Efficacy and safety of liraglutide versus sitagliptin, both in combination with metformin, in Chinese patients with type 2 diabetes: a 26-week, open-label, randomized, active comparator clinical trial

Abstract

Aims: To compare the efficacy and safety of liraglutide versus sitagliptin as add-on to metformin after 26 weeks of treatment in Chinese patients with type 2 diabetes mellitus (T2DM).

Methods: This 26-week open-label, active comparator trial (NCT02008682) randomized patients (aged 18-80 years) with T2DM inadequately controlled with metformin [glycated haemoglobin (HbA1c) 7.0-10.0% (53-86 mmol/mol)] 1 : 1 to once-daily subcutaneously administered liraglutide 1.8 mg (n = 184) or once-daily oral sitagliptin 100 mg (n = 184), both as add-on to metformin. The primary endpoint was change in HbA1c from baseline to week 26.

Results: Liraglutide was superior to sitagliptin in reducing HbA1c from baseline [8.1% (65 mmol/mol)] to 26 weeks, as evidenced by estimated mean HbA1c change of -1.65% (-18.07 mmol/mol) versus -0.98% (-10.72 mmol/mol), respectively [estimated treatment difference for liraglutide vs sitagliptin of -0.67% (95% CI -0.86, -0.48) or -7.35 mmol/mol (95% CI -9.43; -5.26); p < 0.0001]. More patients receiving liraglutide (76.5%) than sitagliptin (52.6%) achieved the HbA1c target of <7.0% (53 mmol/mol) at week 26 [odds ratio 3.65 (95% CI 2.18, 6.12); p < 0.0001]. Reductions in fasting plasma glucose, 7-point self-measured plasma glucose and body weight were greater with liraglutide than with sitagliptin (p < 0.0001 for all). More patients experienced nausea (14.8% vs 0.5%), diarrhoea (8.2% vs 2.2%) and decreased appetite (10.9% vs 0.5%) with liraglutide than sitagliptin. Two hypoglycaemic episodes were confirmed for liraglutide and one for sitagliptin; none were severe or nocturnal.

Conclusions: Liraglutide provided better glycaemic control and greater body weight reduction than sitagliptin when administered as add-on to metformin. More patients had nausea, diarrhoea and decreased appetite with liraglutide versus sitagliptin.

Keywords: Chinese; liraglutide; sitagliptin; type 2 diabetes.

Figure 1

Patient disposition. *One patient withdrew before exposure. Discontinuation: patients stopped trial product but remained in the trial to collect end of trial safety and efficacy information. Withdrawn: patients stopped trial product and left the trial.

Figure 2

Efficacy endpoints from baseline to week 26. (A) HbA1c estimated means [±standard error of mean (s.e.m.)]. (B) Change in glycated haemoglobin (HbA1c). (C) Fasting plasma glucose estimated means (±s.e.m.). (D) Seven‐point self‐measured plasma glucose profiles. Dashed line: baseline; solid line: week 26. (E) Body weight estimated means (±s.e.m.). For (A), (C), (D) and (E): squares, liraglutide; triangles, sitagliptin.

Figure 3

Proportion of patients achieving treatment targets and composite endpoints after 26 weeks of treatment. (A) Glycated haemoglobin (HbA1c) <7.0% (53 mmol/mol) and ≤6.5% (48 mmol/mol) the composite endpoints. (B) Post hoc weight loss ≤5% and composite endpoints. CI, confidence interval; SBP, systolic blood pressure. Hypoglycaemia refers to confirmed hypoglycaemia. p values refer to odds ratios.