Retatrutide
Investigational triple agonist. Phase 2 reported the largest mean weight reduction yet published for a pharmacologic agent at 48 weeks. Phase 3 ongoing.
Metabolic & Weight
Survodutide
A weekly dual agonist in phase 3 for obesity, with phase 2 results in MASH showing high rates of histological improvement.
Overview
Survodutide activates two receptors at once. The GLP-1 arm reduces appetite and slows the stomach, which is the familiar mechanism. The glucagon arm does something different: it increases the rate at which the body burns energy and the liver oxidises fat. Glucagon alone would raise blood sugar, but the GLP-1 activity offsets that. The liver effect is why the most interesting results so far are in fatty liver disease rather than weight alone.
An acylated peptide dual agonist at the glucagon receptor and GLP-1 receptor with balanced potency, engineered with a C18 fatty-acid side chain for albumin binding and weekly dosing. GCGR agonism increases hepatic fatty acid oxidation and resting energy expenditure; GLP-1R agonism suppresses appetite and counters glucagon-driven hyperglycaemia. Phase 2 in biopsy-confirmed MASH reported MASH improvement without worsening fibrosis in a majority of treated participants at 48 weeks; phase 2 in obesity reported mean weight reduction approaching 19% at 46 weeks.
Research areas
ObesityMASHHepatic fat metabolism
Dosing reported in the literature
Every protocol below is reproduced from a published study or approved labelling, with its source named. These are records of what was studied — not recommendations, and not a suggestion that any of them is appropriate for any person.
| Protocol as reported | Source |
|---|---|
| Weekly subcutaneous dosing titrated over 20 weeks to 2.4, 3.6 or 4.8 mg, continued to week 46 | Le Roux et al., The Lancet Diabetes & Endocrinology 2024 |
| Weekly subcutaneous dosing to 2.4, 4.8 or 6.0 mg over 48 weeks in biopsy-confirmed MASH | Sanyal et al., New England Journal of Medicine 2024 |
Trial status
Phase 3 SYNCHRONIZE programme ongoing in obesity. Phase 2 completed in obesity and in MASH.
Reported safety signals
- Gastrointestinal adverse effects are frequent and drove most discontinuations in phase 2.
- Glucagon receptor agonism can raise heart rate and, in principle, blood glucose — both were monitored closely in trials.
- Long-term safety is unknown; the longest published exposure is under a year.
Common questions
Why add glucagon to a weight-loss drug?
Because glucagon increases energy expenditure and hepatic fat oxidation — it acts on the output side of the energy balance, where GLP-1 acts on intake. The pairing is deliberate: GLP-1 activity offsets glucagon's tendency to raise blood glucose.
Primary sources
Medical disclaimer
This page is for informational and research purposes only. Nothing here constitutes medical advice. The compounds discussed are research chemicals. Consult a qualified clinician before starting any protocol.
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