Retatrutide vs Tirzepatide: How the Two Research Compounds Differ

Short answer: tirzepatide acts on two hormone receptors (GIP and GLP-1) and is authorised as a medicine by the U.S. FDA. Retatrutide acts on three (GIP, GLP-1 and glucagon) and is still investigational: as of November 2026 it is not authorised as a medicine anywhere, and Eli Lilly plans to submit it to the FDA in the first quarter of 2027. Both come from Eli Lilly. The products in our store are for laboratory research use only.

How they work

Tirzepatide is a dual agonist of the GIP and GLP-1 receptors, two gut hormones involved in insulin release and appetite signalling. Retatrutide adds a third target, the glucagon receptor, which is involved in energy expenditure and liver fat metabolism. That third target is the main scientific difference between the two compounds.

Regulatory status

• Tirzepatide: authorised by the FDA in May 2022 for type 2 diabetes and, under a second brand name, in November 2023 for chronic weight management in adults with obesity, or overweight with a weight-related condition.
• Retatrutide: investigational. Lilly reported topline results of four Phase 3 TRIUMPH trials during 2026 and announced on 23 July 2026 that it plans to submit a Biologics License Application to the FDA in the first quarter of 2027. Until a regulator decides, the compound has no marketing authorisation.

What the trials reported

Trial	Compound	Participants	Length	Mean body-weight change (highest dose group)	Placebo
Phase 2 (NEJM 2023)	Retatrutide, 12 mg	Adults with obesity	48 weeks	−24.2%	−2.1%
SURMOUNT-1, Phase 3 (NEJM 2022)	Tirzepatide, 15 mg	Adults with obesity or overweight, without diabetes	72 weeks	−20.9%	−3.1%
TRIUMPH-1, Phase 3 (Lilly, 2026)	Retatrutide, 12 mg	2,339 adults with obesity or overweight, without diabetes	80 weeks	−28.3%	−2.2%
TRIUMPH-2, Phase 3 (Lilly, July 2026)	Retatrutide, 12 mg	1,152 adults with type 2 diabetes and obesity or overweight	80 weeks	−20.8%	−4.0%
TRIUMPH-3, Phase 3 (Lilly, July 2026)	Retatrutide, 12 mg	1,949 adults with BMI 35 or more and established cardiovascular disease	80 weeks	−22.6%	−3.2%
TRIUMPH-4, Phase 3 (Lilly, 2026)	Retatrutide	445 adults with obesity or overweight and knee osteoarthritis	68 weeks	up to −28.7%	not reported in the source

The TRIUMPH figures are topline results reported by Eli Lilly and are not yet peer-reviewed. These are separate trials with different participants, lengths and designs, so the numbers cannot be compared directly: no head-to-head trial of retatrutide against tirzepatide had been published when this page was written.

Safety findings reported in the trials

In the trials of both compounds, the most common adverse events were gastrointestinal (nausea, diarrhoea, vomiting and constipation), and they rose with the dose. In TRIUMPH-1, Lilly reported nausea in 42.4% of participants on 12 mg retatrutide against 14.8% on placebo, abnormal skin sensations (dysesthesia) in 12.5% against 0.9%, and 11.3% stopping treatment because of adverse events against 4.9%. The retatrutide Phase 2 paper also reported dose-related increases in heart rate. Long-term safety data for retatrutide are still being collected.

What this means for buyers of research products

All the results above belong to the sponsors' own drugs, given under medical supervision in clinical trials; they are not results for any product sold in a store, including ours. Product pages in our store list each item's brand, strength and label photo. We do not give dosing, preparation or usage instructions, and nothing on this page is medical advice. For the full source-referenced summaries, see the Retatrutide and Tirzepatide monographs, or browse the Retatrutide and Tirzepatide categories.