Efficacy and safety benefits of iGlarLixi versus insulin glargine 100 U/mL or lixisenatide in Asian Pacific people with suboptimally controlled type 2 diabetes on oral agents: The LixiLan-O-AP randomized controlled trial

Diabetes Obes Metab. 2022 Aug;24(8):1522-1533. doi: 10.1111/dom.14722. Epub 2022 May 12.

Abstract

Aims: To compare the efficacy and safety of iGlarLixi with insulin glargine 100 units/mL (iGlar) and lixisenatide (Lixi), in Asian Pacific people with suboptimally controlled type 2 diabetes (T2D) on metformin with or without a second oral antihyperglycaemic drug (OAD).

Materials and methods: LixiLan-O-AP (NCT03798054) was a 24-week multicentre study in adults (n = 878, mean age 56.0 years, mean body mass index 26.0 kg/m2 ) with glycated haemoglobin (HbA1c) levels ≥53 mmol/mol (7%) and ≤97 mmol/mol (11%) on OAD(s), randomized (2:2:1) to open-label once-daily iGlarLixi, iGlar or Lixi while on continued metformin ± sodium-glucose cotransporter-2 inhibitors. The primary efficacy endpoint was change in HbA1c.

Results: After 24 weeks, greater reductions in HbA1c from baseline (67 mmol/mol; 8.3%) were seen with iGlarLixi (-21 mmol/mol; -1.9%) compared with iGlar (-16 mmol/mol; -1.4%; P < 0.0001) and Lixi (-10 mmol/mol; -0.9%; P < 0.0001). Greater proportions of participants achieved HbA1c <53 mmol/mol (<7%) with iGlarLixi versus iGlar or Lixi (79%, 60% and 30%, respectively), overall and as composite endpoints including weight and hypoglycaemia. iGlarLixi improved 2-hour postprandial glucose versus iGlar and Lixi and mitigated the weight gain seen with iGlar (least squares mean difference -1.1 kg; P < 0.0001). Documented ≤3.9 mmol/L (≤70 mg/dL) hypoglycaemia was similar between iGlarLixi and iGlar (both 3.38 events per participant-year). The incidence rates of nausea and vomiting were lower with iGlarLixi (14% and 6%) than Lixi (21% and 11%).

Conclusions: iGlarLixi achieved significant HbA1c reductions, to near-normoglycaemic levels, compared with iGlar or Lixi, with no meaningful additional risk of hypoglycaemia and mitigated body weight gain versus iGlar, with fewer gastrointestinal adverse events versus Lixi. iGlarLixi with specifically adapted ratios may provide an efficacious and well-tolerated treatment option for Asian Pacific people with T2D.

Keywords: GLP-1 analogue; basal insulin; glycaemic control; hypoglycaemia; iGlarLixi; type 2 diabetes.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Blood Glucose
  • Diabetes Mellitus, Type 2* / chemically induced
  • Diabetes Mellitus, Type 2* / drug therapy
  • Drug Combinations
  • Glycated Hemoglobin
  • Humans
  • Hypoglycemia* / chemically induced
  • Hypoglycemia* / epidemiology
  • Hypoglycemia* / prevention & control
  • Hypoglycemic Agents / adverse effects
  • Insulin Glargine / adverse effects
  • Metformin* / adverse effects
  • Middle Aged
  • Peptides
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Weight Gain

Substances

  • Blood Glucose
  • Drug Combinations
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Peptides
  • Sodium-Glucose Transporter 2 Inhibitors
  • Insulin Glargine
  • lixisenatide
  • Metformin

Associated data

  • ClinicalTrials.gov/NCT03798054