Summary: At the 86th ADA Scientific Sessions in early June 2026, Roche/Genentech presented detailed late-breaking Phase 2 data for enicepatide, the dual GLP-1/GIP receptor agonist peptide formerly known as CT-388. The 48-week CT388-103 trial in 469 adults with obesity hit 22.5% placebo-adjusted weight loss at the 24 mg once-weekly dose, with 54% of treated participants resolving obesity (BMI under 30) and — notably — no weight-loss plateau at study end. Two global Phase 3 trials have been recruiting since March 2026.
The numbers put enicepatide in the same conversation as tirzepatide and retatrutide. The question for the next 18 months is whether biased agonism — the design feature Roche has emphasized — translates into a durable head-to-head advantage in Phase 3.
The headline data from CT388-103
Roche presented detailed Phase 2 CT388-103 data at ADA 2026 in a late-breaking poster session on June 7 and a satellite symposium on June 8, expanding on the January 27, 2026 topline. The 48-week multi-center, randomized, double-blind, placebo-controlled trial enrolled 469 adults with obesity (BMI 30 or above) or overweight (BMI 27 to under 30) plus a weight-related comorbidity, excluding people with type 2 diabetes. Participants were randomized across five dosing cohorts up to a 24 mg once-weekly maintenance dose.
At the 24 mg dose, the trial reported placebo-adjusted weight loss of 22.5% by the efficacy estimand (which captures the on-treatment effect) and 18.3% by the treatment-regimen estimand (which counts dropouts and treatment switches as zero). Both readouts were highly statistically significant (p < 0.001). At week 48, 95.7% of treated participants achieved at least 5% weight loss, 87% achieved at least 10%, 47.8% achieved at least 20%, and 26.1% achieved at least 30%. 54% of participants on the 24 mg dose reached BMI under 30, a measure Roche described as "resolution of obesity," compared with 13% in the placebo group. 73% of baseline-prediabetic participants on the 24 mg dose returned to normal glucose levels at week 48 versus 7.5% on placebo.
What stands out in the curves: weight loss had not plateaued at week 48. The trajectory was still descending, which suggests the 24 mg dose was not yet at its biological ceiling in this population.
Tolerability was class-consistent. Adverse events were mostly mild-to-moderate gastrointestinal — nausea, diarrhea, vomiting — with low rates of severe events. Treatment-related discontinuation was 5.9% in pooled CT-388 arms versus 1.3% in placebo. By comparison, tirzepatide trials have reported class-norm discontinuation rates closer to 10-15%. The full trial details are registered at ClinicalTrials.gov NCT06525935.
Biased agonism: what Roche is betting on
Enicepatide is engineered as a unimolecular peptide dual agonist of the GLP-1 receptor (GLP-1R) and the glucose-dependent insulinotropic polypeptide receptor (GIPR). Both receptors are class B GPCRs that, when activated by their native ligands, signal through Gαs to raise intracellular cAMP. They also recruit beta-arrestin, which drives receptor internalization and desensitization.
The molecule was designed to be a cAMP-signal-biased agonist — meaning it triggers strong cAMP signaling at both receptors but recruits little beta-arrestin at either. In cell-based assays and animal models published in Molecular Metabolism (2026), this bias profile produced minimal receptor internalization compared with native ligands, supporting sustained signaling over time. In Phase 1 (NCT04838405), four weekly doses produced 4.7% to 8.0% weight loss across the dose range at day 29, with a tolerability profile consistent with the incretin class.
The clinical hope is that biased agonism produces more durable receptor engagement and therefore more durable weight loss, with fewer tolerability problems caused by acute peak signaling. The CT388-103 data — no plateau at 48 weeks, comparatively low discontinuation — are consistent with that hope. Phase 3 will test it across a much larger population and a longer time horizon.
The Phase 3 program: what it tests and when
Two Phase 3 trials have been recruiting since March 2026.
NCT07351045 is a once-weekly enicepatide trial in adults with obesity or overweight plus a comorbidity, without type 2 diabetes. The primary endpoint is percent change in body weight from baseline to week 72, with multiple secondary endpoints covering glycemic, cardiometabolic, and quality-of-life measures. NCT07351058 is the parallel T2D trial. Both use an integrated drug-device combination product for subcutaneous self-administration.
The week-72 endpoint is longer than many GLP-1 Phase 3 trials, which is a tell about Roche's expectations. Tirzepatide's SURMOUNT-1 used week-72 in its primary endpoint as well, and the 22.5% Phase 2 placebo-adjusted number at week 48 leaves room for the trajectory to keep going to week 72 if the no-plateau pattern holds. Top-line readouts are not expected before 2027 at the earliest, given the enrollment and follow-up timeline.
Petrelintide combination: the next bet
The other piece of Roche's obesity portfolio announced at ADA 2026 is petrelintide, the long-acting amylin analog peptide Roche licensed from Zealand Pharma in 2024. Late-breaking ZUPREME-1 Phase 2 data presented at ADA showed meaningful weight loss with what Roche framed as a compelling tolerability profile — the amylin mechanism produces satiety signaling without the heavy GLP-1-related GI side-effect burden.
The strategic logic is straightforward. If you can pair a dual GLP-1/GIP agonist with an amylin agonist, you can stack mechanisms that target appetite and satiety through different receptor systems. The combination should produce additive weight loss while distributing the side-effect burden — the GI tolerability ceiling on GLP-1-only regimens stops being the bottleneck. A Phase 2 fixed-dose combination study of enicepatide plus petrelintide is targeted to enroll its first patient around mid-2026.
For reference, Novo Nordisk's CagriSema (cagrilintide plus semaglutide) and Eli Lilly's amylin and triple-agonist programs are pursuing variations of the same combination thesis. If any of them work, the late-2020s obesity therapy landscape is fixed-dose combinations rather than higher-dose monotherapies.
What could go wrong between now and Phase 3 readout
Three concrete risks deserve naming. The first is dose tolerability over a longer window. Phase 2 had a 48-week observation; Phase 3 goes to 72. The discontinuation signal at 5.9% is favorable in absolute terms, but the people who dropped out tended to drop out earlier in titration. Whether the patients who stay on 24 mg through week 72 maintain that tolerability is a different question.
The second is the placebo-adjusted gap. The reason the 22.5% figure looks so strong is that it is placebo-adjusted, and the placebo group in CT388-103 lost a few percent on its own. Phase 3 with a larger and more heterogeneous population may produce a larger placebo response, narrowing the gap.
The third is the no-plateau observation. It is genuinely notable, but it is also based on one trial in one population. If the curve plateaus between weeks 48 and 72 in Phase 3, the headline number compresses.
Commercial and clinical context
The current standard of care for chronic weight management in the U.S. is anchored by semaglutide (Wegovy), tirzepatide (Zepbound), and the newly approved oral GLP-1 orforglipron (Foundayo, approved April 1, 2026). Retatrutide — Eli Lilly's GLP-1/GIP/glucagon triple agonist — reported 28.3% Phase 3 weight loss at 80 weeks on May 21, 2026, but is not yet filed. Pfizer's once-monthly berobenatide presented detailed Phase 2b data at ADA on June 8.
Against that field, the enicepatide value proposition is specific: best-in-class Phase 2 placebo-adjusted weight loss for a dual agonist, low discontinuation rate, a combination strategy with petrelintide, and Roche's commercial muscle behind it. The risk is that Phase 3 produces a smaller separation than Phase 2, that the no-plateau signal at 48 weeks does not extend through 72 weeks, or that everyday clinical tolerability differs from trial tolerability.
For clinicians and patients, the practical timeline is 18-24 months out at the earliest. Phase 3 will define whether enicepatide enters a market with three approved injectable GLP-1 options or whether the combination story changes the calculus entirely.
Frequently Asked Questions
What is enicepatide?
Enicepatide is the International Nonproprietary Name for the investigational dual GLP-1/GIP receptor agonist peptide previously known as CT-388 and RO7795068. It is developed by Roche/Genentech (acquired from Carmot Therapeutics in 2024) for chronic weight management and type 2 diabetes.
How does enicepatide compare to tirzepatide?
Both are dual GLP-1/GIP agonists, but enicepatide is engineered as a cAMP-biased agonist with minimal beta-arrestin recruitment — a design intended to reduce receptor internalization and sustain signaling. Phase 2 placebo-adjusted weight loss was 22.5% at 48 weeks; tirzepatide's SURMOUNT-1 reported around 17.8% placebo-adjusted at 72 weeks. Direct head-to-head trials have not been conducted.
When will Phase 3 data be available?
Two global Phase 3 trials (NCT07351045 in obesity, NCT07351058 in T2D) have been recruiting since March 2026 and use a 72-week primary endpoint. Top-line readouts are not expected before 2027 at the earliest.
Is enicepatide FDA-approved?
No. As of June 2026 enicepatide is investigational and not yet approved by any regulator. Phase 3 trials are ongoing.
What is the petrelintide combination about?
Petrelintide is Roche's once-weekly amylin analog (originally Zealand Pharma). The plan is a Phase 2 fixed-dose combination of enicepatide plus petrelintide, with the first patient expected to enroll around mid-2026. The thesis is that pairing GLP-1/GIP agonism with amylin agonism could produce additive weight loss while distributing side effects across mechanisms.
Sources
- Roche ADA 2026 portfolio announcement (June 1, 2026)
- Roche Phase II topline results for CT-388 (January 27, 2026)
- Chakravarthy MV et al, "Effects of CT-388, a once-weekly signaling-biased dual GLP-1/GIP receptor agonist" (Mol Metab 2026)
- Phase 2 CT388-103 trial (ClinicalTrials.gov NCT06525935)
- Phase 3 obesity trial NCT07351045
Sources & References
- FDA PCAC Meeting Announcement (July 23-24, 2026)
- PBS: FDA to Weigh Easing Limits on Peptides Favored by RFK Jr.
- BioPharma Dive: FDA Peptides RFK Advisory Committee Restrictions
- RAPS: FDA Considers Adding a Dozen Peptides to Bulk Drug List
- Ars Technica: RFK Jr. Forces FDA to Reconsider 12 Peptides
- ProPublica: Peptide Safety Investigation
- New York Times: Peptide Ban FDA RFK Jr.
- SSRP Institute: FDA Announces Change in Status of 12 Peptides
- CNBC: RFK Jr. Peptides Hims Hers GLP-1
- USA Today: RFK Jr. FDA Peptides Explainer
