Enicepatide (CT-388): Roche's Biased GLP-1/GIP Agonist
A once-weekly dual GLP-1/GIP agonist with strong early Phase 2 numbers. Here is what those numbers show, how they line up against tirzepatide, and which parts are still unpublished.
How It Works
CT-388 is a single peptide that activates both the GLP-1 and GIP receptors. That is the same receptor pair tirzepatide targets (PMID 41319798). Retatrutide adds a third target, the glucagon receptor (PMID 37366315).
In cell assays, CT-388 favored cAMP signaling and caused minimal receptor internalization at both receptors (PMID 41319798). Tirzepatide shows this bias only at the GLP-1 receptor and mimics native GIP at the GIP receptor (PMID 32730231).
In the peer-reviewed Phase 1 study, four weekly doses (5–12 mg) cut body weight by 4.7% to 8.0% at day 29, vs 0.5% on placebo. Pharmacokinetics supported once-weekly dosing (PMID 41319798).
In preclinical models, biased agonism gave more weight loss than unbiased agonism (PMID 41319798). No head-to-head human trial yet shows that this beats tirzepatide.
What the Data Shows
Where Do the Enicepatide Phase 2 Numbers Come From?
The headline Phase 2 figures are company-reported topline results, not yet a peer-reviewed paper. The only peer-reviewed human data on CT-388 so far is the 4-week Phase 1 study (PMID 41319798). Treat the Phase 2 numbers as provisional until the full trials are published.
At 24 mg: HbA1c down 2.65 points from a baseline of 8.1%. 90% reached HbA1c ≤6.5% and 62% reached HbA1c <5.7%. Mean weight loss was 15.5% with no plateau reported. Across all enicepatide arms combined (not 24 mg alone), 2.0% stopped for adverse events vs 0.0% on placebo.
Roche topline release, 22 Sep 2026 →At 24 mg: 22.5% placebo-adjusted weight loss (efficacy estimand), or 18.3% on the treatment-regimen estimand. Across all CT-388 dose arms combined (not 24 mg alone), 5.9% stopped for adverse events vs 1.3% on placebo.
Genentech topline release, 26 Jan 2026 →Key Takeaways
- Enicepatide is the name for CT-388, a once-weekly injectable dual GLP-1/GIP receptor agonist that Roche acquired with Carmot Therapeutics.
- In lab studies, it is cAMP-biased with minimal receptor internalization at both receptors. That design is meant to reduce receptor desensitization (PMID 41319798).
- In a peer-reviewed Phase 1 study, 4 weekly doses reduced body weight 4.7–8.0% at day 29, vs 0.5% on placebo, and were generally well tolerated (PMID 41319798).
- Roche reports that in type 2 diabetes, 24 mg lowered HbA1c 2.65 points and body weight 15.5% at 48 weeks, and 90% reached HbA1c ≤6.5%.
- In people without diabetes, Genentech reports 22.5% placebo-adjusted weight loss at 48 weeks on 24 mg (18.3% on the treatment-regimen estimand).
- As with other incretin drugs, the most common side effects reported were mild-to-moderate gastrointestinal events.
- Neither Phase 2 trial has been published in a peer-reviewed journal. Full results, including per-dose safety data, are not yet public.
- The 15.5% figure is mean loss, not placebo-adjusted, so it is not directly comparable to placebo-adjusted numbers.
- No head-to-head trial against tirzepatide, semaglutide or retatrutide exists. Every comparison on this page is cross-trial.
- It is still unknown whether dual biased agonism gives a real clinical edge over tirzepatide in humans.
- Long-term safety, weight regain after stopping, and cardiovascular outcomes are unknown until the Phase 3 program reads out.
Frequently Asked Questions
What is enicepatide (CT-388)?
Enicepatide is the name for CT-388, an investigational once-weekly injectable that activates both the GLP-1 and GIP receptors. Carmot Therapeutics originally developed it, and it is now in development at Roche/Genentech. It is designed to be signal-biased, favoring cAMP signaling with minimal receptor internalization at both receptors (PMID 41319798). A 2021 review of GLP-1-based obesity drugs already listed it as being in clinical development (PMID 34176426). It is not approved anywhere.
How much weight did people lose on enicepatide in Phase 2?
Two company topline releases give the figures, and neither is peer-reviewed yet. In adults with type 2 diabetes (CT-388-104), the 24 mg dose gave 15.5% mean weight loss at 48 weeks. In adults with obesity and no diabetes (CT388-103), Genentech reported 22.5% placebo-adjusted weight loss at 48 weeks on 24 mg, or 18.3% on the treatment-regimen estimand.
Is enicepatide better than tirzepatide?
Nobody knows yet, because there is no head-to-head trial. In type 2 diabetes, enicepatide reported 15.5% mean weight loss at 48 weeks. In SURMOUNT-2, tirzepatide 15 mg gave 14.7% at 72 weeks (PMID 37385275). These are different trials with different lengths, and the enicepatide data is still unpublished. Both drugs target the same two receptors; enicepatide differs in being biased at both.
Why is weight loss lower in the type 2 diabetes trial?
People with type 2 diabetes usually lose less weight on incretin drugs than people without diabetes. Tirzepatide 15 mg shows the same pattern: 20.9% mean weight loss without diabetes in SURMOUNT-1 (PMID 35658024) vs 14.7% with diabetes in SURMOUNT-2 (PMID 37385275). So the 15.5% enicepatide figure should be compared with diabetes trials, not obesity-only trials.
When could enicepatide be available?
Not soon. Roche says two Phase 3 weight-management trials (ENITH-1 and ENITH-2) are underway. It plans to start a Phase 3 glycemic-control program and cardiovascular outcomes trials in the first half of 2027. Enicepatide is not FDA-approved, and this page is educational information, not medical advice.
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Educational purposes only. Not medical advice.
Enicepatide (CT-388) is an investigational drug. It is not FDA-approved and is not available as a prescription or research product. Phase 2 figures on this page are company-reported topline results, not peer-reviewed data.
Always consult a qualified healthcare provider before starting, stopping, or changing any medication.