EnicepatideResearch, Evidence & Safety Profile

Enicepatide, known during early development as CT-388, is an investigational once-weekly subcutaneous dual GLP-1/GIP receptor agonist being developed by F. Hoffmann-La Roche AG (and its U.S. member Genentech) for chronic weight management. The molecule originated at Carmot Therapeutics, which Roche acquired in 2024, and sits in the same mechanistic class as the approved dual agonist tirzepatide while being a distinct molecular entity with a different signalling profile.

At the American Diabetes Association (ADA) 2026 Scientific Sessions in June 2026, Roche presented late-breaking Phase 2 data from the CT388-103 trial reporting approximately 22.5% placebo-adjusted mean body weight reduction at 48 weeks in people living with overweight or obesity. A separate Phase 2 study, CT388-104, is evaluating enicepatide in participants who have obesity or overweight together with type 2 diabetes. Roche has stated that the program is advancing into Phase 3 and that a multi-arm combination trial — including a combination with the amylin analog petrelintide — is planned to launch in 2026.

Enicepatide is one of several next-generation incretin therapies that read out at ADA 2026, alongside full Phase 3 data for the triple agonist retatrutide and the dual GLP-1/glucagon agonist survodutide. The crowded pipeline reflects a field testing whether different receptor combinations and signalling designs can improve on the efficacy and tolerability of first-generation incretin drugs.

As of June 2026, enicepatide is not approved by the U.S. Food and Drug Administration or any other regulatory agency for any indication. It is in Phase 2 clinical development with Phase 3 planned.

Regulatory caution: Enicepatide is an investigational compound. It has not been reviewed for safety and efficacy at any dose for any indication outside of clinical trial protocols. Any source claiming to supply enicepatide outside of an approved clinical trial should be regarded with serious skepticism — identity, purity, and safety of such products cannot be verified.

Enicepatide is engineered to activate two incretin receptors — the glucagon-like peptide-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor — through a single molecule. This is the same dual-receptor strategy used by tirzepatide, but enicepatide is designed with a distinct pharmacology intended to sustain receptor activity over time.

• GLP-1 receptor activation: Slows gastric emptying, enhances glucose-dependent insulin secretion, suppresses post-meal glucagon, and signals through appetite-regulating centers to reduce caloric intake.
• GIP receptor activation: The role of GIP agonism in weight regulation is an area of active research. Co-agonism with GLP-1 is thought to improve metabolic effects and may contribute to better gastrointestinal tolerability relative to GLP-1 alone, though the mechanism is not fully resolved.
• Biased signalling design: Enicepatide is reported to be engineered for minimal-to-no beta-arrestin recruitment at both receptors. Beta-arrestin recruitment normally drives receptor internalization and desensitization — the gradual loss of cellular responsiveness with sustained stimulation. By limiting that pathway, the molecule is designed to maintain prolonged pharmacological activity, the working rationale for once-weekly dosing and potentially durable efficacy.

The net intended effect is sustained GLP-1/GIP co-agonism that reduces appetite and caloric intake while supporting glycemic control. Whether the biased-signalling design translates into clinically meaningful advantages over existing dual agonists is a question that Phase 3 trials and head-to-head data — which do not yet exist — would need to answer.

The following potential benefits are based on Phase 2 human clinical trial data presented at ADA 2026 (CT388-103) and earlier-phase dose-finding work. All findings are from controlled clinical trials and may not be representative of uncontrolled use. Phase 3 data does not yet exist.

• Body weight reduction: The Phase 2 CT388-103 trial reported approximately 22.5% placebo-adjusted mean body weight reduction at 48 weeks. This magnitude is in the range of the published results for tirzepatide (≈20% at 72 weeks in Phase 3 SURMOUNT-1) and below the Phase 2 figure for retatrutide (24.2% at 48 weeks), though cross-trial comparisons are imperfect because designs, populations, doses, and durations differ.
• Glycemic effects: As a GLP-1/GIP co-agonist, enicepatide is expected to improve glucose control through glucose-dependent insulin secretion and glucagon suppression. The CT388-104 study is specifically evaluating efficacy and safety in people who have overweight or obesity with type 2 diabetes.
• Durability rationale (mechanistic): The biased-signalling design is intended to limit receptor desensitization and sustain activity. This is a mechanistic hypothesis; its clinical relevance for long-term weight maintenance has not been established in published outcome data.
• Combination potential: Roche has disclosed plans to study enicepatide in combination with petrelintide, an amylin analog. The strategy reflects a broader hypothesis that amylin agonism and incretin agonism act through complementary satiety pathways and may produce additive weight loss.

Phase 2 figures should be interpreted with appropriate caution. Weight-loss magnitude in incretin trials commonly shifts between Phase 2 and Phase 3 — sometimes upward as trial duration lengthens, sometimes downward as broader populations dilute the strongest responders. Phase 3 readouts are the next meaningful data point.

