Semaglutide vs Retatrutide
How Semaglutide and Retatrutide differ on mechanism, dosing, and the strength of the evidence behind each.
How this is graded
Every compound below carries a REGEN research grade, from S (regulatory approval behind the use it is bought for) down to F (no clinical evidence). Ordering follows that grade rather than search volume, so the compound at the top is the one with the most evidence, not the one most often sold. Doses are those reported in published protocols and are not recommendations.
Semaglutide
Semaglutide is a long-acting GLP-1 (glucagon-like peptide-1) receptor agonist that slows gastric emptying, increases satiety, and improves insulin sensitivity and glucose control. Originally developed for type 2 diabetes, it has become a leading weight-loss therapy. Dosing is titrated up slowly over weeks to minimize gastrointestinal side effects like nausea. It directly affects metabolic markers — expect improvements in HbA1c, fasting glucose, and body composition. Not typically stacked with growth or healing peptides; used as a standalone metabolic tool.
Retatrutide
Retatrutide (LY3437943) is an investigational triple receptor agonist that activates the GIP, GLP-1, and glucagon receptors — informally a ‘GLP-3’ for adding glucagon agonism on top of the dual mechanism of tirzepatide. The added glucagon activity raises energy expenditure alongside the appetite suppression and improved glucose control of the incretin pathways, and phase 2 trials reported some of the largest average weight reductions seen for any single agent to date. It is dosed once weekly subcutaneously and titrated slowly to manage gastrointestinal side effects. As an investigational compound it is not FDA-approved; monitor metabolic markers and titrate per protocol.
Evidence compared
| Semaglutide | Retatrutide | |
|---|---|---|
| Research grade | Sgrade | Agrade |
| Reported dose | 0.25–2.4 mg | 1–12 mg |
| Frequency | 1x weekly (titrated) | 1x weekly (titrated) |
| Half-life | ~7 days | ~6 days |
| Routes | subcutaneous, oral | subcutaneous |
| Tracked outcomes | Weight Loss, Immune Function, Body Composition, Muscle Growth, Cognitive Function | Weight Loss, Immune Function, Body Composition, Muscle Growth |
| Contraindications | personal/family history of medullary thyroid carcinoma, MEN 2, pancreatitis, pregnancy | personal/family history of medullary thyroid carcinoma, MEN 2, pancreatitis, pregnancy |
Which has more behind it
Semaglutide carries the stronger evidence grade (S) against Retatrutide at A, which means more of what is claimed for Semaglutide has been tested in humans. Both entries link through to the full reference, where the trial list and citations for each claim are set out in full.
Full Semaglutide reference · Full Retatrutide reference
At a glance
| Compound | Grade | Reported dose | Half-life |
|---|---|---|---|
| Semaglutide | Sgrade | 0.25–2.4 mg · 1x weekly (titrated) | ~7 days |
| Retatrutide | Agrade | 1–12 mg · 1x weekly (titrated) | ~6 days |
Frequently asked questions
Semaglutide or Retatrutide, which has better evidence?
Semaglutide carries the stronger evidence grade (S) against Retatrutide at A, which means more of what is claimed for Semaglutide has been tested in humans.
Can Semaglutide and Retatrutide be used together?
The catalog does not list Semaglutide and Retatrutide as a common pairing. Combining compounds does not combine their evidence.
What doses are reported for Semaglutide?
Published protocols report 0.25–2.4 mg, 1x weekly (titrated). This is what the literature describes, not a recommendation.
References
- Once-Weekly Semaglutide in Adults with Overweight or Obesity · Wilding JPH, et al. · 2021
- FDA Approval Announcement for Wegovy (2021). · 2021
- Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. · Lincoff AM, Brown-Frandsen K, Colhoun HM et al. · 2023
- Semaglutide, a glucagon like peptide-1 receptor agonist with ... - NIH · Mahapatra MK, Karuppasamy M, Sahoo BM · 2022
- Semaglutide Mechanism of Action Review. PMC. · Ghusn W, De la Rosa A, Sacoto D, Cifuentes L, Campos A, Feris F, Hurtado MD, Acosta A · 2022
- Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes. · McGuire DK, Marx N, Mulvagh SL et al. · 2025
- Semaglutide | C187H291N45O59 | CID 56843331 - PubChem - NIH
- Central Nervous System Effects of GLP-1 Agonists. Nature Medicine.
- Effects of oral semaglutide on cardiovascular outcomes in individuals with type 2 diabetes and established atherosclerotic cardiovascular disease and/or chronic kidney disease: Design and baseline characteristics of SOUL, a randomized trial. · McGuire DK, Busui RP, Deanfield J et al. · 2023
- Semaglutide - StatPearls - NCBI Bookshelf
- Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). NEJM. 2021. · Wilding JP, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MT, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF · 2021
- Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. · Perkovic V, Tuttle KR, Rossing P et al. · 2024
- Molecular mechanisms of semaglutide and liraglutide as a ... · Tamayo-Trujillo R, Ruiz-Pozo VA, Cadena-Ullauri S, Guevara-Ramírez P, Paz-Cruz E, Zambrano-Villacres R, Simancas-Racines D, Zambrano AK · 2024
- Triple–Hormone–Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial · Jastreboff AM, et al. · 2023
- Jastreboff AM, et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity, A Phase 2 Trial. N Engl J Med. 2023;389:514-526. · Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML · 2023
- Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials. · Giblin K, Kaplan LM, Somers VK et al. · 2026
- Appetite, eating attitudes, and eating behaviours during treatment with retatrutide in adults with type 2 diabetes: Results of a phase 2 study · Kanu C, Boye KS, Poon JL, Goetz I, Williamson S, Lou J, Hartman ML, Martin CK, Coskun T · 2025
- Rosenstock J, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial. Lancet. 2023;402(10401):529-544. · Rosenstock J, Frias J, Jastreboff AM, Du Y, Lou J, Gurbuz S, Thomas MK, Hartman ML, Haupt A, Milicevic Z, Coskun T · 2023
- Effects of retatrutide on body composition in people with type 2 diabetes. Lancet Diabetes Endocrinol. 2025. · 2025
- Tirzepatide Once Weekly for the Treatment of Obesity · Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A · 2022
- Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist. PMC. 2024. · Abdrabou Abouelmagd A, Abdelrehim AM, Bashir MN, Abdelsalam F, Marey A, Tanas Y, Abuklish DM, Belal MM · 2025
- Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial. · Coskun T, Wu Q, Schloot NC et al. · 2025
- Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatohepatitis. Nature Medicine. 2024. · 2024
- Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. · Sanyal AJ, Kaplan LM, Frias JP et al. · 2024