Metabolic/Weight

Enicepatide

Research Reagent · Laboratory Use Only

Quick Answer

What does research show about enicepatide (CT-388) for obesity?

Enicepatide (CT-388) is Roche/Genentech's once-weekly, signaling-biased dual GLP-1/GIP receptor agonist peptide, originally developed by Carmot Therapeutics. A Phase 1 trial published in Molecular Metabolism (2025) showed up to 8.0% weight loss at 4 weeks. Phase 2 topline data presented at ADA 2026 showed 22.5% placebo-adjusted weight loss at 48 weeks at the highest dose, with 54% of participants achieving BMI under 30. It remains investigational, with Phase 2 trials ongoing in obesity and type 2 diabetes.

PMID41319798↗DOI10.1016/j.molmet.2025.102291↗⟳ Reconstitution Calculator
Scientific AbstractPMID 41319798 · 2025

Enicepatide (CT-388, RO7795068) is a unimolecular, once-weekly, cAMP signal-biased dual GLP-1 receptor/GIP receptor (GLP-1R/GIPR) agonist originally developed by Carmot Therapeutics and advanced by Roche/Genentech following Roche's 2023 acquisition of Carmot. Biased agonism minimizes receptor internalization relative to native ligands, a design intended to sustain signaling and improve efficacy. 5 mg) or four once-weekly doses (5-12 mg) of subcutaneous CT-388 in otherwise healthy participants with overweight or obesity, the drug was generally well tolerated with a safety profile consistent with other incretin-based therapies; most treatment-emergent adverse events were mild or moderate.

5% with placebo. 5% placebo-adjusted weight loss at 48 weeks, with 54% of participants achieving resolution of obesity (BMI <30 kg/m²) versus 13% on placebo, and no plateau in weight loss observed. A full peer-reviewed publication of the Phase 2 efficacy data was not yet available as of this entry; Phase 2 studies are also underway in participants with obesity/overweight and type 2 diabetes.

Source:10.1016/j.molmet.2025.102291
Mechanistic Research SummaryCurated from PubMed

This data is for laboratory research purposes only. Not for human or animal consumption.

What is Enicepatide?

Enicepatide (development codes CT-388, RO7795068) is a once-weekly, signaling-biased dual GLP-1R/GIPR agonist peptide originally developed by Carmot Therapeutics and now advanced by Roche/Genentech. It is distinct from unbiased dual agonists (e.g., tirzepatide) in that it is engineered for cAMP signal bias with minimal receptor internalization at both the GLP-1 and GIP receptors — a design intended to preserve durable signaling and translate into greater weight loss.

Mechanism of Action

Enicepatide activates both the GLP-1 receptor and the GIP receptor with a cAMP-signaling bias and minimal receptor internalization relative to native incretin hormones. In preclinical models, this biased agonism improved glycemic control, reduced bodyweight, suppressed appetite, and improved metabolic dysfunction-associated steatohepatitis pathology, translating into clinically meaningful weight loss and glycemic improvement in early human studies.

Observed Clinical Results

  • Phase 1 trial (Molecular Metabolism, Nov 2025; PMID 41319798; NCT04838405): In otherwise healthy participants with overweight or obesity, single ascending doses (0.5-7.5 mg) or four once-weekly doses (5-12 mg) of CT-388 produced mean bodyweight change of -4.7% to -8.0% from baseline to day 29 versus -0.5% with placebo, with favorable tolerability and pharmacokinetics supporting once-weekly dosing.
  • Phase 2 obesity trial (NCT06525935): Topline results announced by Roche in January 2026 and presented in full at ADA 2026 — 22.5% placebo-adjusted weight loss at 48 weeks at the 24 mg dose, with 54% of participants achieving BMI <30 kg/m² versus 13% on placebo; no weight-loss plateau observed. Full peer-reviewed publication of this Phase 2 efficacy data was not yet available as of this entry.
  • Phase 2 type 2 diabetes trial (NCT06628362): Ongoing evaluation of enicepatide in adults with overweight/obesity and type 2 diabetes.

Regulatory Status

Investigational — no regulatory approval as of September 2026. Enicepatide is in Phase 2 clinical development for obesity and type 2 diabetes. Not eligible for 503A compounding as an investigational biologic peptide.

Clinical Research Parameters
3 trials1 human study

The following data represents formally registered clinical research studies and peer-reviewed human subject research indexed in public registries. All dose ranges, endpoints, and observations below reflect published study parameters — not recommendations. For research reference only.

Registered Clinical Trials
ClinicalTrials.gov ↗
NCT04838405 ↗
COMPLETEDPhase I

A Study of CT-388 in Healthy Participants With Overweight or Obesity

Phase 1, double-blind, randomised, placebo-controlled study of single ascending doses (0.5-7.5 mg) or four once-weekly doses (5-12 mg) of subcutaneous CT-388 (enicepatide) in otherwise healthy participants with overweight or obesity. CT-388 was generally well tolerated with a safety profile consistent with other incretin-based therapies. Mean bodyweight change from baseline to day 29 ranged from -4.7% to -8.0% across doses versus -0.5% with placebo; glycemic parameters improved during fasting and an oral glucose tolerance test. Published in Molecular Metabolism, November 2025 (PMID 41319798).

Study Interventions
CT-388 (enicepatide), Placebo
Primary Endpoints
Safety and tolerability; Pharmacokinetics; Percent change in bodyweight from baseline to day 29
Study Period
2021 → 2022
NCT06525935 ↗
ACTIVE NOT RECRUITINGPhase II

A Study of Enicepatide (CT-388) in Participants With Obesity or Overweight With at Least One Weight-Related Comorbidity

Randomised, double-blind, placebo-controlled, multicentre Phase 2 study (CT-388-103) evaluating the efficacy, safety, and tolerability of once-weekly subcutaneous enicepatide (CT-388) for 48 weeks in participants with obesity or overweight with at least one weight-related comorbidity. Roche announced positive topline results in January 2026, with full data presented at ADA 2026: at the highest 24 mg dose, enicepatide produced a statistically significant 22.5% placebo-adjusted weight loss at week 48, with 54% of participants achieving resolution of obesity (BMI <30 kg/m²) versus 13% on placebo and no weight-loss plateau observed. Safety and tolerability were generally consistent with the drug class, with no new or unexpected safety signals.

Study Interventions
Enicepatide (CT-388), Placebo
Primary Endpoints
Percent change in bodyweight from baseline at week 48; Safety and tolerability
Study Period
2024 → 2026
NCT06628362 ↗
RECRUITINGPhase II

A Study of Enicepatide (CT-388) in Participants Who Are Overweight or Obese With Type 2 Diabetes Mellitus

Phase 2 study evaluating the efficacy, safety, and tolerability of once-weekly subcutaneous enicepatide (CT-388) in adults with overweight or obesity and type 2 diabetes mellitus. Results not yet reported as of this update.

Study Interventions
Enicepatide (CT-388), Placebo
Primary Endpoints
Change in HbA1c from baseline; Percent change in bodyweight from baseline
Study Period
2024
Research Compliance Notice

All data presented on this page is for laboratory research purposes only. Enicepatide is referenced here as a research reagent. This page does not constitute medical advice, clinical guidance, or endorsement of any compound for human or animal use. All referenced studies are available via PubMed (PMID: 41319798) and the DOI-linked journal publication. Researchers must consult applicable institutional and regulatory frameworks before conducting any protocols.

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