Evidence Grade E — Very limited evidence. 2 published studies. 6 registered clinical trials.
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CT-388 is a dual GIP/GLP-1 receptor agonist originally developed by Carmot Therapeutics, which was acquired by Roche for $2.7 billion. Now in Phase II/III development, it is engineered with a specific signalling bias designed to keep receptors responsive for longer, which may improve both effectiveness and tolerability. Phase II results showed 22.5% weight loss with notably low dropout rates.
CT-388 is also known by these brand and alternate names:
2 published studies: 2 human, 0 animal, 0 in-vitro, 1 reviews
CT-388 is in Phase II/III development (not yet approved). Phase II results (469 patients, 48 weeks) showed 22.5% placebo-adjusted weight loss at the highest dose, with low discontinuation rates due to adverse events (5.9%). Phase III trials are underway.
The combination of high efficacy and low discontinuation rates in Phase II is notable — many obesity drugs achieve high weight loss but suffer from tolerability-driven dropouts. Roche's $2.7 billion acquisition of the developer signals significant confidence in the programme.
CT-388 activates both GIP and GLP-1 receptors with a deliberate signalling bias toward cAMP production while minimising beta-arrestin recruitment. This biased agonism theoretically keeps receptors available at the cell surface for longer, potentially sustaining drug effect and reducing side effects caused by receptor overstimulation. The approach is similar in concept to ecnoglutide (#168) but applied to a dual-receptor agonist.
Phase II results (469 patients, 48 weeks) showed 22.5% placebo-adjusted weight loss at the highest dose, with only 5.9% discontinuing due to side effects — a notably low rate for an obesity treatment achieving this level of efficacy. Over a quarter of participants lost at least 30% of their body weight. Phase III trials (the Enith programme) began in early 2026, with results expected around 2028. Roche is also exploring a combination of CT-388 with the amylin analogue petrelintide. The combination of high efficacy and low discontinuation rates in Phase II is the key differentiator, though Phase III confirmation is needed. The competitive landscape for GIP/GLP-1 dual agonists is intensifying rapidly.
PeptideTrace tracks 6 registered clinical trials for CT-388 sourced from ClinicalTrials.gov.
A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Enicepatide in Generally Healthy Adult Chinese Participants
A Clinical Study to Evaluate the Effects of Enicepatide (RO7795068) in Participants With Obesity or Overweight and Type 2 Diabetes
A Clinical Study to Evaluate the Effects of Enicepatide (RO7795068) in Participants With Obesity or Overweight Without Type 2 Diabetes
A Study of Enicepatide (CT-388) in Participants Who Are Overweight or Obese With Type 2 Diabetes Mellitus
A Study of Enicepatide (CT-388) in Participants With Obesity or Overweight With at Least One Weight-Related Comorbidity
CT-388 (RO7795068) is a synthetic 34-residue dual GLP-1/GIP receptor agonist peptide with molecular weight 4,825.4 Da and molecular formula C226H345FN48O67. Developed by Carmot Therapeutics, which was acquired by Roche in December 2023 for $2.7 billion upfront plus up to $400 million in milestones. Now developed under Genentech. IMPORTANT: CT-388 is a dual GLP-1/GIP agonist, NOT a triple agonist as initially reported. The compound was designed for cAMP-biased signaling with minimal beta-arrestin recruitment.
CT-388 functions as a biased dual agonist at both GLP-1R and GIPR, engineered for preferential cAMP signaling with minimal beta-arrestin recruitment at both target receptors. This signaling bias theoretically prolongs pharmacological activity by reducing receptor internalization and desensitization, potentially improving the therapeutic window. Once-weekly subcutaneous dosing is supported by the peptide's pharmacokinetic profile.
Phase 2 (NCT06525935; N=469; topline January 2026): the 24 mg dose produced placebo-adjusted weight loss of 22.5% at 48 weeks (efficacy estimand; P<0.001); treatment-regimen estimand: 18.3%. Categorical outcomes at 24 mg: at least 10% loss in 87%, at least 20% in 47.8%, at least 30% in 26.1%. Discontinuation due to adverse events: 5.9%. Phase 1b extension (N=31): placebo-adjusted -18.8 to -18.9% at 24 weeks. Phase 3 trials (Enith1 and Enith2) were initiated Q1 2026. In March 2025, Roche partnered with Zealand Pharma ($1.65 billion) to co-develop a petrelintide plus CT-388 fixed-dose combination.
The information on this page is provided for educational and research reference purposes only. This is not medical advice. Always consult a qualified healthcare professional before making any health-related decisions.
Semaglutide is one of the most extensively studied peptide medications available today, with clinical trial data spanning over 50,000 patients. It is sold as Ozempic for type 2 diabetes (approved 2017), Rybelsus as an oral tablet for diabetes (approved 2019), and Wegovy for weight management (approved 2021). Wegovy has since received additional approvals for reducing heart attack and stroke risk, for use in adolescents aged 12 and older, and for liver disease related to obesity. In clinical trials, patients taking Wegovy lost an average of 14.9% of their body weight over 68 weeks, and the SELECT trial demonstrated a 20% reduction in major cardiovascular events such as heart attack and stroke. Research is now exploring its potential in early Alzheimer's disease. The main side effects are gastrointestinal, particularly nausea, and a key limitation is that most weight tends to return after stopping treatment.
Bimagrumab is in Phase II/III development (not yet approved). A Phase II trial (75 patients with type 2 diabetes and obesity) showed 20.5% fat mass reduction with 3.6% lean mass increase — essentially reshaping body composition without net appetite suppression. The BELIEVE Phase IIb trial (507 patients) showed that bimagrumab plus semaglutide achieved 22% weight loss with the weight lost being 88% fat — significantly better body composition than semaglutide alone. Bimagrumab is not a peptide. Its strategic significance is as a combination partner to address the muscle loss problem inherent in weight loss with current obesity drugs. Eli Lilly's acquisition positions it alongside tirzepatide.
Pemvidutide is in Phase II/III development (not yet approved). In the MOMENTUM Phase II trial (391 patients, 48 weeks), the 2.4 mg dose achieved 15.6% weight loss. Body composition analysis showed 78% of weight lost was fat mass, with only 22% lean mass — a favourable ratio. A Phase IIb MASH trial (212 patients) showed MASH resolution in up to 75% of patients at the highest dose. Pemvidutide's balanced receptor profile and no-titration dosing regimen represent potential practical advantages. The high rate of MASH resolution in Phase II positions it as a candidate for liver disease indications alongside obesity.
Evidence Reviews
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
