CT-388
Medium EvidenceAn investigational once-weekly subcutaneous dual GLP-1 and GIP receptor agonist from Roche/Genentech (acquired with Carmot Therapeutics for ~$2.7 billion; Roche code RO7795068). CT-388 is engineered as a 'signal-biased' agonist: it potently activates both incretin receptors but recruits little or no beta-arrestin, which is expected to reduce receptor internalization and desensitization and thereby prolong pharmacological activity. In a Phase 1b study it produced ~18.8% placebo-adjusted weight loss at 24 weeks, and in the Phase 2 CT388-103 dose-finding trial (469 adults with obesity/overweight) it delivered a placebo-adjusted mean weight loss of 22.5% at 48 weeks (efficacy estimand; 18.3% treatment-regimen estimand) at the top 24 mg dose, without reaching a plateau. Roche advanced CT-388 into Phase 3 in the first half of 2026, positioning it as a late-entrant competitor to tirzepatide (Zepbound) with a potentially differentiated biased-signaling mechanism.
What It Is
CT-388 (Roche development code RO7795068; originally from Carmot Therapeutics) is an investigational once-weekly, subcutaneously injected dual agonist of the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, being developed for obesity, type 2 diabetes, and obesity-related comorbidities. Roche acquired the asset through its ~$2.7 billion purchase of California-based Carmot Therapeutics, announced in December 2023 and closed in January 2024, which gave Roche a portfolio of incretin candidates (including the injectable CT-388 and an oral small-molecule GLP-1, CT-996). Like tirzepatide, CT-388 co-activates GLP-1 and GIP receptors - the two gut hormones that integrate nutrient signals to control appetite, insulin secretion, and energy homeostasis - so it suppresses appetite, slows gastric emptying, and improves glycemic control. What Roche/Carmot describe as distinctive is the pharmacology of that activation: CT-388 was designed as a 'signal-biased' (G-protein-biased) agonist that potently stimulates both receptors while recruiting minimal to no beta-arrestin. Because beta-arrestin recruitment drives receptor internalization and downstream desensitization (tachyphylaxis), minimizing it is hypothesized to preserve receptor sensitivity and produce more sustained, durable pharmacological activity across the weekly dosing interval. In the Phase 1b study reported in May 2024, once-weekly CT-388 titrated over 24 weeks produced ~18.8% placebo-adjusted weight loss; 100% of treated participants lost >5% of body weight, 85% lost >10%, 70% lost >15%, and 45% lost >20%, and all participants who had prediabetes at baseline became normoglycemic by week 24. In January 2026 Roche reported positive topline Phase 2 results from CT388-103, a 48-week, randomized, double-blind, placebo-controlled dose-finding study in 469 adults with obesity or overweight plus at least one weight-related comorbidity. The trial met its primary endpoint with a placebo-adjusted mean weight loss of 22.5% (efficacy estimand) / 18.3% (treatment-regimen estimand) at the 24 mg dose at week 48, with a clear dose-response and no plateau by week 48; 95.7% of participants on 24 mg achieved >=5% weight loss, 87% >=10%, 47.8% >=20%, and 26.1% >=30%, and 54% reached 'resolution of obesity' (BMI <30) versus 13% on placebo. Tolerability was consistent with the incretin class, with mostly mild-to-moderate gastrointestinal adverse events and no new or unexpected safety signals. On the strength of these data Roche moved CT-388 into Phase 3 in the first half of 2026 and has signaled interest in combination studies (for example pairing CT-388 with an amylin analog such as petrelintide, also from the Carmot/Roche pipeline). CT-388 is an investigational, manufacturer-developed biologic being studied in regulated clinical trials - not an approved medicine and not a self-sourced 'research peptide.'
Regulatory Status
Investigational (not approved by any regulator). In Phase 3 clinical development for obesity as of mid-2026; no marketing application yet.
Why Researchers Study It
CT-388 is a test of whether a 'signal-biased' incretin agonist - one that fully activates GLP-1 and GIP receptors but avoids the beta-arrestin recruitment that drives receptor desensitization - can translate into deeper or more durable weight loss than the current dual agonist standard, tirzepatide. It is also Roche's flagship attempt to enter the obesity market it entered late, and a platform for combination regimens (e.g., with an amylin analog) that could push efficacy toward bariatric-surgery-like ranges.
Proposed Mechanisms
- GLP-1 receptor agonism: activates the GLP-1 receptor to enhance glucose-dependent insulin secretion, suppress glucagon, slow gastric emptying, and reduce appetite and food intake via central and peripheral pathways.
- GIP receptor agonism: co-activates the GIP receptor, which contributes additional insulinotropic effect and is thought to improve the tolerability and metabolic profile of combined incretin agonism.
- Biased (G-protein-selective) signaling: potent receptor activation with minimal to no beta-arrestin recruitment, reducing receptor internalization and desensitization (tachyphylaxis) and hypothesized to sustain pharmacological activity across the weekly dosing interval.
