Enicepatide (CT-388 / RO7795068)

Overview

Enicepatide (development codes CT-388 and RO7795068) is an investigational once-weekly subcutaneous peptide-based dual GLP-1/GIP receptor agonist developed by Roche/Genentech for obesity and type 2 diabetes. The molecule is unusual among incretin therapies in being a 'biased' agonist: it activates GLP-1R and GIPR with cAMP signaling but with minimal beta-arrestin recruitment, a design intended to maximize metabolic signaling while reducing receptor desensitization. The International Nonproprietary Name 'enicepatide' was assigned in 2026 (RG6640). Roche acquired the asset through the 2024 Carmot Therapeutics acquisition. In the 48-week Phase 2 CT388-103 trial (NCT06525935) in 469 adults with obesity or overweight plus a comorbidity, the 24 mg once-weekly dose produced placebo-adjusted weight loss of 22.5% (efficacy estimand; 18.3% treatment-regimen estimand). At week 48, 95.7% of treated participants achieved at least 5% weight loss, 87% at least 10%, 47.8% at least 20%, and 26.1% at least 30%. 54% achieved BMI <30 (resolution of obesity) versus 13% in the placebo arm. No weight-loss plateau was observed at week 48 — the curve was still descending at study end. 73% of participants with baseline prediabetes returned to normoglycemia. Treatment discontinuation due to adverse events was 5.9% in CT-388 arms versus 1.3% in placebo. Two global Phase 3 trials are recruiting as of June 2026: NCT07351045 (obesity without T2D, week-72 primary endpoint) and NCT07351058 (T2D). A Phase 2 combination study with the amylin analog petrelintide is also planned for mid-2026.

Mechanism of Action

Enicepatide is a unimolecular peptide-based agonist of both the GLP-1 receptor and the GIP receptor. Unlike tirzepatide, which has a relatively balanced GIP/GLP-1 profile, enicepatide is engineered as a cAMP-signal-biased agonist at both receptors with minimal beta-arrestin recruitment, which in preclinical models corresponds to less receptor internalization and sustained signaling. In humans, this is hypothesized to support both the magnitude of weight loss observed (22.5% placebo-adjusted at week 48) and the absence of a plateau at end-of-study. The molecule is delivered as a once-weekly subcutaneous injection via an integrated drug-device combination product.

Potential Benefits

• Best-in-class Phase 2 weight loss (22.5% placebo-adjusted at 48 weeks, 24 mg)
• 54% of treated participants resolved obesity (BMI <30) vs 13% placebo
• No weight-loss plateau observed at week 48
• 73% of baseline-prediabetic patients returned to normoglycemia
• Low treatment discontinuation (5.9%) compared with class norms

Research Dosage Notes

The following reflects doses used in published research studies. This is not medical advice.

Phase 2 escalation up to 24 mg once weekly subcutaneous. Phase 3 dosing regimens being evaluated via integrated drug-device combination product.

Amino Acid Sequence

Side Effects & Safety

• Mostly mild-to-moderate gastrointestinal: nausea, diarrhea, vomiting
• 5.9% discontinuation due to adverse events at 24 mg
• Class-typical signal; no new or unexpected safety signals reported

Synergistic Compounds

The following compounds have been studied alongside Enicepatide (CT-388 / RO7795068) for potential complementary or synergistic effects:

Related Peptides

Learn More

References & Further Reading

• Roche June 1, 2026 ADA 2026 portfolio announcement
• Roche January 27, 2026 Phase II topline results
• CT-388 Phase 1 pharmacology (Mol Metab 2026)
• Phase 3 obesity trial NCT07351045
• Phase 2 CT388-103 NCT06525935