Roche's enicepatide posts 22.5% placebo-adjusted weight loss and heads to Phase 3

Roche said on January 27 that its dual GLP-1/GIP receptor agonist, CT-388, produced 22.5% placebo-adjusted weight loss at 48 weeks in a Phase 2 obesity trial, and that the company will start two Phase 3 studies this quarter ^[1]. The drug came to Roche through its $2.7 billion buyout of Carmot Therapeutics in 2023 ^[1][2].

What the trial showed

The study tested three subcutaneous doses of CT-388 against placebo in 469 people with obesity or who were overweight ^[1]. The shot is given once weekly ^[2]. The main measure was percent change in placebo-adjusted body weight from the start of the study to Week 48, and the highest dose tested — 24 mg — hit 22.5% ^[1].

Roche also reported a second way of counting the same result. Using what statisticians call the treatment-regimen estimand, which includes people regardless of whether they stopped the drug, placebo-adjusted weight loss was 18.3% ^[1]. Both numbers come from the same trial; the lower one is generally the more conservative view.

At the top dose, 95.7% of participants lost more than 5% of their body weight and 26.1% lost more than 30% ^[1]. More than half of participants achieved what Roche called resolution of obesity, versus 13% on placebo, and 73% of those who entered with prediabetes had normal blood sugar at Week 48, compared with 7.5% in the placebo group ^[2]. Roche said weight loss had not plateaued by Week 48 ^[1][2].

On safety, Roche described CT-388 as well tolerated, with the "majority of gastrointestinal-related adverse events being mild-to-moderate, generally consistent with the incretin class of medicines" ^[1]. Treatment discontinuation was 5.9% in the CT-388 arms versus 1.3% on placebo ^[1][2]. Roche did not release details of why people dropped out and is holding the full dataset for a future medical meeting ^[1][2].

How it stacks up

The obvious comparison is Eli Lilly's tirzepatide (Zepbound), also a GLP-1/GIP dual agonist. Zepbound's US prescribing information ties the 15 mg dose to a 20.9% reduction in body weight after 36 weeks ^[1]. Analysts at William Blair called CT-388 comparable to Zepbound, and noted that Zepbound added roughly another 2% weight loss between Week 48 and Week 72 — meaning CT-388's numbers could still move in later readouts ^[2].

Lilly's retatrutide, a triple-hormone agonist, cut body weight by 26.6% on a placebo-adjusted basis at 68 weeks ^[2]. Analysts at ODDO BHF called the Roche data a "material pipeline upgrade" and said "the combination of depth of response, absence of an early plateau and acceptable tolerability suggests CT-388 could sit in the top efficacy tier if replicated in phase 3" ^[1]. William Blair put CT-388 about a year behind Viking Therapeutics' VK2735 ^[2].

Why it matters for patients

Nothing changes today for anyone taking semaglutide (Ozempic, Wegovy, Rybelsus) or tirzepatide (Mounjaro, Zepbound). CT-388 is an experimental drug that has only completed mid-stage testing. Morningstar does not expect a launch until 2029 ^[2].

What the result signals is that the competitive field behind the two current leaders is real and getting deeper. Roche laid out a strategy in September 2025 to become a "top three" obesity company, partly by combining drugs from across its portfolio ^[1]. More approved options over time can mean more choice on formularies and more pressure on pricing, though none of that is guaranteed and the sources do not address US coverage or cost for CT-388.

One specific thread worth watching is tolerability. Roche plans to pair CT-388 with petrelintide, a long-acting amylin analog it is codeveloping with Zealand Pharma under a $1.6 billion upfront deal, specifically to address nausea — the main driver of people quitting current weight-loss drugs ^[1][2]. The stated aim is weight loss without the gastrointestinal side effects that many GLP-1 users know well ^[2].

What happens next

• This quarter: Roche starts two Phase 3 obesity trials of CT-388 ^[1].
• First half of 2026: Roche and Zealand are expected to begin a combination study of CT-388 plus petrelintide ^[2].
• Date not yet announced: full Phase 2 data, including dropout details, at a medical conference ^[1][2].

Separately, Roche paid $100 million to Structure Therapeutics earlier in January for a nonexclusive patent license tied to CT-996, an oral GLP-1 that also came from Carmot ^[1].