What Is Enicepatide?

1. Where Did Enicepatide Come From?

Enicepatide was not developed in-house at Roche. It was the lead asset of Carmot Therapeutics, a California biotech, under the code CT-388. Roche agreed to buy Carmot on December 4, 2023 for $2.7 billion upfront plus up to $400 million in milestones, picking up two other incretin candidates and a discovery platform in the same deal (acquisition announcement). Roche then labelled it a fast-track asset and compressed the usual development calendar: Phase 2 read out in January 2026 and Phase 3 started two months later (Phase 2 announcement).

That history explains the three names. CT-388 is Carmot’s code and still appears on trial registries. RO7795068 is Roche’s internal code. Enicepatide is the generic name Roche adopted in 2026. ENITH is the name of the Phase 3 program, not a brand (ENITH-1 registry).

2. How Does Enicepatide Work?

Enicepatide is a peptide given by weekly injection under the skin. It activates the GLP-1 and GIP receptors, the same pair targeted by tirzepatide, with the aim of reducing appetite and improving blood-sugar control (Roche mechanism overview). It is a separate molecule from tirzepatide despite sharing the receptor class.

What Roche says makes it different is how it activates those receptors. It was designed for strong cAMP signaling with minimal to no beta-arrestin recruitment, which the company describes as signal-biased agonism. A peer-reviewed Molecular Metabolism paper reported that this design limits receptor internalization in laboratory experiments, meaning the receptor stays on the cell surface rather than being pulled inside after activation. The hypothesis is that this sustains the drug’s effect. A laboratory mechanism does not by itself prove better clinical results, so the trial data below carry more weight than the design story.

3. What Did the Early Phase 1b Study Show?

Before the Phase 2 program, Roche reported a 24-week Phase 1b cohort in otherwise healthy adults with obesity. Weekly CT-388 produced a mean placebo-adjusted weight loss of 18.8%. Every treated participant lost more than 5% of body weight, 70% lost more than 15%, and 45% lost more than 20%. All participants who started with prediabetes had normal blood glucose by week 24 (May 2024 Phase 1b results).

Those figures came from a small, short study in people without diabetes, so they served to justify Phase 2 rather than to predict what a broad population would see. They do show why Roche paid what it paid.

4. What Did the Phase 2 Trial Show?

CT388-103, registered as NCT06525935, was a randomized, double-blind, placebo-controlled dose-finding trial in 469 adults without type 2 diabetes who had obesity, or overweight with at least one weight-related condition. Five active cohorts used different dose-escalation schedules, with 24 mg the highest target dose. The primary outcome was percentage change in body weight at 48 weeks (January 2026 announcement).

The efficacy estimand estimates results under treatment-adherence assumptions; the treatment-regimen estimand accounts for discontinuation and related events. “Placebo-adjusted” is the difference between groups. Two further details from Roche’s announcement matter more than the headline:

• Weight loss had not plateaued at 48 weeks. The curve was still falling when the trial ended. The Phase 3 trials measure their primary outcome at 72 weeks instead (ENITH-1 registry).
• The response was broad, not driven by a few outliers. At 24 mg, 95.7% of participants lost at least 5%, 87% lost at least 10%, 47.8% lost at least 20%, and 26.1% lost at least 30%. More than half, 54%, finished below a BMI of 30, compared with 13% on placebo. Among those with prediabetes at the start, 73% had normal blood glucose at week 48 versus 7.5% on placebo (Phase 2 announcement).

Roche also described a clear dose-response relationship across the five cohorts, which supports the idea that the effect is real rather than a quirk of one arm.

5. What Side Effects Were Reported?

Roche’s Phase 2 announcement reported mainly mild-to-moderate gastrointestinal adverse events, the pattern expected for the incretin class. Treatment discontinuation because of adverse events occurred in 5.9% across CT-388 arms versus 1.3% with placebo. The active-treatment figure is pooled across doses; it is not a side-effect rate specific to the highest-dose group (January safety summary).

The full ADA presentation gave per-dose rates. Gastrointestinal side effects rose with dose: at 24 mg, 46% of participants reported nausea, 32% diarrhea, 24% constipation and 21% vomiting, against 19%, 10%, 8% and 0% on placebo. Serious adverse events occurred in 5% of the 24 mg group and none of the placebo group (Roche ADA presentation).

Roche describes the 5.9% discontinuation rate as low, but there is no head-to-head comparison with other drugs, and the per-dose figures show nausea and vomiting were common at the top dose. Whether that holds in a larger and less selected Phase 3 population is one of the main open questions.

