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

Aims: To investigate efficacy and safety of dual therapy with liraglutide and metformin in comparison to glimepiride and metformin, and metformin monotherapy over 2years 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 1.8mg once-daily), placebo or glimepiride; all with metformin. Patients were enrolled if they were 18-80years old with HbA1c 7.0-11.0% (previous monotherapy ≥3months), or 7.0-10.0% (previous combination therapy ≥3months), and body mass index ≤40kg/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 0.6mg, 0.6% with 1.2 and 1.8mg) 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 2.9kg with 0.6, 1.2 and 1.8mg, respectively) compared to weight gain (0.7kg) with glimepiride (p<0.0001). Weight loss with liraglutide 1.2 and 1.8mg was significantly greater than with metformin monotherapy (1.8kg; p=0.0185 and p=0.0378 for 1.2 and 1.8mg, 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. © 2012 Blackwell Publishing Ltd.