Addition of Liraglutide to Insulin in Patients With Type 1 Diabetes: A Randomized Placebo-Controlled Clinical Trial of 12 Weeks

Diabetes Care. 2016 Jun;39(6):1027-35. doi: 10.2337/dc15-1136. Epub 2016 Apr 5.

Abstract

Objective: To investigate whether addition of three different doses of liraglutide to insulin in patients with type 1 diabetes (T1D) results in significant reduction in glycemia, body weight, and insulin dose.

Research design and methods: We randomized 72 patients (placebo = 18, liraglutide = 54) with T1D to receive placebo and 0.6, 1.2, and 1.8 mg liraglutide daily for 12 weeks.

Results: In the 1.2-mg and 1.8-mg groups, the mean weekly reduction in average blood glucose was -0.55 ± 0.11 mmol/L (10 ± 2 mg/dL) and -0.55 ± 0.05 mmol/L (10 ± 1 mg/dL), respectively (P < 0.0001), while it remained unchanged in the 0.6-mg and placebo groups. In the 1.2-mg group, HbA1c fell significantly (-0.78 ± 15%, -8.5 ± 1.6 mmol/mol, P < 0.01), while it did not in the 1.8-mg group (-0.42 ± 0.15%, -4.6 ± 1.6 mmol/mol, P = 0.39) and 0.6-mg group (-0.26 ± 0.17%, -2.8 ± 1.9 mmol/mol, P = 0.81) vs. the placebo group (-0.3 ± 0.15%, -3.3 ± 1.6 mmol/mol). Glycemic variability was reduced by 5 ± 1% (P < 0.01) in the 1.2-mg group only. Total daily insulin dose fell significantly only in the 1.2-mg and 1.8-mg groups (P < 0.05). There was a 5 ± 1 kg weight loss in the two higher-dose groups (P < 0.05) and by 2.7 ± 0.6 kg (P < 0.01) in the 0.6-mg group vs. none in the placebo group. In the 1.2- and 1.8-mg groups, postprandial plasma glucagon concentration fell by 72 ± 12% and 47 ± 12%, respectively (P < 0.05). Liraglutide led to higher gastrointestinal adverse events (P < 0.05) and ≤1% increases (not significant) in percent time spent in hypoglycemia (<55 mg/dL, 3.05 mmol/L).

Conclusions: Addition of 1.2 mg and 1.8 mg liraglutide to insulin over a 12-week period in overweight and obese patients with T1D results in modest reductions of weekly mean glucose levels with significant weight loss, small insulin dose reductions, and frequent gastrointestinal side effects. These findings do not justify the use of liraglutide in all patients with T1D.

Trial registration: ClinicalTrials.gov NCT01722266.

Publication types

  • Clinical Trial, Phase IV
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Body Weight
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / metabolism
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glucagon / metabolism
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Liraglutide / therapeutic use*
  • Male
  • Middle Aged
  • Obesity / complications
  • Overweight / complications
  • Postprandial Period
  • Time Factors
  • Treatment Outcome

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Liraglutide
  • Glucagon

Associated data

  • ClinicalTrials.gov/NCT01722266