Effectiveness and safety of CT-868, a new drug activating two blood sugar hormones, in type 2 diabetes: A double-blind, placebo-controlled phase 2 trial
CT-868 led to clinically significant reductions in of -1.61 to -2.24 percentage points compared to placebo at 26 weeks.
Participants receiving CT-868 showed statistically significant improvements in HbA1c compared to those on placebo (all p < 0.001).
Body weight decreased modestly with CT-868 4.0 mg, showing a reduction of -2.9% compared to placebo (p < 0.001).
CT-868 improved fasting glucose levels, self-monitored blood glucose, and most lipid measurements compared to placebo.
Adverse events were mostly mild to moderate, with no occurrences of hypoglycaemia reported.
Simplified
AIMS: To assess the glycaemic efficacy and safety of CT-868, a cAMP signal-biased, dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor agonist, in participants with type 2 diabetes (T2D).
MATERIALS AND METHODS: This 26-week (W), phase 2, randomized, double-blind placebo-controlled trial enrolled adults with T2D, Body Mass Index ≥27 kg/m, and glycated haemoglobin () 7.0-10.0%. Participants were randomized (1:2:1) to once-daily CT-868 1.75 mg, 4.0 mg, or placebo. Due to COVID-19-related CT-868 supply constraints, some participants randomized to 4.0 mg received 3.25 mg maximum and were analysed as a separate dose arm. The primary endpoint was change from baseline in HbA1c at W26. Secondary endpoints included changes from baseline to W26 in fasting glucose, 7-point self-monitored blood glucose (SMBG), body weight, lipids and the occurrence of adverse events (AEs). 2
RESULTS: Overall, 103 participants were enrolled (CT-868 1.75 mg, n = 26; 3.25 mg, n = 18; 4.0 mg, n = 32; placebo, n = 27). Clinically meaningful and statistically significant improvements in HbA1c were observed with CT-868 at W26 (-1.61 to -2.24%-points vs. placebo; all p < 0.001). Body weight was modestly reduced with CT-868 4.0 mg at W26 (-2.9% vs. placebo, p < 0.001). CT-868 improved fasting glucose, SMBG, and most lipid parameters vs. placebo. AEs were mostly mild/moderate. No participants experienced hypoglycaemia.
CONCLUSIONS: CT-868 1.75 to 4.0 mg yielded robust, clinically meaningful decreases in HbA1c, supporting potent glycaemic-lowering effects and improved key lipid parameters in participants with overweight/obesity and T2D, despite modest weight loss. CT-868 was well tolerated, supporting future investigation of higher doses to maximize weight loss.
Key numbers
-1.61 to -2.24%-points
Reduction
Change in levels at Week 26 vs. placebo
-2.9%
Body Weight Change
Percent change in body weight at Week 26 vs. placebo
80.8%
Adverse Events
Percentage of participants with any TEAE
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Manu V. Chakravarthy, Luis Acosta, Gabriele E. Sonnenberg, Damian Bialonczyk, and Jingtao Wu are full‐time employees of Roche (previously Carmot Therapeutics) and may hold Roche stock and/or stock options. Michael A. Elliott is a former employee of Carmot Therapeutics (now Roche). Federico A. Argüelles‐Tello, Raymundo Garcia‐Reza, and José Gerardo González‐González are employees of Avant‐Santé, which has a consulting agreement with Carmot/Roche. Stig K. Hansen is a former employee of Carmot Therapeutics (now Roche) and a current employee of Kimia Therapeutics. Juan P. Frias is also an employee of Biomea Fusion Inc. and has a consulting agreement with Carmot/Roche.
