CT-388

What is CT-388?

CT-388 (RO7795068; INN enicepatide, assigned 2026) 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. Roche initiated two Phase 3 obesity trials (ENITH1 and ENITH2) in Q1 2026, and the program now operates under the INN enicepatide. A type-2-diabetes obesity Phase 2 readout is guided for late 2026, and a Phase 2 combination study with petrelintide (Zealand-partnered amylin analog) is targeted to enroll its first patient around mid-2026 — pairing what Roche has framed as 'a highly tolerable amylin with a strong GLP-1/GIP.' A subsequent combination with the oral GLP-1 agonist CT-996 is also planned. Potential launch is around 2030.

What CT-388 Is Investigated For

CT-388 — now also known by the INN enicepatide, assigned in 2026 — is Roche/Genentech's next-generation dual GLP-1/GIP receptor agonist investigated for weight loss, type 2 diabetes glycemic control, and combinations with complementary agents like petrelintide and the oral GLP-1 CT-996. It was engineered specifically to address the characterized limitations of tirzepatide through balanced equimolar receptor engagement (rather than tirzepatide's 9:1 GIP-bias) and cAMP-biased signaling that minimizes β-arrestin-mediated receptor desensitization. The strongest evidence as of mid-2026 is the 48-week Phase 2 CT-388-103 trial (469 patients), which produced 22.5% placebo-adjusted weight loss at the 24 mg dose with 87% of patients achieving ≥10% weight loss, 47.8% achieving ≥20%, a crisp 5.9% treatment-related discontinuation rate, and — notably — no weight-loss plateau at study end. These numbers are competitive with retatrutide and cross-trial exceed tirzepatide's SURMOUNT-1 results, though the comparison is methodologically constrained. Roche initiated the Phase 3 ENITH1 and ENITH2 obesity trials in Q1 2026 and is guiding a Phase 2 type-2-diabetes obesity readout for late 2026; a Phase 2 enicepatide-plus-petrelintide combination study is targeted to enroll its first patient around mid-2026 (Roche/Zealand framing: 'pairing a highly tolerable amylin with a strong GLP-1/GIP'), with a CT-996 oral combination also in planning. The honest caveats are that potential launch is around 2030, no cardiovascular outcomes data yet exists, long-term durability beyond 48 weeks is unproven, and whether the biased-agonism design translates into clinically meaningful durability gains is exactly what Phase 3 will test. The drug is investigational and not available outside Roche-sponsored trials.

History & Discovery

CT-388 originated at Carmot Therapeutics, a small California biotech founded around a chemistry platform for engineering peptide multi-receptor agonists with biased signaling profiles. The molecule was conceived as a deliberate response to the characterized pharmacology of tirzepatide — specifically, its imbalanced ~9:1 GIP-over-GLP-1 receptor engagement and its β-arrestin-driven receptor desensitization — by designing a unimolecular dual agonist with balanced potency at both receptors and cAMP-biased activation that minimizes arrestin recruitment. Carmot brought the program through Phase 1 and into Phase 2 before Roche acquired the company in December 2023 for $2.7 billion upfront, with CT-388 (renamed RO7795068) as the central asset. Roche reported the 48-week Phase 2 data in early 2026, initiated the Phase 3 ENITH1 and ENITH2 obesity trials in Q1 2026, and the molecule was assigned the International Nonproprietary Name 'enicepatide' the same year — following the same developer-code-to-INN convention by which tirzepatide (LY3298176) and retatrutide (LY3437943) were renamed ahead of approval. On the company's Q1 2026 earnings call, Roche disclosed plans for a Phase 2 enicepatide-plus-petrelintide combination study with first patient enrollment around mid-2026 and a subsequent combination with the oral GLP-1 CT-996, positioning the molecule as the cornerstone of Roche's obesity pipeline. The compound has not been approved by any regulatory body.

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.

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

Research Gaps & Open Questions

What the current literature has not yet settled about CT-388:

• 01Cardiovascular outcomes — no CVOT has been conducted; whether CT-388 will replicate the MACE-reduction signals seen with semaglutide and tirzepatide is not established.
• 02Long-term safety beyond 48 weeks — pancreatitis, gallbladder disease, retinopathy progression, and rare oncologic signals require multi-year exposure data the program has not yet generated.
• 03Whether biased agonism delivers a clinically meaningful durability advantage — the in vitro and preclinical case for cAMP-biased, β-arrestin-sparing signaling is strong, but Phase 3 data are needed to show that this translates into greater long-term weight loss or reduced tachyphylaxis vs. tirzepatide.
• 04Body-composition impact — sub-studies on lean mass, bone density, and resistance-training mitigation strategies during rapid CT-388-induced weight loss are not yet published.
• 05Performance in real-world adherence conditions outside controlled trials, where titration deviations and concurrent medications are far more common.
• 06Direct head-to-head comparisons with tirzepatide and retatrutide — current efficacy comparisons are cross-trial, with all the methodological caveats that implies.

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.

Dosing & Protocols

The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.

CT-388 is not approved by the FDA or any other regulatory authority. The doses cited above reflect investigational protocols, not prescribing guidance. Any use outside an authorized clinical trial carries unquantified risk.

Timeline of Effects

Common Questions

Who CT-388 Is NOT For

Drug & Supplement Interactions

Documented drug-interaction data for CT-388 in humans are essentially absent because the product is investigational. The class-level interactions known from semaglutide and tirzepatide are the best available proxies. Concurrent use with insulin or insulin secretagogues (sulfonylureas, meglitinides) materially raises hypoglycemia risk in patients with diabetes, and downward titration of those agents at CT-388 initiation and dose escalation is the established mitigation. The slowed gastric emptying induced by dual GLP-1/GIP agonism alters absorption rate and peak concentrations of orally administered medications, a particular concern for narrow-therapeutic-index agents (warfarin, levothyroxine, oral contraceptives, antiepileptics, and oral antibiotics) — monitoring after dose changes is advisable for warfarin (INR) and levothyroxine (TSH). Anyone enrolling in a CT-388 trial while on chronic medication should disclose all concurrent agents to the trial team.

Safety Profile

Legal Status

Regulatory status changes over time. Verify current local rules with a qualified professional.

Myths & Misconceptions