Enicepatide's safety profile is characterized only through Phase 2 as of June 2026. Phase 3 data does not yet exist, and the long-term safety picture is not established.

• Gastrointestinal effects: As with the GLP-1 and GLP-1/GIP class, nausea, vomiting, diarrhea, and constipation are the most commonly anticipated adverse events, typically most pronounced during dose escalation. Full tolerability and discontinuation data from the Phase 2 program will be detailed in peer-reviewed publication.
• Injection site reactions: As a once-weekly subcutaneous peptide, mild, transient injection site reactions (redness, irritation) are possible, consistent with the broader class.
• Hypoglycemia: Incretin-receptor agonism is largely glucose-dependent, so the risk of hypoglycemia from enicepatide alone is low. Risk increases substantially when combined with insulin or sulfonylureas.
• Class-level considerations: GLP-1-based therapies carry class labeling considerations including a boxed warning for thyroid C-cell tumors based on rodent data (clinical relevance in humans remains uncertain), gallbladder-related events, and pancreatitis signals. Whether and how these class-level items apply to enicepatide will be characterized as Phase 3 data and regulatory review proceed.
• Long-term safety: As an investigational compound in Phase 2, enicepatide's long-term safety profile is not characterized. Phase 3 trials and, if approved, post-market surveillance would establish the long-term risk picture.

Because the published safety data set is limited to early- and mid-stage trials, any characterization here is provisional and may change as larger and longer studies report.

Disclaimer: Enicepatide is investigational and not approved for any indication. The following information reflects publicly disclosed clinical trial design for educational purposes only. These are not recommendations for self-administration.

Enicepatide is being developed for once-weekly subcutaneous administration. Like other incretin therapies, its Phase 2 trials used a stepwise dose-escalation approach designed to improve gastrointestinal tolerability before reaching maintenance dosing. Specific dose magnitudes and the full dose-response relationship are expected in peer-reviewed publication following the ADA 2026 presentation.

Phase 3 dose selection will follow standard regulatory practice — anchored on the Phase 2 dose-response data and intended to characterize efficacy and safety across a clinically relevant range.

As of June 2026, enicepatide has a mid-stage clinical data set, with the most recent results disclosed as a late-breaking presentation at the ADA 2026 Scientific Sessions. Peer-reviewed publication of the full Phase 2 data is anticipated.

• Phase 2 CT388-103 (ADA 2026): Phase 2 trial in adults with overweight or obesity. Reported approximately 22.5% placebo-adjusted mean body weight reduction at 48 weeks. Full secondary endpoints, body-composition data, and tolerability details are expected in publication.
• Phase 2 CT388-104 (ongoing): Evaluating efficacy, safety, and tolerability of enicepatide in participants who have overweight or obesity together with type 2 diabetes.
• Phase 3 program (planned 2026): Roche has stated that enicepatide is advancing into Phase 3 development. Endpoint design and trial sizes will be disclosed at trial registration.
• Combination program (planned 2026): A multi-arm combination trial is planned, including a combination of enicepatide with the amylin analog petrelintide. The hypothesis is that incretin plus amylin agonism may produce greater weight loss than either component alone.
• Origin: Enicepatide (CT-388) was developed at Carmot Therapeutics and entered Roche's pipeline through Roche's 2024 acquisition of Carmot. The acquisition gave Roche a portfolio of incretin-based candidates and signaled the company's entry into the obesity-therapeutics field.

Enicepatide sits within a rapidly expanding incretin landscape. The approved dual GLP-1/GIP agonist tirzepatide established the class commercially; investigational entrants now include the triple agonist retatrutide, the GLP-1/glucagon agonist survodutide, and oral candidates. Comparative effectiveness across these mechanisms will require head-to-head trials, which do not yet exist for enicepatide.

As of June 2026, enicepatide is an investigational new drug in active clinical development. It has not received FDA approval, EMA approval, or approval from any other regulatory agency for any indication.

• United States: Investigational. Available only within approved clinical trial protocols. Not compoundable — enicepatide is a proprietary peptide produced through company-controlled manufacturing, not a generic peptide that compounding pharmacies can legally replicate.
• European Union: No regulatory status established. The program is being designed for global development.
• Off-label or grey market access: As a proprietary investigational drug, enicepatide's authorized availability is limited to clinical trials. Any source claiming to supply enicepatide outside of a trial should be regarded with serious skepticism — identity, purity, and safety of such products cannot be verified, and the legal exposure to suppliers and purchasers is significant.
• Expected timeline: Phase 3 trials are planned to begin in 2026. Because Phase 3 obesity trials commonly run 68–80 weeks for primary efficacy endpoints, a regulatory submission and any potential approval would not be expected for several years. This is speculative and depends on Phase 3 outcomes and regulatory review.