Tirzepatide and retatrutide are both Eli Lilly incretin peptides, but they are not the same drug class. Tirzepatide is a dual GIP/GLP-1 receptor agonist with completed phase 3 obesity and diabetes programs. Retatrutide (LY3437943) adds glucagon-receptor agonism and, as of the sources below, has published phase 1 and phase 2 data only.
This page is for laboratory and literature comparison. It is not medical advice, not a treatment guide, and not a protocol. Approved-drug facts refer to FDA-labeled products, not to research vials.
Research notice: Compounds discussed for research use are not approved for human consumption, medical treatment, or diagnosis. Follow institutional and legal rules. FDA-approved medicines (Mounjaro, Zepbound) are separate from research-grade material.
| Parameter | Tirzepatide | Retatrutide |
|---|---|---|
| Developmental name | LY3298176 | LY3437943 |
| Receptor targets | GIP receptor and GLP-1 receptor | GIP, GLP-1, and glucagon receptors |
| Sponsor | Eli Lilly | Eli Lilly |
| US FDA status | Approved: Mounjaro (type 2 diabetes, May 13, 2022); Zepbound (chronic weight management, November 8, 2023) | Not approved; investigational |
| Largest published obesity trial cited here | SURMOUNT-1, phase 3, 2539 adults, 72 weeks | Phase 2, 338 adults, 48 weeks |
| Published mean weight change (separate trials) | -15.0%, -19.5%, -20.9% at 72 weeks (5, 10, 15 mg vs placebo -3.1%) | -24.2% at 48 weeks (12 mg vs placebo -2.1%) |
| Direct human head-to-head | None versus retatrutide | None versus tirzepatide |
Those weight figures are from different protocols, durations, and populations. They are not a substitute for a comparative trial.
Tirzepatide is a dual agonist at the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor. Coskun and colleagues described LY3298176 as a dual GIP/GLP-1 agonist from discovery through early clinical proof of concept. Willard and colleagues later reported that tirzepatide is imbalanced toward the GIP receptor relative to the GLP-1 receptor and is biased at GLP-1 toward cAMP generation over beta-arrestin recruitment.
Retatrutide is a single acylated peptide with agonist activity at the glucagon receptor (GCGR), GIP receptor, and GLP-1 receptor. Coskun and colleagues reported that LY3437943 showed balanced GCGR and GLP-1R activity in vitro but greater GIPR activity. In obese mice, body-weight loss was larger than with tirzepatide, and glucagon-receptor activity increased energy expenditure on top of reduced calorie intake from GIPR and GLP-1R. A first-in-human single-ascending-dose study supported once-weekly pharmacokinetics, with body-weight reduction persisting to day 43 after a single dose.
The extra receptor is the actual comparison, not a marketing add-on. GLP-1 agonism is shared. GIP agonism is shared. Glucagon-receptor activity is the retatrutide-only limb in this pair.
Tirzepatide is an approved US drug:
Retatrutide is not FDA-approved. Jastreboff et al. (2023) is a phase 2 obesity trial (NCT04881760). Rosenstock et al. (2023) is a phase 2 type 2 diabetes trial (NCT04867785) that the authors said informed dose selection for phase 3. Those are development facts, not an approval timeline. Do not treat estimated launch years as data.
Research-grade tirzepatide or retatrutide sold as laboratory chemicals is not Mounjaro, Zepbound, or a licensed investigational product.
Jastreboff et al. randomly assigned 2539 adults with obesity, or overweight plus a weight-related complication, without diabetes, to once-weekly subcutaneous tirzepatide 5, 10, or 15 mg or placebo for 72 weeks. Mean percentage weight change at week 72 was -15.0% (5 mg), -19.5% (10 mg), and -20.9% (15 mg) versus -3.1% with placebo. A 20% or greater weight reduction occurred in 50% (10 mg) and 57% (15 mg) versus 3% with placebo. Gastrointestinal adverse events were the most common, mostly mild to moderate, mainly during dose escalation. Treatment discontinuation due to adverse events was 4.3%, 7.1%, 6.2%, and 2.6% for 5 mg, 10 mg, 15 mg, and placebo.
