPLC purity:
Each is sold as a sealed, lyophilised reference peptide with a per-batch Certificate of Analysis, research use only, not for human consumption . The newer pipeline compounds are covered here as research literature , not as products.
Frequently Asked Questions
What comes after semaglutide and tirzepatide? Amylin analogues, amylin+GLP-1 unimolecular agonists, GLP-1/glucagon dual agonists, GLP-1 agonist + GIP antagonist conjugates, and oral non-peptide GLP-1 small molecules. The six leading examples are mapped above.
Which has shown the most weight loss? Of the compounds linked here, injectable retatrutide reported the largest single mean (~24% / 48 wks, Phase 2); among the newer pipeline, CagriSema (~22.7% / 68 wks) and MariTide (~20% / 52 wks) lead. Trial designs differ, so these are not strictly comparable.
Are any approved? No. As of mid-2026 none has marketing authorisation. CagriSema and orforglipron have regulatory filings in progress; the rest are in Phase 2 or 3.
Is orforglipron a peptide? No — it is an oral small molecule, which is why it can be a daily tablet rather than an injection.
Does New-U sell these? The pipeline molecules are proprietary and not catalogued. New-U does carry the class’s research references — cagrilintide, semaglutide, tirzepatide, retatrutide — research use only.
Related Reading
Primary sources & further reading
External links are provided for research reference only; New-U is not affiliated with the cited organisations and links carry no endorsement either way.
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