Efficacy and Safety of iGlarLixi, Fixed-Ratio Combination of Insulin Glargine and Lixisenatide, Compared with Basal-Bolus Regimen in Patients with Type 2 Diabetes: Propensity Score Matched Analysis

Abstract

Introduction: Basal-bolus (BB) regimens are generally used to intensify basal insulin therapy in patients with type 2 diabetes (T2D) not meeting glycemic targets. However, drawbacks include multiple injection burden and risk of weight gain and hypoglycemia. A once-daily titratable fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide (iGlarLixi) may provide a simple, well-tolerated, and efficacious alternative. We compared these treatments in a post hoc propensity score matched analysis using randomized trial data.

Methods: From the LixiLan-L study, 195 patients who had been randomized to iGlarLixi were matched for age, sex, race, T2D duration, baseline body mass index, glycated hemoglobin (HbA1c), fasting plasma glucose, insulin dose, and metformin use to 195 patients who had been randomized to a BB regimen in the GetGoal Duo-2 trial.

Results: At study end, estimated treatment differences for reduction in HbA1c and weight change, and ratio of hypoglycemia events per patient-year (BB vs iGlarLixi) were - 0.28% (standard error 0.08, P = 0.0002), - 1.32 kg (standard error 0.30, P < 0.0001), and 2.85 (P < 0.0001), respectively, all favoring iGlarLixi over BB. Also, proportions of patients reaching individual and composite goals (HbA1c < 7% [< 53 mmol/mol], no weight gain, and no hypoglycemia) were higher in the iGlarLixi compared with the BB treatment group. Gastrointestinal side effects were more common with iGlarLixi.

Conclusions: In patients with T2D inadequately controlled on basal insulin, iGlarLixi offers an effective alternative to BB regimen for reducing HbA1c, without increased risk of hypoglycemia and weight gain.

Trial registration: ClinicalTrials.gov: NCT02058160 (LixiLan-L trial); NCT01768559 (GetGoal Duo-2 trial). Plain language summary available for this article.

Keywords: Hypoglycemia; Insulin therapy; Type 2 diabetes; Weight control; iGlarLixi.

Figures

Fig. 1

a HbA1c change from baseline and b weight change from baseline. Data labels represent mean HbA1c (%) or body weight (kg) at the corresponding time point. The changes from baseline in HbA1c and weight were analyzed using an MMRM with treatment groups and randomization strata (HbA1c [< 8.0%, ≥ 8.0% (< 64, ≥ 64 mmol/mol)] at screening and metformin use) as fixed effects, and visit (week 12 and week 24/26), baseline by visit interaction, and treatment by visit interaction as covariates. CI confidence interval, HbA1c glycated hemoglobin, iGlarLixi fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide, LS least squares, MMRM mixed-effects model with repeated measures, SE standard error

Fig. 2

Hypoglycemia events per patient-year. Hypoglycemia was defined as documented symptomatic hypoglycemia (plasma glucose concentration P values were estimated from Poisson regression with treatment as a fixed factor and log value of patient-years of exposure as an offset variable. iGlarLixi fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide

Fig. 3

Proportions of patients reaching a individual and b composite endpoints. Hypoglycemia was defined as documented symptomatic hypoglycemia (plasma glucose concentration < 54 mg/dL [< 3 mmol/L]). *P < 0.01 from Cochran–Mantel–Haenszel test for the weighted difference between treatment groups in all categories (randomization strata of HbA1c [< 8.0%, ≥ 8.0% (< 64, ≥ 64 mmol/mol)] and metformin use). CI confidence interval, HbA1c glycated hemoglobin, iGlarLixi fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide