Evidence Grade E — Very limited evidence. 2 published studies. 5 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 5 registered clinical trials for CT-388 sourced from ClinicalTrials.gov.
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
A Study of CT-388 in Otherwise Healthy Overweight and Obese Adults and Patients With Type 2 Diabetes Mellitus
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.
Danuglipron's original twice-daily formulation achieved 8–13% weight loss in Phase IIb but with treatment discontinuation rates exceeding 50%, with nausea affecting up to 73% of patients. Pfizer discontinued the twice-daily formulation and is developing a once-daily modified-release version. Danuglipron is not a peptide. Its development trajectory illustrates that even effective weight loss compounds can fail commercially if tolerability is inadequate. The reformulation effort aims to reduce peak drug concentrations that likely drive the gastrointestinal side effects.
Setmelanotide is marketed as Imcivree (Rhythm Pharmaceuticals; approved November 2020 for POMC, PCSK1, or LEPR deficiency; June 2022 for Bardet-Biedl syndrome; December 2024 expanded to patients aged 2 years and older). Genetic testing confirming an eligible mutation is required before treatment. In patients with POMC or PCSK1 deficiency, approximately 80% achieved at least 10% weight loss in clinical trials. In Bardet-Biedl syndrome, 32.3% achieved the same threshold. The most common side effects are injection-site reactions and skin darkening (due to the melanocortin pathway's connection to pigmentation). Setmelanotide exemplifies precision medicine — it is highly effective in the specific genetic populations it targets but is not indicated for common obesity.
Amycretin is in early-phase development (not yet approved). The oral formulation achieved 13.1% weight loss at just 12 weeks — substantially faster than existing oral options. The subcutaneous formulation achieved 24.3% at 36 weeks. Both results are from Phase I/II trials with relatively small patient numbers. Amycretin's significance lies in its oral formulation achieving weight loss approaching injectable drugs. If the early results are confirmed in larger trials, an effective oral dual-agonist could significantly expand the obesity treatment population. Phase III trials are anticipated.
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.