- Energy homeostasis integration: by engaging the two principal incretin pathways that read out nutrient status, CT-388 lowers energy intake and improves insulin sensitivity, driving fat-mass loss and glycemic improvement.
- Molecular engineering for weekly dosing: a peptide agonist optimized for a pharmacokinetic profile that supports once-weekly subcutaneous administration.
Evidence Snapshot
| Study Type | Model | Outcome | Link |
|---|---|---|---|
| RCT (human, Phase 2 - CT388-103) | 469 adults with obesity or overweight plus >=1 weight-related comorbidity; once-weekly subcutaneous CT-388 (multiple dose-escalation arms up to 24 mg) vs placebo over 48 weeks | Met primary endpoint: placebo-adjusted mean weight loss 22.5% (efficacy estimand) / 18.3% (treatment-regimen estimand) at 24 mg at week 48; clear dose-response, no plateau; 95.7% achieved >=5%, 87% >=10%, 47.8% >=20%, 26.1% >=30%; 54% reached BMI <30 vs 13% placebo | Source |
| RCT (human, Phase 1b) | Adults with obesity; once-weekly subcutaneous CT-388 titrated over 24 weeks vs placebo | ~18.8% placebo-adjusted weight loss at 24 weeks; 100% of treated participants lost >5%, 85% >10%, 70% >15%, 45% >20%; all baseline-prediabetes participants became normoglycemic; well tolerated (mostly mild-moderate GI events) | Source |
| Mechanistic / pharmacology | In vitro receptor signaling characterization of CT-388 at GLP-1 and GIP receptors | Potent dual receptor activation with minimal/no beta-arrestin recruitment ('signal-biased' agonism), predicted to minimize receptor internalization and desensitization and prolong activity | Source |
| Development / regulatory milestone | Roche obesity program decision following Phase 2 topline | CT-388 advanced into Phase 3 clinical development for obesity in the first half of 2026; combination studies (e.g., with amylin analog petrelintide) signaled | Source |
| Corporate / acquisition context | Roche acquisition of Carmot Therapeutics | Roche acquired CT-388 (and the broader incretin portfolio) via ~$2.7B purchase of Carmot Therapeutics (announced Dec 2023, closed Jan 2024); Roche code RO7795068 | Source |
| Independent clinical summary | Phase 2 topline coverage and comparison to approved incretins | 22.5% placebo-adjusted weight loss reported as competitive with tirzepatide-class efficacy; true differentiation may depend on head-to-head and combination data | Source |
Commonly Discussed Benefits
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Safety & Cautions
- Investigational and not approved: CT-388 is in Phase 3 development and is not available by prescription; efficacy and safety claims rest on Phase 1b/Phase 2 data and remain to be confirmed in Phase 3.
- No self-sourcing: CT-388 is a proprietary Roche/Genentech biologic studied only in controlled trials. Material sold online as 'CT-388' is not the clinical drug and cannot be assumed to be authentic, pure, or safe.
- Gastrointestinal effects: like all GLP-1/GIP incretin agonists, CT-388 commonly causes nausea, vomiting, diarrhea, and constipation, usually mild-to-moderate and dose-dependent during titration.
- Class-level considerations: incretin agonists carry class labeling considerations (e.g., gallbladder events, pancreatitis risk signals, and a boxed warning for thyroid C-cell tumors in rodents for some agents); CT-388's long-term and class-specific risk profile is not yet established.
- Efficacy estimand vs real-world: the headline 22.5% figure is the efficacy (on-treatment) estimand; the treatment-regimen estimand (18.3%) better reflects real-world adherence, and durability beyond 48 weeks and after discontinuation is unknown.
- Not a first-line or verified therapy: results are topline/press-release stage for Phase 2; full peer-reviewed publication and Phase 3 outcomes are needed before clinical conclusions.
Comparisons
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Citations
- [1] Roche announces positive Phase II results for its dual GLP-1/GIP receptor agonist CT-388 in people living with obesity (Jan 2026) PubMed
- [2] Roche reports positive Phase Ib results for its dual GLP-1/GIP receptor agonist CT-388 in people with obesity (May 2024) PubMed
- [3] Genentech Announces Positive Phase II Results for Its Dual GLP-1/GIP Receptor Agonist CT-388 in People Living With Obesity PubMed
- [4] Investigational Dual GLP-1/GIP Agonist CT-388 Demonstrates 22.5% Placebo-Adjusted Weight Loss in Phase 2 Obesity Trial (Patient Care Online) PubMed
- [5] Roche moves obesity asset CT-388 into Phase III (European Biotechnology) PubMed
- [6] Roche, trailing in obesity, showcases new data for GLP-1 shot (BioPharma Dive) PubMed
- [7] Roche Obesity Drug's Phase 2 Results Are Competitive, But True Test May Come From Combo Studies (MedCity News) PubMed
- [8] A Study of CT-388 (RO7795068) in Participants with Obesity or Overweight (Roche ForPatients trial listing) PubMed
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