Vanita R Aroda1, Julio Rosenstock2, Carol Wysham3, Jeffrey Unger4, Diego Bellido5, Guillermo González-Gálvez6, Akane Takami7, Hailing Guo8, Elisabeth Niemoeller9, Elisabeth Souhami10, Richard M Bergenstal11. 1. Medstar Health Research Institute, Hyattsville, MD vanita.aroda@medstar.net. 2. Dallas Diabetes Research Center at Medical City, Dallas, TX. 3. Rockwood Clinic, Spokane, WA. 4. Catalina Research Institute, Chino, CA. 5. Complejo Hospitalario Universitario de Ferrol, A Coruña University, A Coruña, Spain. 6. Instituto Jalisciense de Investigación en Diabetes y Obesidad S. C., Universidad de Guadalajara, Hospital Civil de Guadalajara "Dr. Juan I. Menchaca," Guadalajara, Mexico. 7. Sanofi, Tokyo, Japan. 8. Biostatistics, BMD Consulting Inc., Somerset, NJ. 9. Diabetes Division, Sanofi, Frankfurt, Germany. 10. Diabetes Division, Sanofi, Paris, France. 11. International Diabetes Center, Park Nicollet Health Services, Minneapolis, MN.
Abstract
OBJECTIVE: This study was conducted to demonstrate the efficacy and safety of LixiLan (iGlarLixi), a novel, titratable, fixed-ratio combination of insulin glargine (iGlar) (100 units) and lixisenatide, compared with iGlar in patients with type 2 diabetes inadequately controlled on basal insulin with or without up to two oral glucose-lowering agents. RESEARCH DESIGN AND METHODS: After a 6-week run-in when iGlar was introduced and/or further titrated, and oral antidiabetic drugs other than metformin were stopped, 736 basal insulin-treated patients (mean diabetes duration 12 years, BMI 31 kg/m2) were randomized 1:1 to open-label, once-daily iGlarLixi or iGlar, both titrated to fasting plasma glucose <100 mg/dL (<5.6 mmol/L) up to a maximum dose of 60 units/day. The primary outcome was change in HbA1c levels at 30 weeks. RESULTS:HbA1c decreased from 8.5% (69 mmol/mol) to 8.1% (65 mmol/mol) during the run-in period. After randomization, iGlarLixi showed greater reductions in HbA1c from baseline compared with iGlar (-1.1% vs. -0.6%, P < 0.0001), reaching a mean final HbA1c of 6.9% (52 mmol/mol) compared with 7.5% (58 mmol/mol) for iGlar. HbA1c <7.0% (53 mmol/mol) was achieved in 55% of iGlarLixi patients compared with 30% on iGlar. Mean body weight decreased by 0.7 kg with iGlarLixi and increased by 0.7 kg with iGlar (1.4 kg difference, P < 0.0001). Documented symptomatic hypoglycemia (≤70 mg/dL) was comparable between groups. Mild gastrointestinal adverse effects were very low but more frequent with iGlarLixi. CONCLUSIONS: Compared with iGlar, a substantially higher proportion of iGlarLixi-treated patients achieved glycemic targets with a beneficial effect on body weight, no additional risk of hypoglycemia, and low levels of gastrointestinal adverse effects in inadequately controlled, basal insulin-treated, long-standing type 2 diabetes.
RCT Entities:
OBJECTIVE: This study was conducted to demonstrate the efficacy and safety of LixiLan (iGlarLixi), a novel, titratable, fixed-ratio combination of insulinglargine (iGlar) (100 units) and lixisenatide, compared with iGlar in patients with type 2 diabetes inadequately controlled on basal insulin with or without up to two oral glucose-lowering agents. RESEARCH DESIGN AND METHODS: After a 6-week run-in when iGlar was introduced and/or further titrated, and oral antidiabetic drugs other than metformin were stopped, 736 basal insulin-treated patients (mean diabetes duration 12 years, BMI 31 kg/m2) were randomized 1:1 to open-label, once-daily iGlarLixi or iGlar, both titrated to fasting plasma glucose <100 mg/dL (<5.6 mmol/L) up to a maximum dose of 60 units/day. The primary outcome was change in HbA1c levels at 30 weeks. RESULTS: HbA1c decreased from 8.5% (69 mmol/mol) to 8.1% (65 mmol/mol) during the run-in period. After randomization, iGlarLixi showed greater reductions in HbA1c from baseline compared with iGlar (-1.1% vs. -0.6%, P < 0.0001), reaching a mean final HbA1c of 6.9% (52 mmol/mol) compared with 7.5% (58 mmol/mol) for iGlar. HbA1c <7.0% (53 mmol/mol) was achieved in 55% of iGlarLixi patients compared with 30% on iGlar. Mean body weight decreased by 0.7 kg with iGlarLixi and increased by 0.7 kg with iGlar (1.4 kg difference, P < 0.0001). Documented symptomatic hypoglycemia (≤70 mg/dL) was comparable between groups. Mild gastrointestinal adverse effects were very low but more frequent with iGlarLixi. CONCLUSIONS: Compared with iGlar, a substantially higher proportion of iGlarLixi-treated patients achieved glycemic targets with a beneficial effect on body weight, no additional risk of hypoglycemia, and low levels of gastrointestinal adverse effects in inadequately controlled, basal insulin-treated, long-standing type 2 diabetes.
Authors: Ofri Mosenzon; Stefano Del Prato; Meir Schechter; Lawrence A Leiter; Antonio Ceriello; Ralph A DeFronzo; Itamar Raz Journal: Cardiovasc Diabetol Date: 2021-04-28 Impact factor: 9.951
Authors: Melanie J Davies; David A D'Alessio; Judith Fradkin; Walter N Kernan; Chantal Mathieu; Geltrude Mingrone; Peter Rossing; Apostolos Tsapas; Deborah J Wexler; John B Buse Journal: Diabetologia Date: 2018-12 Impact factor: 10.122