Julio Rosenstock1, Bruno Guerci2, Markolf Hanefeld3, Sandro Gentile4, Ronnie Aronson5, Francisco J Tinahones6, Christine Roy-Duval7, Elisabeth Souhami7, Marek Wardecki8, Jenny Ye9, Riccardo Perfetti9, Simon Heller10. 1. Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX juliorosenstock@dallasdiabetes.com. 2. University of Lorraine and the Department of Diabetology, Metabolic Diseases and Nutrition, Brabois Adult Hospital, Vandœuvre-lès-Nancy, France. 3. GWT-TUD, Study Centre Prof. Hanefeld, Dresden Technical University, Dresden, Germany. 4. Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy. 5. LMC Diabetes & Endocrinology, Toronto, Ontario, Canada. 6. Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Carlos III Institute of Health and Hospital Virgen de la Victoria, Malaga, Spain. 7. Sanofi, Paris, France. 8. Sanofi, Warsaw, Poland. 9. Sanofi, Bridgewater, NJ. 10. Academic Unit of Diabetes, Endocrinology and Metabolism, University of Sheffield, Sheffield, U.K.
Abstract
OBJECTIVE: To provide evidence-based options on how to intensify basal insulin, we explored head-to-head prandial interventions in overweight patients with type 2 diabetes inadequately controlled on basal insulin glargine with or without 1-3 oral antidiabetic agents (OADs). RESEARCH DESIGN AND METHODS: Patients were randomized to lixisenatide once daily or insulin glulisine given once or thrice daily, added to glargine, with or without metformin, if HbA1c remained ≥7 to ≤9% (≥53 to ≤75 mmol/mol) after 12 weeks of glargine optimization with OADs other than metformin stopped at the start of optimization. Coprimary end points at 26 weeks were 1) noninferiority (95% CI upper bound <0.4% [<4.4 mmol/mol]) in HbA1c reduction with lixisenatide versus glulisine once daily, and either 2a) noninferiority in HbA1c reduction for lixisenatide versus glulisine thrice daily or 2b) superiority in body weight change for lixisenatide versus glulisine thrice daily. Fasting and postprandial plasma glucose, composite efficacy/safety end points, and adverse events were also assessed. RESULTS: Baseline characteristics were similar between arms (n = 298, diabetes and basal insulin duration of 12.2 and 3.2 years, respectively; BMI 32.2 kg/m(2)). HbA1c improved from 8.5% to 7.9% (69 to 63 mmol/mol) with glargine optimization and further to 7.2%, 7.2%, and 7.0% (55, 55, and 53 mmol/mol) with lixisenatide and glulisine once daily and thrice daily, respectively; all coprimary end points were met. Symptomatic hypoglycemia and body weight were lower in lixisenatide versus glulisine patients. More gastrointestinal events occurred with lixisenatide. CONCLUSIONS: Short-acting glucagon-like peptide-1 receptor agonists as add-on to basal insulin may become a preferred treatment intensification option, attaining meaningful glycemic targets with fewer hypoglycemic events without weight gain versus basal-plus or basal-bolus in uncontrolled basal insulin-treated type 2 diabetes.
RCT Entities:
OBJECTIVE: To provide evidence-based options on how to intensify basal insulin, we explored head-to-head prandial interventions in overweight patients with type 2 diabetes inadequately controlled on basal insulinglargine with or without 1-3 oral antidiabetic agents (OADs). RESEARCH DESIGN AND METHODS: Patients were randomized to lixisenatide once daily or insulinglulisine given once or thrice daily, added to glargine, with or without metformin, if HbA1c remained ≥7 to ≤9% (≥53 to ≤75 mmol/mol) after 12 weeks of glargine optimization with OADs other than metformin stopped at the start of optimization. Coprimary end points at 26 weeks were 1) noninferiority (95% CI upper bound <0.4% [<4.4 mmol/mol]) in HbA1c reduction with lixisenatide versus glulisine once daily, and either 2a) noninferiority in HbA1c reduction for lixisenatide versus glulisine thrice daily or 2b) superiority in body weight change for lixisenatide versus glulisine thrice daily. Fasting and postprandial plasma glucose, composite efficacy/safety end points, and adverse events were also assessed. RESULTS: Baseline characteristics were similar between arms (n = 298, diabetes and basal insulin duration of 12.2 and 3.2 years, respectively; BMI 32.2 kg/m(2)). HbA1c improved from 8.5% to 7.9% (69 to 63 mmol/mol) with glargine optimization and further to 7.2%, 7.2%, and 7.0% (55, 55, and 53 mmol/mol) with lixisenatide and glulisine once daily and thrice daily, respectively; all coprimary end points were met. Symptomatic hypoglycemia and body weight were lower in lixisenatide versus glulisinepatients. More gastrointestinal events occurred with lixisenatide. CONCLUSIONS: Short-acting glucagon-like peptide-1 receptor agonists as add-on to basal insulin may become a preferred treatment intensification option, attaining meaningful glycemic targets with fewer hypoglycemic events without weight gain versus basal-plus or basal-bolus in uncontrolled basal insulin-treated type 2 diabetes.
Authors: Minzhi Yu; Mason M Benjamin; Santhanakrishnan Srinivasan; Emily E Morin; Ekaterina I Shishatskaya; Steven P Schwendeman; Anna Schwendeman Journal: Adv Drug Deliv Rev Date: 2018-07-21 Impact factor: 15.470