Semaglutide vs Tirzepatide vs Retatrutide
A side-by-side comparison of Semaglutide, Tirzepatide, Retatrutide by independent evidence grade, FDA status, mechanism of action, key safety considerations, and which FDA 503B outsourcing facilities report compounding each.
| Semaglutide | Tirzepatide | Retatrutide | |
|---|---|---|---|
| Evidence grade | Grade A: Approved and proven | Grade A: Approved and proven | Grade B: Human evidence, not approved for this use |
| FDA status | FDA approved Approved as Ozempic (subcutaneous injection, type 2 diabetes), Wegovy (subcutaneous injection 2.4 mg and oral 25 mg tablet, chronic weight management and cardiovascular risk reduction in obesity), and Rybelsus (oral tablet, type 2 diabetes). | FDA approved Approved as Mounjaro (subcutaneous injection, type 2 diabetes) and Zepbound (subcutaneous injection, chronic weight management and, additionally, obstructive sleep apnea in adults with obesity). | Not FDA approved Investigational; Phase 3 TRIUMPH trials ongoing as of June 2026, no NDA submitted. |
| Mechanism | Semaglutide is a GLP-1 receptor agonist that stimulates glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and reduces appetite via central and peripheral GLP-1 receptor activation. | Tirzepatide is a dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 receptor agonist, which stimulates insulin secretion, suppresses glucagon, reduces appetite, and slows gastric emptying through activation of both receptor pathways. | Simultaneously activates GLP-1, GIP, and glucagon receptors to suppress appetite, enhance insulin secretion in a glucose-dependent manner, and increase energy expenditure. |
| Key safety | Boxed warning: semaglutide causes thyroid C-cell tumors in rodents at clinically relevant exposures; human relevance is unknown but it is contraindicated in... | Boxed warning: tirzepatide causes thyroid C-cell tumors in rats at clinically relevant exposures; human relevance is unknown and the drug is contraindicated in... | As a GLP-1 receptor agonist, retatrutide carries the class risk of thyroid C-cell tumors observed in rodent studies; patients with personal or family history... |
What the evidence shows
Semaglutide A
Semaglutide has the broadest and strongest human evidence base among GLP-1 receptor agonists currently approved for weight management and type 2 diabetes. The STEP clinical trial program, comprising multiple large phase 3 randomized controlled trials, demonstrated clinically meaningful weight loss in adults with...
Compounding: FDA-approved; brand and generic forms available. Mass compounding from bulk API by 503A and 503B facilities was permitted during a declared shortage; the semaglutide shortage was resolved by FDA in...
Tirzepatide A
Tirzepatide is approved by the FDA for type 2 diabetes (Mounjaro) and chronic weight management (Zepbound), supported by an extensive phase 3 trial program. The SURPASS series of trials in type 2 diabetes demonstrated substantial reductions in HbA1c and body weight, with tirzepatide outperforming comparator GLP-1...
Compounding: FDA-approved; brand name only (no generic as of mid-2026). Mass compounding from bulk API was permitted during a declared shortage that FDA resolved in December 2024; enforcement grace periods for...
Retatrutide B
Retatrutide is an investigational once-weekly injectable triple agonist targeting GLP-1, GIP, and glucagon receptors, developed by Eli Lilly for obesity and type 2 diabetes. Phase 2 RCT data (published in NEJM) demonstrated up to approximately 24% mean body weight loss over 48 weeks. The Phase 3 TRIUMPH program...
Compounding: Not approved by FDA as of June 2026. Retatrutide is not on any FDA 503A or 503B compounding candidate list; compounding of unapproved investigational agents for non-trial use is not legally...
Where these are compounded
Semaglutide: reported compounded by Annovex Pharma, Inc., Apollo Care, BPI Labs LLC, Delta Pharma, Inc., Eagle Pharma, Empower Clinic Services New Jersey, Empower Pharma, Fagron Compounding Services dba Fagron Sterile Services, and 9 more.
Tirzepatide: reported compounded by AnazaoHealth Corporation, Annovex Pharma, Inc., Apollo Care, BPI Labs LLC, Empower Pharma, Hybrid Pharma, LLC, Olympia Pharmaceuticals, PQ Pharmacy LLC, and 2 more.
Retatrutide: no FDA 503B facility in our directory currently reports compounding it.
From the FDA Outsourcing Facility Product Report. PeptideGrids does not sell or source any compound.
Full profiles: Semaglutide, Tirzepatide, Retatrutide. Browse all GLP-1s and therapeutic peptides.