Propensity-score-matched comparative analyses of simultaneously administered fixed-ratio insulin glargine 100 U and lixisenatide (iGlarLixi) vs sequential administration of insulin glargine and lixisenatide in uncontrolled type 2 diabetes

Diabetes Obes Metab. 2018 Dec;20(12):2821-2829. doi: 10.1111/dom.13462. Epub 2018 Aug 13.


Aim: To conduct two exploratory analyses to compare indirectly the efficacy and safety of simultaneous administration of insulin glargine 100 U (iGlar) and the glucagon-like peptide-1 receptor agonist (GLP-1RA) lixisenatide (Lixi) as a single-pen, titratable, fixed-ratio combination (iGlarLixi [LixiLan trials]) vs sequential administration of iGlar + Lixi (GetGoal Duo trials) in people with type 2 diabetes (T2D).

Materials and methods: Propensity-score matching based on baseline covariates was used to compare simultaneous iGlarLixi vs sequential combination of iGlar + Lixi with the addition of Lixi in patients who did not reach the glycated haemoglobin (HbA1c) goal of <53 mmol/mol (<7%) after short-term use of iGlar alone (LixiLan-O vs GetGoal Duo-1 comparison) and vs sequential addition of Lixi in uncontrolled patients after long-term use of iGlar alone (LixiLan-L vs GetGoal Duo-2 comparison).

Results: In both analyses, compared with sequential iGlar + Lixi, iGlarLixi led to significantly greater HbA1c reductions with associated weight loss and significantly more patients reaching target HbA1c <53 mmol/mol despite lower insulin doses. Symptomatic hypoglycaemia rates were similar, despite greater HbA1c reductions with iGlarLixi. Lower rates of gastrointestinal adverse events were observed with iGlarLixi, probably as a result of the more gradual titration of Lixi with iGlarLixi.

Conclusions: Indirect propensity-score-matched exploratory comparisons suggest that early treatment with a simultaneous, titratable, fixed-ratio combination of basal insulin and a GLP-1RA (iGlarLixi) may be more effective and possess better gastrointestinal tolerability than a sequential approach of adding a GLP-1RA in patients with uncontrolled T2D initiating or intensifying basal insulin therapy.

Trial registration: NCT00975286 NCT01768559 NCT02058160 NCT02058147.

Keywords: GLP-1; glycaemic control; insulin therapy; type 2 diabetes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Clinical Trials, Phase III as Topic
  • Comparative Effectiveness Research
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Administration Schedule
  • Drug Combinations
  • Drug Therapy, Combination
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Glycated Hemoglobin / drug effects
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / administration & dosage*
  • Insulin Glargine / administration & dosage*
  • Male
  • Middle Aged
  • Peptides / administration & dosage*
  • Propensity Score
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • Drug Combinations
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Peptides
  • hemoglobin A1c protein, human
  • Insulin Glargine
  • lixisenatide

Associated data