Effectiveness of IGlarLixi, a Fixed-Ratio Combination of Insulin Glargine 100 U/mL and Lixisenatide, in People with Type 2 Diabetes

Abstract

Introduction The latest Position Statement of the American Diabetes Association/European Association for the Study of Diabetes proposes the use of a fixed-ratio combination (FRC) of a long-acting basal insulin and a glucagon-like peptide-1 receptor agonist as part of treatment intensification. This study aimed to assess the effectiveness of the insulin glargine + lixisenatide (iGlarLixi) FRC on glycaemic control and hypoglycaemia in real-life settings. Methods This non-interventional, 26-week study included participants aged 18–80 years with suboptimally controlled type 2 diabetes (T2D) using oral antidiabetics (OADs) ± basal insulin therapy. The primary efficacy endpoint was the proportion of participants who achieved at least a 1% decrease in glycated haemoblobin (HbA1c) level from baseline to week 26. Results Of the 441 participants eligible for entry into the study, 353 were included in the efficacy analyses. These individuals were switched from OADs without (282 [79.9%]) or with (71 [20.1%]) insulin-based treatment. A reduction in HbA1c of at least 1.0% (primary endpoint) was achieved by 215 subjects (60.9%). All glycaemic variables (mean ± standard deviation) improved significantly during follow-up (HbA1c, from 8.9 ± 1.31 to 7.4 ± 0.97%; fasting blood glucose, from 9.0 ± 2.18 to 6.9 ± 1.23 mmol/L; postprandial blood glucose, from 11.3 ± 2.33 to 8.5 ± 1.46 mmol/L; p < 0.001 for all). Body weight also decreased during follow-up, from 90.5 ± 18.03 to 88.2 ± 17.75 kg ( p < 0.001). Overall, 41 participants (9.3% of the safety population) self-reported 101 non-severe hypoglycaemic episodes (incidence rate 0.498 events/person-year). There were no severe hypoglycaemic episodes reported. Gastrointestinal adverse events were reported by five participants (1.1% of the safety population). The vast majority (96.6%) of the study population continued iGlarLixi treatment after the final visit. Conclusion The results of this non-interventional study confirmed the efficacy results of the randomized controlled trial programme of the iGlarLixi FRC in a real-life setting. iGlarLixi significantly improved glycaemic control in association with a low frequency of hypoglycaemia and gastrointestinal adverse events in a heterogeneous population of participants with T2D suboptimally controlled with OADs ± basal insulin.

Effectiveness and Safety of iGlarLixi (Insulin Glargine 100 U/mL Plus Lixisenatide) in Type 2 Diabetes According to the Timing of Daily Administration: Data from the REALI Pooled Analysis

“…A comparable percentage of time over 24 h was spent with blood glucose levels between 70 and 180 mg/dL when iGlar-Lixi was administered pre-breakfast or pre-evening (73% versus 71%, respectively) [25]. Despite our analysis' encouraging effectiveness findings, there was a lower percentage of study participants achieving HbA1c target of \ 7.0% (26.4%) when compared with the percentage of Corresponding to real-life clinical practice, no forced titration of iGlarLixi was followed in the two pooled studies [13,14]. Hence, less stringent titration may explain the lower percentage of participants reaching HbA1c targets in the present pooled analysis compared to the Lix-iLan RCTs.…”

“…The present analysis pooled patient-level data from two 24-week observational studies [13,14] including adults with T2DM inadequately controlled on OADs with or without basal insulin who initiated iGlarLixi upon the treating physician-investigator's decision. In both studies, iGlarLixi (Suliqua Ò , Sanofi, Paris, France) was self-administered subcutaneously once daily within 1 h prior to a meal (preferably the same meal every day) for 24 weeks, using one of the two SoloStar Ò pen injectors.…”

“…Both pooled studies [13,14] were conducted according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines, and were approved by the relevant institutional review boards/ethics committees. This pooled analysis was also performed in accordance with the Helsinki Declaration of 1964 and its later amendments.…”

“…Secondary effectiveness endpoints included HbA1c change from baseline to week 12, proportions of participants achieving HbA1c targets of \ 7.0% (\ 53 mmol/mol), \ 7.5% (\ 58.5 mmol/mol) and \ 8.0% (\ 63.9 mmol/mol) at week 24, and changes from baseline to weeks 12 and 24 in FPG and 2-h PPG. Two-hour PPG was however collected in only one of the two pooled studies [13]. Safety endpoints included the incidence of hypoglycaemic events (symptomatic and severe) and gastrointestinal adverse events (AEs).…”

“…However, in the product label of iGlarLixi, it is stated, without specifying the injection time, that iGlarLixi should be injected once a day within 1 h prior to a meal (or first meal as per US label) [11], preferably before the same meal every day, when the most convenient meal has been chosen [12]. By using pooled data from two real-world, prospective, observational studies [13,14], we sought to evaluate in routine clinical practice the effectiveness and safety of iGlarLixi in individuals with T2DM inadequately controlled on OADs with or without basal insulin, according to its time of administration (i.e. before breakfast, lunch, dinner, or in case the time of the prandial injection was changed during the study period).…”