RO7795068
Evidence Grade E — Very limited evidence. 2 published studies. 5 registered clinical trials.
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.
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.
A Clinical Study to Evaluate the Effects of RO7795068 in Participants With Obesity or Overweight and Type 2 Diabetes
A Clinical Study to Evaluate the Effects of RO7795068 in Participants With Obesity or Overweight Without Type 2 Diabetes
A Study of CT-388 in Participants Who Are Overweight or Obese With Type 2 Diabetes Mellitus
A Study of 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
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Liraglutide is marketed as Victoza for type 2 diabetes (approved 2010) and Saxenda for weight management (approved 2014). The LEADER trial, involving over 9,300 patients followed for nearly four years, established that liraglutide reduced the risk of major cardiovascular events by 13% — a landmark finding that helped establish GLP-1 treatments as a class with heart benefits. Saxenda is also approved for adolescents aged 12 and older. While historically significant, liraglutide has been substantially surpassed by newer agents. In a direct comparison, semaglutide achieved 15.8% weight loss compared to liraglutide's 6.4%. Liraglutide remains relevant as a lower-intensity option and as a benchmark against which newer treatments are measured. It has over a decade of real-world safety data, making it one of the best-understood medications in this class.
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.
HGH Fragment 176-191 has no marketing authorisation. A Phase IIa trial in obesity (approximately 300 patients) failed to demonstrate statistically significant weight loss at any dose tested. The clinical development programme was discontinued. The disconnect between animal data (which showed significant fat reduction in obese mice) and the failed human trial is the defining feature of this compound's development history. Products available through unregulated channels lack pharmaceutical quality assurance. The failed Phase II trial represents the highest level of clinical evidence available.
