How does CT-388 compare to tirzepatide?

Both are dual GLP-1/GIP agonists, but CT-388 differs in two key ways: balanced receptor engagement (equimolar GLP-1/GIP vs tirzepatide's 9:1 GIP-bias) and cAMP-biased signaling (minimizing β-arrestin-mediated receptor desensitization). Phase 2 CT-388 hit 22.5% placebo-adjusted weight loss at 48 weeks; SURMOUNT-1 tirzepatide hit 17.8% at 72 weeks. Direct comparison is limited (cross-trial, different estimands), but CT-388's trajectory was still descending at 48 weeks, suggesting greater potential with longer exposure.

What does 'signaling-biased' mean for CT-388?

GLP-1 and GIP receptors can activate two pathways: the canonical Gαs-cAMP pathway (drives insulin secretion, satiety, slowed gastric emptying) and β-arrestin recruitment (causes receptor internalization and desensitization). CT-388 preferentially activates cAMP with minimal β-arrestin recruitment at both receptors. Result: more durable pharmacologic activity and potentially better efficacy over time.

When will CT-388 be available?

Phase 3 ENITH1 and ENITH2 trials start Q1 2026. Roche's guidance points to approximately 2030 launch. It is not currently available outside clinical trials.

CT-388

Roche/Genentech's next-generation dual GLP-1/GIP receptor agonist. Phase 2 showed 22.5% placebo-adjusted weight loss at 48 weeks — competitive with retatrutide. Phase 3 ENITH program starts Q1 2026.

ModerateLimited Data

What is CT-388?

CT-388 (RO7795068) is a once-weekly subcutaneous signaling-biased dual GLP-1/GIP receptor agonist developed by Roche/Genentech after their $2.7 billion acquisition of Carmot Therapeutics in December 2023. Unlike tirzepatide's ~9:1 GIP-biased receptor engagement, CT-388 is engineered for balanced equimolar activation of both GLP-1R and GIPR — and it achieves this through cAMP-biased signaling with minimal β-arrestin recruitment at either receptor (reducing receptor desensitization and extending pharmacologic action). Phase 2 results (469 patients, 48 weeks, Jan 2026): 22.5% placebo-adjusted weight loss at the 24 mg dose, with 87% of patients achieving ≥10% weight loss and 47.8% achieving ≥20%. Critically, no weight-loss plateau was observed at 48 weeks — the curve was still descending. Phase 3 (ENITH1, ENITH2) starts Q1 2026 with potential launch around 2030.

Why People Talk About It

Best-in-class Phase 2 weight loss (22.5% placebo-adjusted at 48 weeks)

Moderate

Balanced GLP-1/GIP engagement vs tirzepatide's GIP-bias

Moderate

Type 2 diabetes glycemic control

Moderate

Combination with petrelintide for enhanced effect

Limited

Low treatment-related discontinuation (5.9% vs tirzepatide class norm ~10-15%)

Moderate

How It Works

CT-388 activates two receptors at once: GLP-1 (which reduces appetite and improves blood sugar) and GIP (which enhances insulin response to meals). This is the same combination tirzepatide uses, but CT-388 activates them in a more balanced way and uses 'biased signaling' to prevent the receptors from desensitizing over time — which may mean better long-term efficacy.

Common Questions

Safety Information

Important Safety Notes

Common Side Effects

Nausea, vomiting, diarrhea (typical GLP-1 class, mostly mild-to-moderate)Decreased appetiteMost GI AEs occurred during dose escalation

Cautions

• Not FDA-approved — investigational drug in Phase 2/3
• Long-term safety beyond 48 weeks not yet established
• Cardiovascular outcomes data not yet available

What We Don't Know

No CVOT (cardiovascular outcomes trial) data yet — CV benefit claimed by GLP-1 class may not automatically transfer. Long-term durability and safety beyond 48 weeks are not established. Real-world adherence and performance outside controlled trials are unknown. Whether biased signaling provides clinically meaningful durability advantage vs tirzepatide will be tested in Phase 3.

