Retatrutide (LY3437943): NOT FDA Approved

What it is

• Retatrutide is an investigational, once-weekly injectable “triple agonist” targeting GLP-1 + GIP + glucagon receptors (“triple-G”). Mechanistically, this combines appetite suppression/satiety (GLP-1, GIP) with added energy-expenditure and metabolic effects attributed in part to glucagon-receptor activity.  
• Status (Jan 22, 2026): Not FDA-approved for weight loss or any indication.

Trial landscape (what we know so far)

Phase 2 (Obesity; 48 weeks)

• NEJM phase 2 obesity study showed large mean weight reductions at 48 weeks; Lilly reported up to ~24.2% mean weight loss in a secondary endpoint at the higher doses.  

Phase 3 (TRIUMPH program; multiple indications)

• TRIUMPH-4 (obesity/overweight + knee OA; 68 weeks): Lilly’s topline results report up to 28.7% mean weight loss at 68 weeks (12 mg arm) with meaningful OA pain/function improvements.  
• Safety signal to watch: reporting around TRIUMPH-4 has flagged dysesthesia (abnormal sensation) as a potentially emerging signal (details will depend on full peer-reviewed data).  
• Ongoing/registered trials span obesity, T2D/obesity phenotypes, CV outcomes and other comorbidity studies on ClinicalTrials.gov.  

Side effects  (based on class + trial experience)

Most common (class-typical)

• GI: nausea, vomiting, diarrhea, constipation, abdominal discomfort, reflux-like symptoms; typically dose-dependent and most prominent during titration.

Potentially serious (rare but important)

• Pancreatitis, gallbladder disease, dehydration/AKI (often in the context of GI losses), severe GI intolerance. (Counsel similarly to GLP-1 class until retatrutide label data exist.)

Clinical pearl for high-touch practices

• Many “bad experiences” are titration/education failures: unclear units, rapid escalation, inadequate constipation prevention, low protein intake → fatigue + lean mass loss.

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Grey-market cautions (strongly recommend saying this out loud)

1) “Research peptide” retatrutide is a red flag

• FDA has sent warning letters to online sellers marketing unapproved GLP-1 ingredients (including sites that also offered retatrutide) under “research use only” messaging.  

2) Compounded retatrutide: major regulatory risk

• Retatrutide does not appear on the 503B Bulks List and is not on the FDA drug shortage list, so (per the Ohio Board of Pharmacy-posted FDA letter) it would not qualify for outsourcing-facility compounding under those conditions.  
• FDA has also issued warning-letter content indicating certain “compounded retatrutide” products are unapproved/misbranded.  

3) Counterfeit and fraudulent GLP-1 supply is real

• FDA has warned about fraudulent compounded semaglutide/tirzepatide with false labels (including pharmacies that do not exist or did not compound the product).  
• FDA also warned about counterfeit Ozempic in the U.S. supply chain (lot PAR0362 + serial starting 51746517).  

4) Even “compounded semaglutide” has pitfalls

• FDA notes some compounded products use semaglutide salt forms (e.g., semaglutide sodium/acetate), which are different active ingredients than in approved products and FDA states it is not aware of a lawful basis for their use in compounding.  

Bottom line for patients:

“If it’s not dispensed through a legitimate, licensed pharmacy supply chain under a valid prescription—and especially if it’s sold as a peptide—assume you’re taking a purity/sterility/dose-accuracy gamble.”

Our concierge workflow

• We offer FDA-approved: Wegovy/Zepbound (or diabetes-indicated products when appropriate), with slow titration + side-effect protocol.
• If retatrutide interest persists: we provide trial pathway options (ClinicalTrials.gov search + referral).
• If still requested, we will document: patient requested investigational drug; we counseled not approved, trial-only, and reviewed grey-market risks.

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