Tirzepatide vs Retatrutide: What the Trials Show About Weight Loss, Side Effects and Approval Status

Tirzepatide vs retatrutide is a comparison many people on GLP-1 therapy now ask about. Tirzepatide has been FDA approved for chronic weight management since 2023, while retatrutide, also developed by Eli Lilly, published its first phase 3 results in the autumn of 2026 with larger average weight loss than the tirzepatide trials reported.

Those numbers come from separate trials, however, and retatrutide is not approved, so this guide sets out what each trial measured and where the two medicines differ.

What is the difference between tirzepatide and retatrutide?

The core difference is the number of hormone receptors each medicine activates. Tirzepatide activates the GIP and GLP-1 receptors, and retatrutide activates both of those plus the glucagon receptor, which is why researchers describe it as a triple agonist (Jastreboff et al., New England Journal of Medicine, 2026).

GIP and GLP-1 signaling act mainly on appetite, fullness and insulin release, as explained in our guide to how tirzepatide works as a dual agonist. Glucagon influences how the liver handles fat and energy, and the idea behind adding it is that it may raise energy use, although the published trials measured outcomes rather than mechanism. Both medicines are weekly injections started at a low dose and stepped up over time.

How much weight did people lose on retatrutide in phase 3?

In TRIUMPH-1, the first phase 3 retatrutide trial in obesity, people lost an average of 17.6% to 25.0% of their body weight over 80 weeks, depending on dose. The trial randomized 2339 adults with obesity and no diabetes to weekly retatrutide 4 mg, 9 mg or 12 mg, or placebo, and average weight loss was 17.6%, 23.7% and 25.0% on the three doses compared with 3.9% on placebo. These figures count everyone who was randomized, including people who stopped the medicine.

In TRIUMPH-1 substudies, among 574 participants with knee osteoarthritis, WOMAC pain scores fell by 3.2, 3.5 and 3.6 points on the three doses, versus 1.9 points on placebo. Among 243 participants with obstructive sleep apnea, the apnea hypopnea index fell by 22.8, 34.3 and 32.1 events per hour, versus 9.6 on placebo.

A 48 week phase 2 trial of 338 adults pointed the same way earlier (Jastreboff et al., New England Journal of Medicine, 2023). Average weight loss at 48 weeks was 8.7% on 1 mg, 17.1% on 4 mg, 22.8% on 8 mg and 24.2% on 12 mg, compared with 2.1% on placebo.

How does that compare with tirzepatide's weight loss results?

Tirzepatide's main obesity trial, SURMOUNT-1, produced average weight loss of 15.0%, 19.5% and 20.9% on the 5 mg, 10 mg and 15 mg doses over 72 weeks, compared with 3.1% on placebo (Jastreboff et al., New England Journal of Medicine, 2022). The trial enrolled 2539 adults without diabetes, and at the two higher doses 50% and 57% of participants lost 20% or more of their body weight, against 3% on placebo.

The retatrutide trial therefore showed more average weight loss, but that does not prove retatrutide works better. No published trial has randomized people to one medicine or the other, TRIUMPH-1 ran eight weeks longer while weight was still falling, and the placebo groups differed (3.9% and 3.1%), which suggests the trial settings were not identical. A fair answer needs a dedicated head to head trial, like the one in our tirzepatide vs semaglutide guide.

What happened in people with type 2 diabetes?

In people with type 2 diabetes, both medicines produced less weight loss than in people without diabetes, a pattern seen across this drug class. TRIUMPH-2 randomized 1152 adults with obesity and type 2 diabetes, with a mean BMI of 38.2 and a mean HbA1c of 7.71%, to retatrutide 4 mg, 9 mg or 12 mg, or placebo, for 80 weeks (Bellido et al., Lancet, 2026). Average weight loss was 11.9%, 16.8% and 18.8% on the three doses, compared with 5.1% on placebo.

