This randomized, double-blind, placebo-controlled multiple-ascending-dose phase 1b study evaluated the safety, tolerability and pharmacokinetics/ pharmacodynamics of IBI362 in Chinese patients with type 2 diabetes, with dulaglutide as an active control. Fourteen patients were enrolled in each of the three cohorts and randomized 8:4:2 to receive once weekly IBI362, placebo or 1.5 mg dulaglutide subcutaneously for 12 weeks. Dose escalation regimens for IBI362 and placebo were 1.0-2.0-3.0 mg (cohort 1), 1.5-3.0-4.5 mg (cohort 2) or 2.0-4.0-6.0 mg (cohort 3), with each dose level administered for 4 weeks. IBI362 was well tolerated and showed a safety profile comparable to dulaglutide. Gastrointestinal adverse events and decreased appetite were the most commonly-reported adverse events, mostly transient and mild in severity. At week 12, mean changes from baseline in HbA1c levels were −1.46%, −2.23% and −1.66% for patients receiving IBI362 in cohort 1,2 and 3, respectively (−1.98% for dulaglutide). Given the variations brought by limited sample size, after removing patients with maximum and minimum changes from baseline to week 12 in HbA1c in each dose group, the adjusted mean changes from baseline in HbA1c levels were −1.46%, −2.28% and −1.87% for patients receiving IBI362 in cohort 1,2 and 3, respectively (−1.46% for dulaglutide). Meanwhile, mean percent changes from baseline to week 12 in body weight were −0.9%，−5.0% and −5.4% for patients receiving IBI362 in cohort 1,2 and 3, respectively (−0.9% for dulaglutide). Improvements in waist circumference, body mass index, blood pressure and lipid levels were observed in patients receiving IBI362, with overall trends similar with those observed in phase 1b study in participants with overweight or obesity.
Professor Wenying Yang of China-Japan Friendship Hospital, primary investigator of the study, stated: “In recent years, GLP-1 receptor agonists have demonstrated weight loss and cardio-renal benefits to patients with diabetes while achieving glycemic control, delivering broad application prospect. We are delighted to see that IBI362, as a novel dual GLP-1 receptor and glucagon receptor agonist, has shown a favorable safety profile in Chinese patients with type 2 diabetes, together with multiple benefits of glycemic control, weight loss and metabolic profiles. These results showed the great advantage of IBI362 as a next generation GLP-1 dual agonist over mono-agonists. I am confident in the future clinical development of IBI362, and believe that IBI362 will continue to demonstrate impressive results and bring further clinical benefits in the ongoing phase II clinical trial with larger sample size and longer study duration.”
Dr. Lei Qian, Executive Director of Innovent, stated: “In addition to the glycemic control efficacy of GLP-1 receptor agonism, IBI362, as a dual GLP-1 receptor and glucagon receptor agonist, may be able to promote energy expenditure by activating glucagon receptor, achieve prolonged and more pronounced weight loss compared to selective GLP-1 receptor agonists, and bring multiple metabolic benefits to patients with type 2 diabetes. Substantial weight loss has also been observed in the phase 1b clinical study of IBI362 in participants with overweight or obesity. In this 12-week phase 1b study in Chinese patients with type 2 diabetes, IBI362 showed favorable safety, significant glycemic control and weight loss, with comprehensive benefits on blood pressure, lipid levels and liver enzymes generally similar to the trends observed in the previous clinical study. We look forward to witness more robust results in subsequent clinical studies.”