Effectiveness, Safety, and Appropriateness in the Use of the Fixed-Ratio Combination of Insulin Glargine and Lixisenatide in Type 2 Diabetes: The ENSURE Retrospective Real-World Study

Introduction Pivotal trials documented glycemic benefits of fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide (iGlarLixi), with no weight gain and low hypoglycemia risk in type 2 diabetes (T2D). This study aimed at assessing effectiveness and patterns of use of iGlarLixi in a real-world setting. Methods This was a retrospective, multicenter, study, based on electronic medical records. All patients initiating iGlarLixi from May 2018 to July 2020 were considered. Results Overall, 25 centers provided data on 675 patients initiating iGlarLixi with the following characteristics: age 66.4 +/- 10.1 years, 54.2% men, T2D duration 15.5 +/- 11.5 years, HbA1c 8.6 +/- 1.4%, body mass index (BMI) 30.8 +/- 5.3 kg/m(2), 45.1% already treated with basal insulin, and 21.9% with basal bolus (+/- oral hypoglycemic agents). Metformin and sodium-glucose cotransporter-2 inhibitors were used in 76.0% and 0.9% of patients, respectively. Combinations of iGlarLixi with other glucose-lowering drugs such as sulfonylureas or short-acting insulin were found in 32.4% of patients. Effectiveness of iGlarLixi (N = 184) showed that HbA1c declined by 0.77% [95% confidence interval (CI) -1.00, -0.54] after 6 months. In combination with metformin and/or SGLT-2i (N = 117), HbA1c declined by -0.92% (95% CI -1.22, -0.62) and weight significantly decreased by 1.21 kg. iGlarLixi dose was suboptimally titrated. Safety data (N = 171) showed incidence rates of blood glucose <= 70 and < 54 mg/mL of 0.26 and 0.05 events per person-month during 6 months, respectively, with a risk reduction of about 75% with respect the 6 months before iGlarLixi initiation. No severe hypoglycemia was reported. Conclusion In adults with T2D, effectiveness and safety of iGlarLixi were documented in a real-world setting; appropriateness of use and adequate titration should be urgently improved so that clinical practice outcomes become more comparable to clinical trials results. Further real-world studies on the effect of iGlarLixi therapy are warranted.