Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Lixisenatide and Insulin Glargine, Versus Insulin Glargine in Type 2 Diabetes Inadequately Controlled on Metformin Monotherapy: The LixiLan Proof-of-Concept Randomized Trial.
- 2016
Available online from MWHC library: 1995 - present, Available in print through MWHC library: 1999 - 2006
CONCLUSIONS: LixiLan achieved statistically significant reductions to near-normal HbA1c levels with weight loss and no increased hypoglycemic risk, compared with insulin glargine alone, and a low incidence of gastrointestinal adverse events in type 2 diabetes inadequately controlled on metformin. Copyright � 2016 by the American Diabetes Association. OBJECTIVE: This study assessed the efficacy and safety of LixiLan, a fixed-ratio, titratable, combination of 2 units insulin glargine (Gla-100) and 1 mug lixisenatide administered once daily via a single pen, versus Gla-100 in insulin-naive type 2 diabetes on metformin. RESEARCH DESIGN AND METHODS: Participants were randomized to once-daily LixiLan (n = 161) or Gla-100 (n = 162) for 24 weeks, while continuing metformin. LixiLan and Gla-100 were started at 10 units/5 mug and 10 units, respectively, and titrated based on the Gla-100 requirement according to fasting plasma glucose levels. The primary objective was to test noninferiority (upper bound of the 95% CI <0.4%) of LixiLan in reducing HbA1c; if met, statistical superiority was tested. Secondary objectives included body weight changes, hypoglycemia, and safety. RESULTS: Baseline characteristics (mean age 57 years, diabetes duration 6-7 years, BMI 32 kg/m(2)) were similar between groups. At week 24, mean HbA1c was reduced from 8.0% (64 mmol/mol) at baseline to 6.3% (45 mmol/mol) and 6.5% (48 mmol/mol) with LixiLan and Gla-100, respectively, establishing statistical noninferiority and superiority of LixiLan (least-squared mean [95% CI] difference: -0.17% [-0.31, -0.04] ; P = 0.01). HbA1c <7.0% (<53 mmol/mol) was achieved in 84% and 78% of participants (nonsignificant), respectively. LixiLan improved 2-h postmeal plasma glucose versus Gla-100 (least-squared mean difference: -3.17 mmol/L [-57 mg/dL]; P < 0.0001). Body weight was reduced with LixiLan (-1 kg) and increased with Gla-100 (+0.5 kg; P < 0.0001), with no increase in hypoglycemic events (~25% in each group). The incidence of nausea (7.5%) and vomiting (2.5%) was low with LixiLan.
English
0149-5992
*Diabetes Mellitus, Type 2/dt [Drug Therapy] *Hypoglycemic Agents/tu [Therapeutic Use] *Insulin Glargine/tu [Therapeutic Use] *Metformin/tu [Therapeutic Use] *Peptides/tu [Therapeutic Use] Aged Blood Glucose/me [Metabolism] Body Weight Diabetes Mellitus, Type 2/me [Metabolism] Drug Combinations Drug Therapy, Combination Female Hemoglobin A, Glycosylated/me [Metabolism] Humans Hypoglycemia/ci [Chemically Induced] Male Middle Aged Postprandial Period Risk Safety