Efficacy and safety of switching from the DPP-4 inhibitor sitagliptin to the human GLP-1 analog liraglutide after 52 weeks in metformin-treated patients with type 2 diabetes: a randomized, open-label trial

Abstract

Objective: To assess the efficacy and safety of switching from sitagliptin to liraglutide in metformin-treated adults with type 2 diabetes.

Research design and methods: In an open-label trial, participants randomized to receive either liraglutide (1.2 or 1.8 mg/day) or sitagliptin (100 mg/day), each added to metformin, continued treatment for 52 weeks. In a 26-week extension, sitagliptin-treated participants were randomly allocated to receive instead liraglutide at either 1.2 or 1.8 mg/day, while participants originally randomized to receive liraglutide continued unchanged.

Results: Although 52 weeks of sitagliptin changed glycosylated hemoglobin (HbA(1c)) by -0.9% from baseline, additional decreases occurred after switching to liraglutide (1.2 mg/day, -0.2%, P = 0.006; 1.8 mg/day, -0.5%, P = 0.0001). Conversion to liraglutide was associated with reductions in fasting plasma glucose (FPG) (1.2 mg/day, -0.8 mmol/L, P = 0.0004; 1.8 mg/day, -1.4 mmol/L, P < 0.0001) and body weight (1.2 mg/day, -1.6 kg; 1.8 mg/day, -2.5 kg; both P < 0.0001) and with an increased proportion of patients reaching HbA(1c) <7% (from ∼30% to ∼50%). Overall treatment satisfaction, assessed by the Diabetes Treatment Satisfaction Questionnaire, improved after switching to liraglutide (pooled 1.2 and 1.8 mg/day, 1.3; P = 0.0189). After switching, mostly transient nausea occurred in 21% of participants, and minor hypoglycemia remained low (3-4% of participants). Continuing liraglutide treatment at 1.2 mg/day and 1.8 mg/day for 78 weeks reduced HbA(1c) (baseline 8.3 and 8.4%, respectively) by -0.9 and -1.3%, respectively; FPG by -1.3 and -1.7 mmol/L, respectively; and weight by -2.6 and -3.1 kg, respectively, with 9-10% of participants reporting minor hypoglycemia.

Conclusions: Glycemic control, weight, and treatment satisfaction improved after switching from sitagliptin to liraglutide, albeit with a transient increase in gastrointestinal reactions.

Figure 1

Trial flow diagram. Data are n (%) participants unless otherwise noted. *Participants were withdrawn if they fulfilled withdrawal criteria, decided against participation, or did not attend any postrandomization visits. Participant disposition during the study extension is shown in bold. †Numbers and percentages of participants are from the extension analysis set.

Figure 2

Selected efficacy and safety parameters. Mean HbA_1c (A), FPG (B), and change in body weight (C) during 78 weeks for participants originally randomly allocated to receive liraglutide and participants switched to liraglutide after 52 weeks (Wk). D: Proportions of switch group participants (%) reaching target HbA_1c <7.0% or ≤6.5% at weeks 52 and 78. E: Proportions of switch group participants reaching composite end point of HbA_1c <7.0%, with no weight gain and no confirmed major or minor hypoglycemia, at weeks 52 and 78. F: Changes in the DTSQ scores from week 52 to week 78 (pooled liraglutide switch groups). *P < 0.05, **P < 0.01, ***P < 0.0001. G: Nausea incidence during weeks 0–78. For participants switched to liraglutide at week 52 in panels A, B, and C, the dashed lines represent the main trial period, whereas solid lines represent the extension (weeks 53–78). For D and E, estimates are from a logistic regression model, with treatment and country as fixed effects and baseline HbA_1c and body weight (for composite) as covariates. Error bars are 1.96 × SE, corresponding to the 95% CI. Filled blue squares indicate liraglutide 1.2 mg/day, filled maroon circles indicate liraglutide 1.8 mg/day, filled red diamonds indicate sitagliptin to liraglutide 1.2 mg/day, and filled pink triangles indicate sitagliptin to liraglutide 1.8 mg/day.