Efficacy & safety of switching from the DPP-4 inhibitor sitagliptin to the human GLP-1 analog liraglutide after 52 wks in metformin-treated patients

Pratley RE, Nauck MA, Bailey T, et al. 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. Diabetes Care. 2012;35(10):1986-1993.  

Background
In 2011, Pratley and colleagues reported 52-week data from a trial that explored treatment with the DPP-4 inhibitor, sitagliptin, and the GLP-1 receptor agonist, liraglutide, among subjects with type 2 diabetes and A1C 7.5%–10%.1 Participants had been receiving metformin ≥1,500 mg/day for ≥3 months; they continued metformin treatment and were randomized to sitagliptin 100 mg/day, or liraglutide 1.2 mg/day or 1.8 mg/day. The primary composite endpoint was A1C <7.0% with no weight gain or hypoglycemia. Other outcomes assessed included change in A1C, fasting plasma glucose (FPG), and weight.*

Results at 52 weeks showed greater reductions in A1C, FPG, and weight* with the 1.2-mg and 1.8-mg doses of liraglutide vs sitagliptin. Although liraglutide was superior to sitagliptin over 52 weeks, would this benefit continue over an extended treatment period? And, would outcomes improve for patients who were initially treated with sitagliptin if they were switched to liraglutide therapy?

Design
In a 26-week extension of the 2011 trial, sitagliptin-treated patients were randomized to liraglutide 1.2 mg/day (n=59) or 1.8 mg/day (n=63); subjects who initially received liraglutide retained their original treatment group assignment (n=124 in the 1.2-mg group; n=135 in the 1.8-mg group). The primary outcomes were safety and efficacy of switching therapies and of continuing liraglutide treatment; these efficacy and safety endpoints were identical to those used in the 52-week study. (Click here for slide.) 

Results at Week 78
Subjects switched from sitagliptin to liraglutide during 26-week extension

Reductions from Week 52 to Week 78 seen in

  • A1C: liraglutide 1.2 mg: 0.2% decrease (P=0.006); liraglutide 1.8 mg: 0.5% decrease (P=0.0001) (Click here for slide.)  
  • FPG: liraglutide 1.2 mg: 14.4 mg/dL decrease (P=0.004); liraglutide 1.8 mg: 25.2 mg/dL decrease (P<0.0001)
  • Weight:* liraglutide 1.2 mg: 1.6 kg decrease (P<0.0001); liraglutide 1.8 mg: 2.5 kg decrease (P<0.0001)

There was also a significant increase in the percentage of subjects reaching the primary composite endpoint of A1C <7.0% with no weight gain or hypoglycemia: liraglutide 1.2 mg: P=0.0018; liraglutide 1.8 mg: P=0.0192.

The majority of side effects experienced during the extension phase were mild or moderate, with the most frequent being GI issues. There was no major hypoglycemia, and minor hypoglycemia incidence was low. A slight increase in heart rate was seen in both liraglutide groups; the increase was only statistically significant for liraglutide 1.8 mg.

Subjects receiving liraglutide for full 78-week treatment period
Reductions from baseline in

  • A1C: liraglutide 1.2 mg: 0.9% decrease; liraglutide 1.8 mg: 1.3% decrease (Click here for slide.)  
  • FPG: liraglutide 1.2 mg: 23.4 mg/dL decrease; liraglutide 1.8 mg: 29.7 mg/dL decrease
  • Weight:* liraglutide 1.2 mg: 2.6 kg decrease; liraglutide 1.8 mg: 3.1 kg decrease

The composite endpoint was met in both treatment groups (% meeting endpoint): liraglutide 1.2 mg: 27.7%; liraglutide 1.8 mg: 43.7%.

Safety and tolerability profiles at Week 78 were similar to profiles seen during the first 52 weeks of the study: side effects were mild or moderate and most commonly related to GI issues, and 9-10% of subjects reported minor hypoglycemia. A slight increase in heart rate was seen at both 52 and 78 weeks; this increase was most evident among those who received the 1.8-mg dose of liraglutide.

*Sitagliptin and liraglutide are not FDA approved for weight reduction

1. Pratley RE, Nauck M, Bailey T, et al; for the 1860-LIRA-DPP-4 Study Group. One year of liraglutide treatment offers sustained and more effective glycaemic control and weight reduction compared with sitagliptin, both in combination with metformin, in patients with type 2 diabetes: a randomised, parallel-group, open-label trial. Int J Clin Pract. 2011;65(4):397-407.


 

December 2012  

This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.  

Related content: 

Clinical Insights® in Diabetes :: November 2012 

Slide: Liraglutide Vs Sitagliptin for Type 2 Diabetes: 1-Year Results Design  

Slide: Liraglutide Vs Sitagliptin for Type 2 Diabetes: 1-Year Results A1C Reduction  

Slide: Liraglutide Vs Sitagliptin for Type 2 Diabetes: 1-Year Results FPG Reduction  

Slide: Liraglutide Vs Sitagliptin for Type 2 Diabetes: 1-Year Results Additional Outcomes  

 

Last Modified: 11/15/2013