IDF21-0323 Safety and efficacy of IBI362 (LY3305677) in Chinese patients with T2D: A randomized, placebo-controlled phase 1b study

Background: The success of glucagon-like peptide-1 (GLP-1) receptor agonists to treat type 2 diabetes (T2D) and obesity has sparked considerable efforts to develop next-generation co-agonists that are more effective. IBI362 is a novel weekly-dose GLP-1 and glucagon receptor dual agonist that is being developed for the treatment of T2D and obesity. Aim: To evaluate the safety, tolerability, pharmacodynamics and efficacy of IBI362 in Chinese patients with T2D. Method: Patients who had been diagnosed with T2D for at least six months (HbA1c 7.5-11.0% inclusive) that was inadequately controlled with diet and exercise with or without stable metformin therapy were enrolled into three ascending dose cohorts. Patients in each cohort were randomized 8:4:2 to receive once-weekly subcutaneous injection of IBI362 (1.0-2.0-3.0 mg, 1.5-3.0-4.5 mg or 2.0-4.0-6.0 mg), placebo or open-label dulaglutide 1.5 mg for 12 weeks with an 8-week safety follow-up. Primary endpoint was the safety and tolerability of IBI362. Secondary endpoints included changes from baseline in HbA1c and fasting plasma glucose (FPG). Exploratory endpoints included changes from baseline in body weight. This trial was registered with ClinicalTrial.gov, number NCT04466904. Results: Forty-two patients were randomized and received at least one dose of study treatment. Overall, IBI362 was well tolerated and showed a good safety profile. Thirty-eight patients (90.5%) completed the study. One patient receiving IBI362 in the 4.5 mg cohort discontinued the study due to mild decreased appetite. Two patients receiving IBI362 in the 3.0 mg cohort reported serious adverse events of myocardial ischemia, which were unrelated to the study treatment. No severe hypoglycemia was reported. Most commonly reported treatment-emergent adverse events were gastrointestinal adverse events (reported in 11 patients [45.8%] receiving IBI362, two [16.7%] receiving placebo and two [33.3%] receiving dulaglutide) and decreased appetite (reported in six patients [25.0%] receiving IBI362 and one [16.7%] receiving dulaglutide). At week 12, HbA1c, FPG levels and body weight were reduced from baseline in patients receiving IBI362 in all three cohorts (Table). Discussion: IBI362 demonstrated a favorable safety profile and robust efficacy on glycemic control in Chinese patients with T2D.TableEfficacy.IBI362 3.0 mg (N=8)IBI362 4.5 mg (N=8)IBI362 6.0 mg (N=8)Pooled placebo (N=12)Dulaglutide 1.5 mg (N=6)CFB in HbA1c at week12 (%)−1.46 (−2.19, −0.74)−2.23 (−2.96, −1.50)−1.66 (−2.37, −0.95)−0.87 (−1.46, −0.29)−1.98 (−2.80, −1.16)CFB in FPG at week12 (mmol/L)−3.38 (−4.21, −2.55)−3.82 (−4.72, −2.93)−4.07 (−4.88, −3.25)−2.52 (−3.19, −1.85)−3.85 (−4.78, −2.91)Percent CFB in body weight at week12 (%)−0.94 (−3.05, 1.17)−5.03 (−7.21, −2.86)−5.42 (−7.47, −3.37)−1.06 (−2.78, 0.66)−0.87 (−3.25, 1.51)Data are least squares mean (90% confidence interval); CFB = change from baseline; FPG = fasting plasma glucose; HbA1c = hemoglobin A1c. Open table in a new tab Data are least squares mean (90% confidence interval); CFB = change from baseline; FPG = fasting plasma glucose; HbA1c = hemoglobin A1c.