Fei Gao1, Xiaofeng Lv2, Zhaohui Mo3, Jianhua Ma4, Qiu Zhang5, Gangyi Yang6, Weijuan Liu7, Quanmin Li8, Jian Zhou1, Yuqian Bao1, Weiping Jia1. 1. Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China. 2. Department of Endocrinology and Metabolism, General Hospital of Beijing Military Region, Beijing, China. 3. Department of Endocrinology, The Third Xiangya Hospital, Central South University, Changsha, China. 4. Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China. 5. Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. 6. Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. 7. Department of Endocrinology, Chongqing Three Gorges Central Hospital, Chongqing, China. 8. Department of Endocrinology, The PLA Rocket Force Characteristic Medical Center, Beijing, China.
Abstract
AIM: To assess the efficacy and safety of polyethylene glycol loxenatide (PEX168), a new glucagon-like peptide-1 receptor agonist, as an add-on to metformin therapy in Chinese patients with type 2 diabetes (T2D). MATERIALS AND METHODS: This was a multicentre, randomized, double-blind, placebo-controlled phase 3b trial. After metformin monotherapy (≥1500 mg/day) for 8 weeks or more, patients with uncontrolled T2D (HbA1c of 7.0%-10.5%) from 44 sites were randomized (1:1:1) to metformin + placebo, metformin + PEX168 100 μg, and metformin + PEX168 200 μg. The core treatment period lasted for 24 weeks, followed by a 28-week extension period. The primary endpoint was the change in HbA1c levels at week 24. The main secondary endpoint was the proportion of patients with an HbA1c of less than 7.0% at week 24. RESULTS: The least-square mean (standard error) change in HbA1c levels was significantly greater (P < .001 for superiority) in the PEX168 groups (-1.16% [0.08%] and -1.14% [0.08%] with 100 and 200 μg, respectively) than in the placebo group (0.35% [0.08%]). The proportion of patients with an HbA1c of less than 7.0% at week 24 was significantly higher in the PEX168 100 μg (37.4%) and PEX168 200 μg (40.6%) groups than in the placebo group (16.8%; both P < .001). The gastrointestinal reactions were mild; the risks of hypoglycaemia and weight gain did not increase. Anti-PEX168 antibodies were noted in less than 2% of patients. No treatment-emergent serious adverse events occurred. CONCLUSION: The subcutaneous injection of PEX168 once a week can effectively, continuously and safely improve HbA1c levels in patients with T2D when combined withmetformin.
RCT Entities:
AIM: To assess the efficacy and safety of polyethylene glycol loxenatide (PEX168), a new glucagon-like peptide-1 receptor agonist, as an add-on to metformin therapy in Chinese patients with type 2 diabetes (T2D). MATERIALS AND METHODS: This was a multicentre, randomized, double-blind, placebo-controlled phase 3b trial. After metformin monotherapy (≥1500 mg/day) for 8 weeks or more, patients with uncontrolled T2D (HbA1c of 7.0%-10.5%) from 44 sites were randomized (1:1:1) to metformin + placebo, metformin + PEX168 100 μg, and metformin + PEX168 200 μg. The core treatment period lasted for 24 weeks, followed by a 28-week extension period. The primary endpoint was the change in HbA1c levels at week 24. The main secondary endpoint was the proportion of patients with an HbA1c of less than 7.0% at week 24. RESULTS: The least-square mean (standard error) change in HbA1c levels was significantly greater (P < .001 for superiority) in the PEX168 groups (-1.16% [0.08%] and -1.14% [0.08%] with 100 and 200 μg, respectively) than in the placebo group (0.35% [0.08%]). The proportion of patients with an HbA1c of less than 7.0% at week 24 was significantly higher in the PEX168 100 μg (37.4%) and PEX168 200 μg (40.6%) groups than in the placebo group (16.8%; both P < .001). The gastrointestinal reactions were mild; the risks of hypoglycaemia and weight gain did not increase. Anti-PEX168 antibodies were noted in less than 2% of patients. No treatment-emergent serious adverse events occurred. CONCLUSION: The subcutaneous injection of PEX168 once a week can effectively, continuously and safely improve HbA1c levels in patients with T2D when combined with metformin.