Retatrutide vs Mounjaro: what the trials of the two Lilly peptides show

Photograph: editorial illustration for this article. It does not show retatrutide.

What is each drug?

Mounjaro is the brand name of tirzepatide for type 2 diabetes; Zepbound is the same molecule approved for weight management. Tirzepatide is a 39-amino-acid peptide that activates two receptors, GIP and GLP-1, injected once a week. It was approved by the FDA for diabetes in May 2022 and for obesity in November 2023.

Retatrutide is Lilly's next molecule. It is also a 39-amino-acid weekly peptide, also built on a GIP backbone, but engineered to activate a third receptor, glucagon, in addition to GIP and GLP-1^[8]. It is investigational: no regulator has approved it, and Lilly plans an FDA filing in the first quarter of 2027^[7]. Our mechanism article explains what the glucagon receptor adds.

How does weight loss compare?

The pivotal tirzepatide obesity trial, SURMOUNT-1, randomised 2,539 adults without diabetes and reported mean weight change at 72 weeks of −15.0% on 5 mg, −19.5% on 10 mg and −20.9% on 15 mg, against −3.1% on placebo^[1]. The corresponding retatrutide trial, TRIUMPH-1, randomised 2,339 adults and reported −19.0% on 4 mg, −25.9% on 9 mg and −28.3% on 12 mg at 80 weeks, against −2.2% on placebo^[6].

Even the published phase 2 retatrutide data, at 48 weeks and in only 338 people, showed −24.2% on 12 mg^[4], already above tirzepatide's 72-week result. The direction of the difference is consistent across every data set. Its exact size is not known, because the trials differ in length (72 versus 80 weeks), in baseline weight, in escalation schedules and in the year they were run.

How do they compare on blood sugar?

Tirzepatide has a large diabetes evidence base. In SURPASS-2, 40 weeks against semaglutide 1 mg, HbA1c fell by 2.01, 2.24 and 2.30 percentage points on 5, 10 and 15 mg, against 1.86 on semaglutide^[3]. In SURMOUNT-2, people with type 2 diabetes and obesity lost 12.8% (10 mg) and 14.7% (15 mg) at 72 weeks against 3.2% on placebo^[2].

Retatrutide's phase 2 diabetes trial reported HbA1c reductions of about two percentage points at 24 weeks on the 8 mg and 12 mg doses, against 1.41 on dulaglutide 1.5 mg, and weight change of −16.94% on 12 mg at 36 weeks^[5]. TRIUMPH-2 then reported −20.8% weight change at 80 weeks on 12 mg and HbA1c reductions of 1.4 to 1.6 points from a 7.7% baseline^[7]. On glucose the two drugs look broadly similar; on weight in people with diabetes, retatrutide's 80-week number is higher than tirzepatide's 72-week number, with the same cross-trial caveats. Details are in retatrutide for type 2 diabetes.

How do side effects compare?

Both drugs are dominated by gastrointestinal effects during dose escalation. In SURMOUNT-1, nausea affected 24.6% to 33.3% of tirzepatide participants depending on dose, and 6.2% of the 15 mg group discontinued for adverse events versus 2.6% on placebo^[1]. In TRIUMPH-1, nausea affected 28.6%, 38.4% and 42.4% of the 4, 9 and 12 mg groups versus 14.8% on placebo, and 11.3% of the 12 mg group discontinued for adverse events versus 4.9% on placebo^[6].

The glucagon component brings one effect tirzepatide does not have to the same degree: a dose-dependent rise in resting heart rate, which in the phase 2 obesity trial peaked around week 24 and then declined^[4]. The cardiovascular outcomes trial that will settle whether this matters clinically runs to 2029. The full picture is in GLP-3 side effects.

Which one can you actually get?

Only tirzepatide. Mounjaro and Zepbound are prescription medicines with an approved label, pharmacy supply and a defined dose-escalation schedule. Retatrutide is available only inside clinical trials or, in the United States, through a pre-approval expanded access program listed on ClinicalTrials.gov. Anything else sold under its name is an unapproved product, as discussed in the retatrutide grey market.

What can the comparison say, and what can it not?

• It can say that in every trial so far, retatrutide's top dose produced more mean weight loss than tirzepatide's top dose in a comparable population.
• It can say that both drugs lower HbA1c by roughly two percentage points in people with type 2 diabetes.
• It can say that retatrutide's discontinuation rate for adverse events at the top dose is about twice that of tirzepatide's in the respective pivotal trials.
• It cannot say how much of the difference would survive a head-to-head trial with matched duration and escalation, because none has been published.
• It cannot say anything about long-term safety of retatrutide beyond 104 weeks, since that is the longest follow-up announced.