Liraglutide, a once-daily human glucagon-like peptide 1 analogue, provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetes

Abstract

Aims: Most treatments for type 2 diabetes fail over time, necessitating combination therapy. We investigated the safety, tolerability and efficacy of liraglutide monotherapy compared with glimepiride monotherapy over 2 years.

Methods: Participants were randomized to receive once-daily liraglutide 1.2 mg, liraglutide 1.8 mg or glimepiride 8 mg. Participants completing the 1-year randomized, double-blind, double-dummy period could continue open-label treatment for an additional year. Safety data were evaluated for the full population exposed to treatment, and efficacy data were evaluated for the full intention-to-treat (ITT) and 2-year completer populations. Outcome measures included change in glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight and frequency of nausea and hypoglycaemia.

Results: For patients completing 2 years of therapy, HbA1c reductions were -0.6% with glimepiride versus -0.9% with liraglutide 1.2 mg (difference: -0.37, 95% CI: -0.71 to -0.02; p = 0.0376) and -1.1% with liraglutide 1.8 mg (difference: -0.55, 95% CI: -0.88 to -0.21; p = 0.0016). In the ITT population, HbA1c reductions were -0.3% with glimepiride versus -0.6% with liraglutide 1.2 mg (difference: -0.31, 95% CI: -0.54 to -0.08; p = 0.0076) and -0.9% with liraglutide 1.8 mg (difference: -0.60, 95% CI: -0.83 to -0.38; p < 0.0001). For both ITT and completer populations, liraglutide was more effective in reducing HbA1c, FPG and weight. Over 2 years, rates of minor hypoglycaemia [self-treated plasma glucose <3.1 mmol/l (<56 mg/dl)] were significantly lower with liraglutide 1.2 mg and 1.8 mg compared with glimepiride (p < 0.0001).

Conclusion: Liraglutide monotherapy for 2 years provides significant and sustained improvements in glycaemic control and body weight compared with glimepiride monotherapy, at a lower risk of hypoglycaemia.

Figure 1

Participant flow during the LEAD-3 trial. ITT, intention-to-treat.

Figure 2

HbA1c over time. (A) Two-year completer population, observed mean values, no imputation. (B) Intention-to-treat (ITT) population, observed mean values, no imputation. (C) ITT population, estimated least square (LS) mean values derived from an analysis of covariance (ancova) model with repeated measures. (D) Two-year completer population, participants previously treated with diet and exercise, observed mean values, no imputation. Error bars are ±2s.e. Panel C: ^*p < 0.0001 vs. glimepiride; ^**p < 0.05 vs. glimepiride.

Figure 3

Additional efficacy endpoints for 2-year completers. (A) Percentage of participants treated to HbA1c targets <7% (<53 mmol/mol) (left graph) and ≤6.5% (≤48 mmol/mol) (right graph) at 2 years. (B) Fasting plasma glucose (FPG) (mmol/l) over time. (C) Change in FPG (mmol/l) from baseline to week 104. (D) Body weight (kg) over time. (E) Change in body weight (kg) from baseline to week 104. Data in panel A are estimated percentages from a logistic regression model. Data in panels B and D are observed means. Data in panels C and E are least square (LS) means from an analysis of covariance (ancova) model. Error bars are ±2s.e. ETD = estimated treatment difference (liraglutide–glimepiride).