Jastreboff, Kaplan, Frias et al. enrolled 338 adults in a 48-week, placebo-controlled phase 2 trial of once-weekly subcutaneous retatrutide. The primary end point was percentage weight change at 24 weeks; 48-week change was secondary. At 48 weeks, least-squares mean percentage weight change was -8.7% (1 mg), -17.1% (combined 4 mg), -22.8% (combined 8 mg), and -24.2% (12 mg) versus -2.1% with placebo. Gastrointestinal events were dose-related and mostly mild to moderate; a lower starting dose (2 mg versus 4 mg) partly reduced them. Dose-dependent heart-rate increases peaked at 24 weeks and declined thereafter.
Rosenstock et al. assigned 281 adults with type 2 diabetes in the US to placebo, dulaglutide 1.5 mg, or retatrutide maintenance doses including 12 mg, once weekly. At 24 weeks, HbA1c change with retatrutide 12 mg was -2.02% versus -0.01% placebo and -1.41% dulaglutide. At 36 weeks, body weight fell 16.94% with retatrutide 12 mg versus 3.00% placebo and 2.02% dulaglutide. Mild-to-moderate gastrointestinal events occurred in 35% of retatrutide-treated participants overall (13% at 0.5 mg to 50% in the 8 mg fast-escalation group), 13% with placebo, and 35% with dulaglutide. No severe hypoglycemia and no deaths were reported.
There is no published human RCT that assigns tirzepatide versus retatrutide. SURMOUNT-1 is 72 weeks in people without diabetes. The retatrutide obesity trial is 48 weeks and phase 2 (n=338). Comparing -20.9% at 72 weeks with -24.2% at 48 weeks is not a head-to-head result.
Tirzepatide versus semaglutide does have a head-to-head obesity trial (SURMOUNT-5: -20.2% versus -13.7% at 72 weeks). That pair is a different page: Semaglutide vs Tirzepatide.
| Question | Tirzepatide | Retatrutide |
|---|---|---|
| Extra receptor versus GLP-1 alone | GIP | GIP plus glucagon |
| Human evidence maturity | Phase 3 obesity and diabetes; FDA-approved products | Phase 1/2 published; phase 3 not in the sources above as completed outcome papers |
| Obesity trial duration in the papers cited | 72 weeks | 48 weeks |
| Heart rate | Not the SURMOUNT-1 primary safety story in the abstract | Dose-dependent increases, peak at week 24, then decline |
| Energy expenditure mechanism (preclinical) | Dual incretin | Dual incretin plus GCGR-driven energy expenditure in mice |
| Research-use framing | Approved drug product exists; lab vials are still research chemicals | Investigational peptide only |
If the research question is dual versus triple agonism, retatrutide is the triple agonist with published phase 2 weight and HbA1c data. If the question is what has already been tested at phase 3 and licensed, tirzepatide is the one with FDA-approved products.
Related comparisons: Semaglutide vs Tirzepatide, Semaglutide vs Retatrutide. Guide: Tirzepatide research guide.
No. Retatrutide (LY3437943) remains investigational. Published human data are phase 1 and phase 2. Tirzepatide is FDA-approved as Mounjaro for type 2 diabetes (May 13, 2022) and as Zepbound for chronic weight management (November 8, 2023).
No published phase 2 or phase 3 trial has randomized humans to tirzepatide versus retatrutide. Weight-loss figures come from separate programs (SURMOUNT-1 for tirzepatide; a 48-week phase 2 trial for retatrutide) and cannot be treated as a direct ranking.
Tirzepatide is a dual agonist at the GIP and GLP-1 receptors. Retatrutide is a single peptide agonist at the GIP, GLP-1, and glucagon receptors. In mice, glucagon-receptor activity added energy-expenditure effects on top of reduced calorie intake.
Neither compound has a completed cardiovascular-outcome trial comparable to SELECT for semaglutide. Do not infer MACE benefit for tirzepatide or retatrutide from weight-loss trials alone.
No. FDA-approved tirzepatide products are prescription medicines. Research-grade listings on this site are not approved drugs. This page is informational and is not medical advice.
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