Tirzepatide's equivalent trial, SURMOUNT-2, randomized 938 adults with obesity and type 2 diabetes and a mean HbA1c of 8.02% to tirzepatide 10 mg or 15 mg, or placebo, for 72 weeks (Garvey et al., Lancet, 2023). Average weight loss was 12.8% and 14.7%, compared with 3.2% on placebo. Our article on tirzepatide with type 2 diabetes explains why.

Are the side effects of retatrutide different from tirzepatide?

Retatrutide's side effects overlap heavily with tirzepatide's, although TRIUMPH-2 also reported some less familiar ones.

Gastrointestinal effects. In TRIUMPH-2, diarrhea occurred in 27%, 34% and 34% of people on retatrutide 4 mg, 9 mg and 12 mg, versus 13% on placebo, and nausea occurred in 14%, 21% and 28%, versus 8%. Tirzepatide's most common side effects in SURMOUNT-1 were also gastrointestinal, mostly mild to moderate.

Dysesthesia. Dysesthesia, meaning abnormal skin sensations such as tingling or burning, was reported in 4%, 6% and 7% of people on the three retatrutide doses, versus 1% on placebo.

Low blood pressure and heart rate. Hypotension was reported in 1%, 5% and 6% of people on the three retatrutide doses in TRIUMPH-2, versus under 1% on placebo. In the phase 2 trial, heart rate rose in a dose dependent way, peaked at 24 weeks and declined afterward, and gastrointestinal events were partly reduced by starting at 2 mg rather than 4 mg.

Stopping because of side effects. In TRIUMPH-2, permanent discontinuation due to adverse events or death occurred in 12% of the 9 mg group and 8% of the 12 mg group, compared with 4% on 4 mg and 5% on placebo. In SURMOUNT-1, adverse events led to discontinuation in 4.3%, 7.1% and 6.2% of people on tirzepatide 5 mg, 10 mg and 15 mg, compared with 2.6% on placebo.

Serious warnings. The Zepbound label carries a boxed warning because tirzepatide caused thyroid C-cell tumors in rats, and it should not be used by people with a personal or family history of medullary thyroid carcinoma or with Multiple Endocrine Neoplasia syndrome type 2 (Zepbound prescribing information). The label also warns about pancreatitis, acute gallbladder disease, low blood sugar when combined with insulin or insulin secretagogues, and possible fetal harm in pregnancy. Retatrutide acts on the same receptors and more, and whether it shares these class concerns over the longer term has not yet been established.

Is retatrutide FDA approved?

Retatrutide is not FDA approved for any use, and it remains under investigation for obesity and several related conditions. Tirzepatide, by contrast, was approved as Zepbound for chronic weight management on November 8, 2023, for adults with a BMI of 30 or higher, or 27 or higher with at least one weight related condition, after it had already been approved as Mounjaro for type 2 diabetes (FDA, 2023).

The FDA's page on unapproved GLP-1 drugs states that retatrutide cannot be used in compounding under federal law and lists warning letters sent to telehealth companies, ingredient distributors and outsourcing facilities over retatrutide (FDA, 2026). The content and purity of products labeled for research use cannot be verified.

Should someone switch from tirzepatide to retatrutide?

Switching is not currently possible through legitimate medical care in the United States, because retatrutide is not approved and cannot be compounded. When progress on tirzepatide is slow, our guide to slow progress on tirzepatide covers common reasons, and a licensed clinician can review whether a dose change or another option makes sense. The FDA approval of Zepbound and Mounjaro applies to those branded products only.

What is still unknown about retatrutide?

No head to head trial against tirzepatide has been published, the phase 3 trials ran for 80 weeks so longer term safety is not yet known, and no data on weight change after stopping retatrutide has been published. The tirzepatide picture after stopping is covered in our guide to weight regain after stopping GLP-1 therapy.

The bottom line

Retatrutide showed larger average weight loss in its phase 3 trials than tirzepatide did in its own, but those are separate trials rather than a direct contest. It also brought less familiar side effects such as dysesthesia and low blood pressure, and it is not FDA approved, so branded tirzepatide (Zepbound, Mounjaro) remains the FDA approved option with years of prescribing experience behind it. Individual results with either medicine vary.