Efficacy and safety of switching from the DPP-4 inhibitor sitagliptin to the human GLP-1 analog liraglutide after 52 weeks in metformin-treated patients with type 2 diabetes: a randomized, open-label trial

Diabetes Care. 2012 Oct;35(10):1986-93. doi: 10.2337/dc11-2113. Epub 2012 Jul 30.

Abstract

Objective: To assess the efficacy and safety of switching from sitagliptin to liraglutide in metformin-treated adults with type 2 diabetes.

Research design and methods: In an open-label trial, participants randomized to receive either liraglutide (1.2 or 1.8 mg/day) or sitagliptin (100 mg/day), each added to metformin, continued treatment for 52 weeks. In a 26-week extension, sitagliptin-treated participants were randomly allocated to receive instead liraglutide at either 1.2 or 1.8 mg/day, while participants originally randomized to receive liraglutide continued unchanged.

Results: Although 52 weeks of sitagliptin changed glycosylated hemoglobin (HbA(1c)) by -0.9% from baseline, additional decreases occurred after switching to liraglutide (1.2 mg/day, -0.2%, P = 0.006; 1.8 mg/day, -0.5%, P = 0.0001). Conversion to liraglutide was associated with reductions in fasting plasma glucose (FPG) (1.2 mg/day, -0.8 mmol/L, P = 0.0004; 1.8 mg/day, -1.4 mmol/L, P < 0.0001) and body weight (1.2 mg/day, -1.6 kg; 1.8 mg/day, -2.5 kg; both P < 0.0001) and with an increased proportion of patients reaching HbA(1c) <7% (from ∼30% to ∼50%). Overall treatment satisfaction, assessed by the Diabetes Treatment Satisfaction Questionnaire, improved after switching to liraglutide (pooled 1.2 and 1.8 mg/day, 1.3; P = 0.0189). After switching, mostly transient nausea occurred in 21% of participants, and minor hypoglycemia remained low (3-4% of participants). Continuing liraglutide treatment at 1.2 mg/day and 1.8 mg/day for 78 weeks reduced HbA(1c) (baseline 8.3 and 8.4%, respectively) by -0.9 and -1.3%, respectively; FPG by -1.3 and -1.7 mmol/L, respectively; and weight by -2.6 and -3.1 kg, respectively, with 9-10% of participants reporting minor hypoglycemia.

Conclusions: Glycemic control, weight, and treatment satisfaction improved after switching from sitagliptin to liraglutide, albeit with a transient increase in gastrointestinal reactions.

Publication types

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

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Glucagon-Like Peptide 1 / adverse effects
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptide 1 / therapeutic use
  • Glycated Hemoglobin / metabolism
  • Humans
  • Liraglutide
  • Metformin / administration & dosage
  • Nausea / chemically induced
  • Patient Satisfaction
  • Pyrazines / therapeutic use*
  • Sitagliptin Phosphate
  • Treatment Outcome
  • Triazoles / therapeutic use*

Substances

  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Pyrazines
  • Triazoles
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Metformin
  • Sitagliptin Phosphate