Long-term efficacy and safety comparison of liraglutide, glimepiride and placebo, all in combination with metformin in type 2 diabetes: 2-year results from the LEAD-2 study

Research output: Contribution to journalArticle


Aims To investigate efficacy and safety of dual therapy with liraglutide and metformin in comparison to glimepiride and metformin, and metformin monotherapy over 2?years in patients with type 2 diabetes. Methods In the 26-week the Liraglutide Effect and Action in Diabetes (LEAD)-2 core trial, patients (n?=?1091) were randomized (2?:?2?:?2?:?1:?2) to liraglutide (0.6, 1.2 or 1.8?mg once-daily), placebo or glimepiride; all with metformin. Patients were enrolled if they were 1880?years old with HbA1c 7.011.0% (previous monotherapy =3?months), or 7.010.0% (previous combination therapy =3?months), and body mass index =40?kg/m2. Patients completing the 26-week double-blinded phase could enter an 18-month open-label extension. Results HbA1c decreased significantly with liraglutide (0.4% with 0.6?mg, 0.6% with 1.2 and 1.8?mg) versus 0.3% increase with metformin monotherapy (p?<?0.0001). HbA1c decrease with liraglutide was non-inferior versus 0.5% decrease with glimepiride. Liraglutide groups experienced significant weight loss (2.1, 3.0 and 2.9?kg with 0.6, 1.2 and 1.8?mg, respectively) compared to weight gain (0.7?kg) with glimepiride (p?<?0.0001). Weight loss with liraglutide 1.2 and 1.8?mg was significantly greater than with metformin monotherapy (1.8?kg; p?=?0.0185 and p?=?0.0378 for 1.2 and 1.8?mg, respectively). The occurrence of minor hypoglycaemia was <5.0% in all liraglutide groups, significantly less than with glimepiride (24.0%; p?<?0.0001). Liraglutide was well tolerated overall: gastrointestinal events were more common than with glimepiride or metformin monotherapy, but occurrence decreased with time. Conclusions Liraglutide provided sustained glycaemic control over 2?years comparable to that provided by glimepiride. Liraglutide was well tolerated, and was associated with weight loss and a low rate of hypoglycaemia.


  • M. Nauck
  • Anders Frid
  • K. Hermansen
  • A. B. Thomsen
  • M. During
  • N. Shah
  • T. Tankova
  • I. Mitha
  • D. R. Matthews
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes


  • GLP-1 analogue, type 2 diabetes
Original languageEnglish
Pages (from-to)204-212
JournalDiabetes, Obesity and Metabolism
Issue number3
Publication statusPublished - 2013
Publication categoryResearch

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Endocrinology (013241500), Pediatrics/Urology/Gynecology/Endocrinology (013240400)