Roche's Novel Dual GLP-1/GIP Receptor Agonist Produces Clinically Meaningful Weight Loss in Phase Ib Trial

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Roche’s dual GLP-1/GIP receptor agonist CT-388 produced positive findings treating obesity and type 2 diabetes in Phase Ib clinical trial.1 The company announced results from the trial show that a once-weekly subcutaneous (SC) injection of CT-388 produced significant weight loss in healthy adults with obesity compared with placebo across 24 weeks.¹

“We are very pleased to see the significant and clinically meaningful weight loss in people treated with CT-388,” Levi Garraway, MD, PhD, Roche chief medical officer and head of Global Product Development, said in a press release. “The results are highly encouraging for further development of CT-388 for both obesity and type 2 diabetes and underscore its potential to become a best-in-class therapy with durable weight loss and glucose control.”¹

GLP-1s were identified as therapeutic agents in 2005 and were initially approved for lowering blood sugar in patients with diabetes. However, in the years that followed, clinical trials have shown their efficacy in weight loss and improving cardiovascular outcomes among these patients.^2,3

GLP-1 receptor agonists replace endogenous hormones to stimulate pancreatic islet cells, which leads to increased release of glucose-dependent insulin. The drug class has also been found to slow gastric emptying, lower post-meal glucagon release, and increase satiety.

A once-weekly SC injectable, CT-388 is a dual GLP-1/GIP receptor agonist designed to produce potent activity on both the GLP-1 and GIP receptors, along with minimal to no ß-arrestin recruitment on either receptor. CT-388 is currently being evaluated in a multi-part, multi-cohort Phase I clinical trial in patients with overweight/obesity with and without type 2 diabetes.

The multi-arm, multi-cohort, Phase Ib, randomized, double-blind, placebo-controlled CT-388-101 trial analyzed the safety, tolerability, pharmacokinetics, and pharmacodynamics of CT-388 in adults with overweight or obesity and in adults with obesity and type 2 diabetes mellitus, who are otherwise healthy. The trial’s primary endpoint was the safety and tolerability of CT-388, with secondary endpoints that included effect on body weight and glucose homeostasis. Investigators also evaluated the pharmacokinetics and pharmacodynamic effects of CT-388.

The weight loss observed among patients administered CT-388 was deemed clinically meaningful, with a mean placebo-adjusted weight loss of 18.8% (p-value < 0.001). At week 24, 100% of participants administered CT-388 achieved a weight loss of >5%, 85% achieved >10%, 70% achieved >15%, and 45% achieved >20%. In terms of safety, CT-388 was found to be well tolerated. The most commonly reported adverse events (AEs) among patients administered the novel therapy were mild to moderate gastrointestinal-related AEs.

All patients with a pre-diabetes status at baseline became normoglycemic following 24 weeks of treatment with CT-388. Meanwhile, the glycemic status of patients in the placebo cohort was largely unchanged during the trial.

Roche stated that it anticipates data from an additional cohort from the ongoing placebo-controlled Phase Ib trial of CT-388 among obese patients (BMI>30 kg/m2) with type 2 diabetes across a 12-week treatment duration in the second half of 2024.

References

1. Roche reports positive Phase Ib results for its dual GLP-1/GIP receptor agonist CT-388 in people with obesity. News release. Roche. May 15, 2024. Accessed May 16, 2024. https://www.roche.com/media/releases/med-cor-2024-05-16

2. Rahman A, Alqaisi S, Saith SE, Alzakhari R, Levy R. The Impact of Glucagon-Like Peptide-1 Receptor Agonist on the Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus: A Meta-Analysis and Systematic Review. Cardiol Res. 2023;14(4):250-260. doi:10.14740/cr1523

3. Hinnen D. Glucagon-like peptide 1 receptor agonists for type 2 diabetes. Diabetes Spectrum. 2017;30(3):202-210. doi:10.2337/ds16-0026