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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
Author(s) -
Nauck M.,
Frid A.,
Hermansen K.,
Thomsen A. B.,
During M.,
Shah N.,
Tankova T.,
Mitha I.,
Matthews D. R.
Publication year - 2013
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12012
Subject(s) - glimepiride , metformin , liraglutide , medicine , type 2 diabetes , placebo , weight loss , gastroenterology , combination therapy , diabetes mellitus , urology , endocrinology , obesity , alternative medicine , pathology
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 18–80 years old with HbA1c 7.0–11.0% (previous monotherapy ≥3 months), or 7.0–10.0% (previous combination therapy ≥3 months), and body mass index ≤40 kg/m 2 . 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.