Contribution of liraglutide in the fixed-ratio combination of insulin degludec and liraglutide (IDegLira)

Diabetes Care. 2014 Nov;37(11):2926-33. doi: 10.2337/dc14-0785. Epub 2014 Aug 11.

Abstract

Objective: Insulin degludec/liraglutide (IDegLira) is a novel combination of insulin degludec (IDeg) and liraglutide. This trial investigated the contribution of the liraglutide component of IDegLira versus IDeg alone on efficacy and safety in patients with type 2 diabetes.

Research design and methods: In a 26-week, double-blind trial, patients with type 2 diabetes (A1C 7.5-10.0% [58-86 mmol/mol]) on basal insulin (20-40 units) and metformin with or without sulfonylurea/glinides were randomized (1:1) to once-daily IDegLira + metformin or IDeg + metformin with titration aiming for fasting plasma glucose between 4 and 5 mmol/L. Maximum allowed doses were 50 dose steps (equal to 50 units IDeg plus 1.8 mg liraglutide) and 50 units for IDeg. The primary end point was change in A1C from baseline.

Results: A total of 413 patients were randomized (mean A1C 8.8% [73 mmol/mol]; BMI 33.7 kg/m2). IDeg dose, alone or as part of IDegLira, was equivalent (45 units). A1C decreased by 1.9% (21 mmol/mol) with IDegLira and by 0.9% (10 mmol/mol) with IDeg (estimated treatment difference -1.1% [95% CI -1.3, -0.8], -12 mmol/mol [95% CI -14, -9; P < 0.0001). Mean weight reduction with IDegLira was 2.7 kg vs. no weight change with IDeg, P < 0.0001. Hypoglycemia incidence was comparable (24% for IDegLira vs. 25% for IDeg). Overall adverse events were similar, and incidence of nausea was low in both groups (IDegLira 6.5% vs. IDeg 3.5%).

Conclusions: IDegLira achieved glycemic control superior to that of IDeg at equivalent insulin doses without higher risk of hypoglycemia and with the benefit of weight loss. These findings establish the efficacy and safety of IDegLira and the distinct contribution of the liraglutide component.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Drug Combinations
  • Drug Therapy, Combination
  • Female
  • Glucagon-Like Peptide 1 / administration & dosage
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptide 1 / therapeutic use
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemia / epidemiology
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use*
  • Insulin, Long-Acting / administration & dosage
  • Insulin, Long-Acting / therapeutic use*
  • Liraglutide
  • Male
  • Metformin / administration & dosage
  • Metformin / therapeutic use
  • Middle Aged
  • Sulfonylurea Compounds / administration & dosage
  • Sulfonylurea Compounds / therapeutic use
  • Treatment Outcome
  • Weight Loss / drug effects

Substances

  • Blood Glucose
  • Drug Combinations
  • Hypoglycemic Agents
  • Insulin, Long-Acting
  • Sulfonylurea Compounds
  • insulin degludec
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Metformin