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Randomized Comparison of Initiating the Fixed-Ratio Combination of iGlarLixi or Biosimilar Insulin Glargine Together With Gliclazide in Participants of South Asian Origin With Type 2 Diabetes: VARIATION 2 SA Trial

Published:February 11, 2022DOI:https://doi.org/10.1016/j.jcjd.2022.02.003

      Abstract

      Objectives

      The objective of this study was to compare initiation of a fixed-ratio combination of insulin glargine and lixisenatide (iGlarLixi) vs insulin glargine U100 (iGlar) along with gliclazide, exclusively in people of South Asian origin with type 2 diabetes (T2D).

      Methods

      The Variability of glucose Assessed in a Randomized trial comparing the Initiation of A Treatment approach with biosimilar basal Insulin analog Or a titratable iGlarLixi combinatioN in type 2 diabetes among South Asian participants (VARIATION 2 SA) trial (ClinicalTrials.gov identifier: NCT03819790) randomized insulin-naïve adults with T2D having glycated hemoglobin (A1C) 7.1% to 11% to initiate either iGlarLixi or iGlar + gliclazide. Insulin doses were titrated similarly to a prebreakfast glucose target of 4.0 to 5.5 mmol/L. Average time in range (TIR) on a masked continuous glucose monitor (CGM), A1C, fasting plasma glucose (FPG) and weight were assessed at the end of the 12-week treatment period.

      Results

      Mean baseline characteristics for the 104 randomized participants were similar between treatment groups, including the following: age, 59±11 years; diabetes duration, 13.7±7.3 years; and A1C, 8.5%±1.2%. Coprimary outcomes of average TIRs within 24- and 12-h (6 am to 6 pm) periods at the end of trial were 70.5%±16.8% and 72.9%±17.6% for iGlarLixi, whereas these TIRs were 65.6%±21.6% and 67.3%±20.7% for the iGlar + gliclazide regimen, respectively, with no significant differences between groups (p=0.35 for 24-h TIR and p=0.14 for 12-h TIR). No significant difference in secondary outcomes was observed between treatment groups. Self-reported hypoglycemic events throughout the trial period and CGM-reported hypoglycemia (<4 and <3 mmol/L) were similar between randomized treatments.

      Conclusions

      Initiation of iGlarLixi resulted in similar TIR, A1C, FPG, weight and hypoglycemia compared with the more affordable option of starting iGlar + gliclazide in adults of South Asian origin with T2D.

      Résumé

      Objectifs

      L’objectif visait à comparer l’instauration d’une combinaison à ratio fixe d’insuline glargine et de lixisénatide (iGlarLixi) à l’insuline glargine U100 (iGlar) et le gliclazide, exclusivement chez les personnes d’origine sud-asiatique atteintes du diabète de type 2 (DT2).

      Méthodes

      L’étude à répartition aléatoire VARIATION 2 SA (ClinicalTrials.gov identifiant : NCT03819790) portait sur des adultes DT2 insulino-naïfs qui avaient une hémoglobine glyquée (A1c) de 7,1 % à 11 % avant l’instauration de l’iGlarLixi ou de l’iGlar + gliclazide. La titration des doses d’insuline était similaire aux valeurs cibles de la glycémie avant le déjeuner de 4,0 à 5,5 mmol/L. Le temps moyen passé dans les limites de la cible glycémique (TIR, de l’anglais time in range) sur un lecteur de glycémie en continu (LGC) en mode masqué, l’A1c, la glycémie veineuse à jeun (GVJ) et le poids étaient évalués à la fin de la période de traitement de 12 semaines.

      Résultats

      Les caractéristiques initiales moyennes des 104 participants répartis de façon aléatoire étaient similaires entre les groupes de traitement, notamment l’âge de 59 ± 11 ans, la durée du diabète de 13,7 ± 7,3 ans et l’A1c de 8,5 % ± 1,2 %. Les cocritères d’évaluation principaux des TIR moyens sur des périodes de 24 h et de 12 h (de 6 h à 18 h) à la fin de l’étude étaient de 70,5 % ± 16,8 % et de 72,9 % ± 17,6 % pour l’iGlarLixi, tandis que ces TIR étaient respectivement de 65,6 % ± 21,6 % et de 67,3 % ± 20,7 % pour le traitement de l’iGlar + gliclazide. Toutefois, il n’y avait aucune différence significative entre les groupes (p = 0,35 pour le TIR de 24 h et p = 0,14 pour le TIR de 12 h). Aucune différence significative dans les critères secondaires n’a été observée entre les groupes de traitement. Les épisodes d’hypoglycémie auto-déclarés durant toute la période de l’étude et l’hypoglycémie relevée par le LGC (< 4 et < 3 mmol/L) étaient similaires entre les groupes de traitements.

      Conclusions

      L’instauration de l’iGlarLixi s’est traduite par un TIR, une A1c, une GVJ, un poids et une hypoglycémie similaires à l’option la plus abordable de l’iGlar + gliclazide chez les adultes d’origine sud-asiatique atteints du DT2.

      Keywords

      Mots clés

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