Published Research

8 studies

Effects of CT-388, a once-weekly signaling-biased dual GLP-1/GIP receptor agonist, on weight loss and glycemic control in preclinical models and participants with obesity.

Clinical TrialPMID: 41319798

Incretin signaling at the crossroads of metabolism, inflammation, and tumorigenesis.

ReviewPMID: 41138841

Strategic Design of Triple GLP-1R/GCGR/GIPR Agonists with Varied Receptor Potency.

PreclinicalPMID: 40958513

Biased agonism of GLP-1R and GIPR enhances glucose lowering and weight loss, with dual GLP-1R/GIPR biased agonism yielding greater efficacy.

PreclinicalPMID: 40460831

Investigational and emerging GIP receptor-based therapies for the treatment of obesity.

ReviewPMID: 38984950

Duodenal enteroendocrine cells and GIP as treatment targets for obesity and type 2 diabetes.

ReviewPMID: 38320643

Spatiotemporal GLP-1 and GIP receptor signaling and trafficking/recycling dynamics induced by selected receptor mono- and dual-agonists.

PreclinicalPMID: 33556643

Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist.

PreclinicalPMID: 32730231

Mechanism of Action

CT-388 is a unimolecular peptide-based dual GLP-1R/GIPR agonist with two distinguishing pharmacologic features: (1) balanced equimolar receptor engagement — unlike tirzepatide which is ~9:1 GIP-biased; and (2) cAMP signal-biased activation at both receptors with minimal β-arrestin recruitment. The biased signaling reduces receptor internalization and desensitization, producing more prolonged pharmacologic activity. GLP-1R agonism drives glucose-dependent insulin secretion, satiety via hypothalamic appetite centers, and slowed gastric emptying. GIPR agonism enhances insulin response during meals and may improve lipid metabolism. Phase 2 (NCT06525935, 469 patients, 48 weeks): 24 mg weekly produced 22.5% placebo-adjusted weight loss (efficacy estimand), 18.3% (treatment-regimen estimand), with 95.7% achieving ≥5%, 87% ≥10%, 47.8% ≥20%, and 26.1% ≥30% weight loss. No plateau observed at 48 weeks. 73% of prediabetic CT-388 participants achieved normal blood glucose vs 7.5% placebo. Phase 1b T2D cohort: 50% of 22 mg patients achieved HbA1c <5.7% (diabetes remission threshold) at 12 weeks.

Evidence Snapshot

Overall Confidence60%

Human Clinical Evidence

Moderate and rapidly expanding. Phase 1 (NCT04838405): dose-dependent weight loss and glycemic improvement, published in Molecular Metabolism (PMID: 41319798). Phase 2 CT-388-103 (469 patients, 48 weeks): 22.5% placebo-adjusted weight loss, no plateau, 5.9% discontinuation. Phase 2 CT-388-104 (~360 T2D patients) ongoing. Phase 3 ENITH1 and ENITH2 start Q1 2026.

Animal / Preclinical

Strong. Preclinical data in rodents and non-human primates showed dose-dependent weight reduction, improved glycemic control, and improved MASH pathology. The biased-agonism design rationale (Rodriguez et al., Cell Rep Med 2025, PMID: 40460831) is independently validated.

Mechanistic Rationale

Strong. Dual GLP-1/GIP agonism is clinically validated by tirzepatide. The CT-388 design refinements (balanced receptor engagement + cAMP-biased signaling) are mechanistically sound responses to characterized limitations of first-generation dual agonists. Tirzepatide's 9:1 GIP-bias is well-documented (Willard et al., JCI Insight 2020, PMID: 32730231).

Forms & Administration

CT-388 is administered as a once-weekly subcutaneous injection. Phase 2 tested doses up to 24 mg weekly with multiple up-titration schemes. Currently only available through clinical trials.

