Retatrutide

Grade B: Human evidence, not approved for this use

TL;DR: 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 includes multiple pivotal trials across obesity, type 2 diabetes, and cardiovascular outcomes populations, with TRIUMPH-1 (obesity without T2D, n=2,339) reporting 28.3% mean weight loss at 12 mg at 80 weeks and TRIUMPH-4 (obesity with knee osteoarthritis) reporting 28.7% mean weight loss at 12 mg, as of early 2026. TRIUMPH data have not yet supported regulatory submission as of June 2026; the compound remains not approved by FDA. Evidence strength is Grade B due to ongoing Phase 3 status without regulatory approval.

Key Takeaways

Grade B: Human evidence, not approved for this use
Not FDA approved: Investigational; Phase 3 TRIUMPH trials ongoing as of June 2026, no NDA submitted.
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 permissible under current FDA policy.

Mechanism

Simultaneously activates GLP-1, GIP, and glucagon receptors to suppress appetite, enhance insulin secretion in a glucose-dependent manner, and increase energy expenditure.

Evidence

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 includes multiple pivotal trials across obesity, type 2 diabetes, and cardiovascular outcomes populations, with TRIUMPH-1 (obesity without T2D, n=2,339) reporting 28.3% mean weight loss at 12 mg at 80 weeks and TRIUMPH-4 (obesity with knee osteoarthritis) reporting 28.7% mean weight loss at 12 mg, as of early 2026. TRIUMPH data have not yet supported regulatory submission as of June 2026; the compound remains not approved by FDA. Evidence strength is Grade B due to ongoing Phase 3 status without regulatory approval.

Safety and risks

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 of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2) were excluded from TRIUMPH trials and should not use GLP-1 receptor agonists. Gastrointestinal adverse events are the dominant safety signal and were more frequent than those seen with GLP-1 mono-agonists: nausea, vomiting, and diarrhea were common across dose groups in both Phase 2 and Phase 3 data. A newly identified safety signal is dysesthesia (abnormal skin sensations including tingling, numbness, and burning), affecting approximately 12.5% of participants in TRIUMPH-1 and 20.9% in TRIUMPH-4 at the 12 mg dose versus under 1% on placebo; the mechanism and long-term significance remain under investigation. Standard GLP-1 class precautions apply: risk of acute pancreatitis, acute gallbladder disease, acute kidney injury from volume depletion, and pulmonary aspiration risk during anesthesia due to delayed gastric emptying. The full risk profile is not established; safety data reflect clinical trial populations and may not capture rare or long-term harms.

Interactions

No approved label exists; class-level interactions anticipated (insulin secretagogues increase hypoglycemia risk; delayed gastric emptying may alter absorption of oral medications). Confirm at prescribing.

Compounding legality

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 permissible under current FDA policy.

Sources

Retatrutide is Not FDA approved. PeptideGrids presents evidence and regulatory status for informational purposes only. We do not sell, supply, source, or help anyone obtain this compound, and we provide no dosing or administration guidance. This is not medical advice; consult a licensed clinician. Full disclaimer.

Last reviewed June 1, 2026 by PeptideGrids editorial team (independently audited).