Next-Generation Incretins: Retatrutide, Mazdutide, Survodutide
The next wave of incretin peptides adds glucagon receptor agonism to GLP-1, and in the case of retatrutide also GIP. Mazdutide is approved in China; retatrutide and survodutide are investigational drugs in phase 3. None has an approved use in the US or EU, and all are injectable.
Why add glucagon
Glucagon receptor activation raises energy expenditure and promotes hepatic fat oxidation, while GLP-1 agonism offsets glucagon's tendency to raise glucose. The combination targets greater weight loss and liver fat reduction than GLP-1 alone. Balancing receptor potencies is the design challenge, since too much glucagon activity raises heart rate and glucose. Retatrutide adds GIP agonism to that pairing. Clinical data so far show large weight reductions, with heart rate increases and gastrointestinal effects as the main tolerability questions under study.
The three molecules and their status
Retatrutide (LY3437943, Eli Lilly) is a GIP, GLP-1 and glucagon receptor triple agonist; its phase 2 trial reported mean weight reduction of 24.2% at 48 weeks at the top dose, and the phase 3 TRIUMPH program has reported positive topline results. Mazdutide (IBI362/LY3305677, Innovent) is a GLP-1 and glucagon dual agonist approved by China's NMPA in 2025 for chronic weight management and later for type 2 diabetes. Survodutide (BI 456906, Boehringer Ingelheim) is a GLP-1 and glucagon dual agonist in phase 3 for obesity and for MASH. Unapproved peptides are covered by WADA's S0 category.
Delivery profile
All three are acylated peptides of roughly 4 to 5 kDa designed for once-weekly subcutaneous injection, with albumin binding for extended half-life. They share the oral barriers of semaglutide and tirzepatide. Gastrointestinal adverse events during dose escalation are a class issue, and slower absorption profiles are one lever developers use to manage them. Their long half-lives already solve dosing frequency, so any delivery work must add a different benefit, such as smoother exposure or a non-injected route.
What this means for delivery research
Each new multi-agonist increases the value of an alternative to weekly injection, but also raises the bar: a delivery system must preserve the balanced receptor activity of a large, engineered peptide. In practice this means release profile, peptide integrity and receptor-level activity all need to be measured together. For companies licensing these molecules in new regions, formulation work may also be part of registering local presentations. Vegalab works only with holders of legitimate rights to such molecules.
Key facts
- Retatrutide produced mean weight reduction of 24.2% at 48 weeks at the 12 mg dose in a phase 2 trial (Jastreboff et al. 2023, N Engl J Med 389:514)
- Mazdutide received NMPA approval in China for chronic weight management in 2025 as the first GLP-1 and glucagon dual agonist approved (Innovent Biologics press release, June 2025)
- Survodutide reduced body weight by up to 14.9% at 46 weeks in a phase 2 obesity trial (le Roux et al. 2024, Lancet Diabetes Endocrinol 12:162)
- Non-approved substances with no current approval for human therapeutic use are prohibited at all times under S0 (WADA Prohibited List 2026)
How our delivery technology applies
These peptides are research reference compounds for our delivery work, not products. The glucagon component makes pharmacokinetic smoothing relevant: a depot or controlled-release layer that lowers peak concentration could matter for tolerability. Multi-layer particles allow release rate to be tuned separately from protease protection, which is how we would approach feasibility for a partner who owns such a molecule.
Own a multi-agonist peptide? Scope a controlled-release feasibility study with us.
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