Julio Rosenstock1, Markolf Hanefeld2, Paramesh Shamanna3, Kyung Wan Min4, Gabor Boka5, Patrick Miossec6, Tianyue Zhou7, Isabel Muehlen-Bartmer8, Robert E Ratner9. 1. Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX, USA. Electronic address: JulioRosenstock@DallasDiabetes.com. 2. Centre for Clinical Studies, GWT-TUD GmbH, Dresden, Germany. 3. Bangalore Diabetes Centre, Bangalore, India. 4. Eulji General Hospital, Seoul, Republic of Korea. 5. Sanofi R&D, Chilly-Mazarin, France. 6. Sanofi R&D, Paris, France. 7. Sanofi, Bridgewater, NJ, USA. 8. Sanofi R&D, Frankfurt, Germany. 9. Medstar Health Research Institute and Georgetown University Medical School, Washington, DC, USA.
Abstract
AIMS: To assess efficacy and safety of lixisenatide once-daily versus placebo in type 2 diabetes mellitus (T2DM) patients inadequately controlled onsulfonylurea (SU) ± metformin. METHODS: In this randomized, double-blind, two-arm, parallel-group, multicenter study, patients received lixisenatide 20 μg once-daily or placebo for 24 weeks in a stepwise dose increase on top of SUs ± metformin. Primary outcome was change in HbA1c from baseline to Week 24. RESULTS: Lixisenatide provided a significant reduction in HbA1c at Week 24 versus placebo (LS mean: -0.85% vs. -0.10%; p<0.0001) and more patients achieved HbA1c <7.0% (36.4% vs. 13.5%; p<0.0001). Lixisenatide significantly lowered FPG and body weight versus placebo. In breakfast meal test patients, lixisenatide reduced 2-hour PPG versus placebo (LS mean: -111.48 vs. -3.80 mg/dL [-6.19 vs. -0.21 mmol/L]; p<0.0001) and glucose excursion (-94.11 vs. +6.24 mg/dL [-5.22 vs. +0.35 mmol/L]), and reduced 2-hour glucagon, insulin, proinsulin, and C-peptide. The percentage of AEs was 68.3% for lixisenatide and 61.1% for placebo; and for SAEs: 3.5% versus 5.6%, respectively. Lixisenatide did not significantly increase symptomatic hypoglycemia versus placebo (15.3% vs. 12.3%, respectively); one severe episode of hypoglycemia was reported with lixisenatide. CONCLUSIONS:Once-daily lixisenatide significantly improved glycemic control, with a pronounced postprandial effect, without significant increase in symptomatic/severe hypoglycemia risk and with weight loss over 24 weeks.
RCT Entities:
AIMS: To assess efficacy and safety of lixisenatide once-daily versus placebo in type 2 diabetes mellitus (T2DM) patients inadequately controlled on sulfonylurea (SU) ± metformin. METHODS: In this randomized, double-blind, two-arm, parallel-group, multicenter study, patients received lixisenatide 20 μg once-daily or placebo for 24 weeks in a stepwise dose increase on top of SUs ± metformin. Primary outcome was change in HbA1c from baseline to Week 24. RESULTS:Lixisenatide provided a significant reduction in HbA1c at Week 24 versus placebo (LS mean: -0.85% vs. -0.10%; p<0.0001) and more patients achieved HbA1c <7.0% (36.4% vs. 13.5%; p<0.0001). Lixisenatide significantly lowered FPG and body weight versus placebo. In breakfast meal test patients, lixisenatide reduced 2-hour PPG versus placebo (LS mean: -111.48 vs. -3.80 mg/dL [-6.19 vs. -0.21 mmol/L]; p<0.0001) and glucose excursion (-94.11 vs. +6.24 mg/dL [-5.22 vs. +0.35 mmol/L]), and reduced 2-hour glucagon, insulin, proinsulin, and C-peptide. The percentage of AEs was 68.3% for lixisenatide and 61.1% for placebo; and for SAEs: 3.5% versus 5.6%, respectively. Lixisenatide did not significantly increase symptomatic hypoglycemia versus placebo (15.3% vs. 12.3%, respectively); one severe episode of hypoglycemia was reported with lixisenatide. CONCLUSIONS: Once-daily lixisenatide significantly improved glycemic control, with a pronounced postprandial effect, without significant increase in symptomatic/severe hypoglycemia risk and with weight loss over 24 weeks.