6. Phase 3 Trials and Approval Timeline

The two pivotal studies separate participants by diabetes status:

A third, smaller Phase 3 trial (NCT07670416) began on July 3, 2026 in about 300 Chinese adults with obesity or overweight, with or without type 2 diabetes. Its primary outcome is weight change at 52 weeks, with estimated primary completion on February 24, 2028.

Phase 2 results in type 2 diabetes

A separate Phase 2 study, CT-388-104 (NCT06628362), tested enicepatide in 447 adults with obesity or overweight who also have type 2 diabetes. Roche reported topline results on September 22, 2026. At 48 weeks, the 24 mg group’s HbA1c fell by 2.65 percentage points from a baseline of 8.1%, 90% of that group reached an HbA1c of 6.5% or lower, and 62% reached under 5.7%. Mean weight loss in that group was 15.5%, again without a clear plateau. Treatment discontinuation because of adverse events was 2.0% across enicepatide arms versus 0.0% on placebo. These are changes from baseline in a topline press release; placebo-adjusted differences and full data have not yet been published. Roche plans to start a Phase 3 glycemic-control program and cardiovascular outcomes trials in the first half of 2027 (September 2026 announcement).

There is no confirmed enicepatide release date as of October 15, 2026. Roche places a potential regulatory submission in 2028 in its April pipeline presentation, and kept that timing in its July half-year presentation. That is a company forecast, conditional on development progress, rather than a regulator’s approval deadline (Roche pipeline presentation, April 2026; Roche half-year presentation, July 2026).

7. How Does It Compare With Other Compounds?

Enicepatide’s Phase 2 trial used placebo; it did not directly compare enicepatide with semaglutide, tirzepatide, or other GLP-1/GIP dual agonists in late-stage trials such as ribupatide and VK2735 (VANQUISH 1 registry). Separate trial results cannot establish which drug works better, because populations, durations and analysis methods differ.

Roche’s own framing is that enicepatide matters as much for what it can be combined with as for what it does alone. Petrelintide, the amylin analog Roche is developing in partnership with Zealand Pharma, was designed to be co-formulated with other peptides. Roche’s multi-arm Phase 2 trial pairing the two, ZYNERGY (NCT07589686), plans about 486 participants with a 40-week primary endpoint; as of its September 2026 registry update it was not yet recruiting, with an estimated start of September 30, 2026. The rationale is that amylin and incretin drugs reduce appetite through different pathways, so a combination might add weight loss or allow lower doses of each (Roche portfolio update). That combination is a separate program with its own timeline, and none of its results exist yet.

8. Enicepatide FAQ

• Is enicepatide the same as CT-388?

  Yes. CT-388 was Carmot Therapeutics' code, RO7795068 is Roche's internal code, and enicepatide is the generic name adopted in 2026. Registry entries and older papers still use CT-388.

• When will enicepatide be available?

  There is no confirmed launch date. Roche lists a 2028 submission target, followed by regulatory review if the application proceeds. The two main Phase 3 trials are not due to report their main results until mid-2028; a smaller Phase 3 trial in China has an estimated primary completion in February 2028.

• How much weight loss did CT-388 produce?

  At 48 weeks, the highest-dose Phase 2 group had 22.7% mean weight loss versus 0.2% with placebo under the efficacy estimand. Counting people who stopped treatment, the placebo-adjusted figure was 18.3 percentage points. Roughly one in four participants on 24 mg lost 30% or more.

• Does enicepatide help blood sugar?

  In the Phase 2 trial, 73% of participants who started with prediabetes had normal blood glucose at week 48, against 7.5% on placebo. In a separate Phase 2 study, CT-388-104, in people who already had type 2 diabetes, the 24 mg dose lowered HbA1c by 2.65 percentage points from a baseline of 8.1% at 48 weeks, and 90% of that group reached an HbA1c of 6.5% or lower. Roche reported these as changes from baseline, not placebo-adjusted figures. The Phase 3 ENITH-2 trial is now testing it in this population.

• Is enicepatide better than tirzepatide?

  Unknown. The Phase 2 study compared enicepatide with placebo, not tirzepatide, and no head-to-head trial has been announced. Both are weekly GLP-1/GIP injections, so any advantage would have to come from differences such as Roche's signal-biased design, tolerability or the combination plans, not the receptor targets. None of these has been shown in a head-to-head trial.

9. Sources