Use Cases & Evidence Levels

Best-in-class Phase 2 weight loss (22.5% placebo-adjusted at 48 weeks)

Moderate70%

Balanced GLP-1/GIP engagement vs tirzepatide's GIP-bias

Moderate70%

Type 2 diabetes glycemic control

Moderate70%

Combination with petrelintide for enhanced effect

Limited15%

Low treatment-related discontinuation (5.9% vs tirzepatide class norm ~10-15%)

Moderate70%

Safety Profile

Safety Information

Common Side Effects

Nausea, vomiting, diarrhea (typical GLP-1 class, mostly mild-to-moderate)Decreased appetiteMost GI AEs occurred during dose escalation

Cautions

• Not FDA-approved — investigational drug in Phase 2/3
• Long-term safety beyond 48 weeks not yet established
• Cardiovascular outcomes data not yet available

What We Don't Know

Published Research

8 studies

Effects of CT-388, a once-weekly signaling-biased dual GLP-1/GIP receptor agonist, on weight loss and glycemic control in preclinical models and participants with obesity.

Clinical TrialPMID: 41319798

Incretin signaling at the crossroads of metabolism, inflammation, and tumorigenesis.

ReviewPMID: 41138841

Strategic Design of Triple GLP-1R/GCGR/GIPR Agonists with Varied Receptor Potency.

PreclinicalPMID: 40958513

Biased agonism of GLP-1R and GIPR enhances glucose lowering and weight loss, with dual GLP-1R/GIPR biased agonism yielding greater efficacy.

PreclinicalPMID: 40460831

Investigational and emerging GIP receptor-based therapies for the treatment of obesity.

ReviewPMID: 38984950

Duodenal enteroendocrine cells and GIP as treatment targets for obesity and type 2 diabetes.

ReviewPMID: 38320643

Spatiotemporal GLP-1 and GIP receptor signaling and trafficking/recycling dynamics induced by selected receptor mono- and dual-agonists.

PreclinicalPMID: 33556643

Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist.

PreclinicalPMID: 32730231

Related Peptides

Tirzepatide

StrongBeginner

A dual GIP/GLP-1 receptor agonist FDA-approved for diabetes and weight management, producing the largest weight loss seen in clinical trials.

Semaglutide

StrongBeginner

A GLP-1 receptor agonist FDA-approved for type 2 diabetes and chronic weight management, one of the most widely prescribed peptide drugs.

Retatrutide

Emerging

An investigational triple agonist (GIP/GLP-1/glucagon) from Eli Lilly. Not FDA-approved. Phase III TRIUMPH-4 results showed 23.7% weight loss — the most of any obesity drug in development.

Mazdutide

Moderate

The world's first approved dual GLP-1/glucagon receptor agonist, developed by Innovent Biologics (China). Approved in China for obesity and type 2 diabetes. Phase 3 trials showed up to 20.1% weight loss.

Survodutide

Emerging

An investigational dual glucagon/GLP-1 receptor agonist developed by Boehringer Ingelheim and Zealand Pharma. Not FDA-approved. Phase 2 trials showed up to 14.9% weight loss at 46 weeks and significant MASH resolution — Phase 3 SYNCHRONIZE program is underway.

Petrelintide

Moderate

Zealand Pharma's long-acting amylin analog, partnered with Roche in a $5.3B deal. Phase 2b ZUPREME-1 showed 10.7% weight loss at 42 weeks with placebo-like tolerability — the 'tolerability play' in the amylin class.

Quick Facts

Class: Incretin Mimetic
Evidence: Moderate
Safety: Limited Data
Updated: Apr 2026
Citations: 8PubMed

Also known as

RO7795068

Evidence Score

Overall Confidence60%

Clinical Trials

View Clinical Trials

Links to ClinicalTrials.gov for reference. Listing does not imply endorsement.