Long-term treatment with the dipeptidyl peptidase-4 inhibitor saxagliptin in patients with type 2 diabetes mellitus and renal impairment

Nowicki M, Rychlik I, Haller H, et al.
Int J Clin Pract. 2011;65(12):1230-1239. 

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Nowicki and colleagues examined the effects of the dipeptidyl peptidase-4 (DPP-4) inhibitor, saxagliptin, among patients with inadequately controlled type 2 diabetes and renal impairment in a 52-week study. 

Subjects were enrolled in an initial 12-week, randomized, parallel-group, double-blind study that continued to a 40-week controlled extension study. Subjects were all Caucasian; mean age was 67 years. All subjects were stratified based on degree of renal impairment at baseline (per creatinine clearance [CrCl]): moderate (CrCl ≥30 and <50 ml/min), severe (CrCl <30 ml/min and not receiving dialysis), or end-stage renal disease (ESRD; on hemodialysis at baseline). Study randomization was in a 1:1 ratio in balanced blocks based on renal impairment category designation. Subjects received double-blind treatment with saxagliptin 2.5 mg or placebo. Subjects could continue other antidiabetic drugs if taken at baseline; addition of new drugs was permitted with the exception of thiazolidinediones, glucagon-like peptide-1 agonists, metformin, or other DPP-4 inhibitors.  

The primary endpoint was change in A1C from baseline to week 12. Secondary endpoints were efficacy at 52 weeks based on changes in A1C and fasting plasma glucose (FPG) from baseline and changes from baseline in doses and/or type of background antidiabetic therapy and insulin.  

Of 170 subjects randomized, 76% (n=129) completed the 12-week treatment period and 54% (n=92) completed the 52-week treatment period (n=42 treated with saxagliptin; n=50 treated with placebo). Baseline levels of A1C and FPG were higher among saxagliptin-treated subjects vs those who received placebo.  

Results at 52 weeks:  

  • Greater mean change in A1C from baseline observed in saxagliptin-treated subjects (-1.08% [95% CI, -1.37 to -0.80]) vs those receiving placebo (-0.36 [95% CI, -0.63 to -0.08]; between-group difference, -0.73% [95% CI, -1.11 to -0.34]; P<0.001)  
  • When examined based on stratified groups of renal impairment, A1C reductions were greater among saxagliptin-treated subjects with moderate or severe renal impairment compared with those treated with placebo; reductions were similar for subjects with ESRD in both treatment groups  
  • Majority of adverse events were mild or moderate; most frequent among subjects in the saxagliptin group were urinary tract infection, hypertension, dyspnoea, and anemia. Rates of hypoglycemic events were similar between the saxagliptin and placebo groups (132 events in 24 subjects [28%]) vs 90 events in 25 subjects [29%], respectively)  

 

Don’t miss these slides in our Slide Library: 

Saxagliptin for Treatment of Subjects with Type 2 Diabetes and Renal Impairment: Design 
Saxagliptin for Treatment of Subjects with Type 2 Diabetes and Renal Impairment: Change in A1C from Baseline to Week 52
Saxagliptin for Treatment of Subjects with Type 2 Diabetes and Renal Impairment: Additional Results 

 

 This overview was created under the auspices of KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional interest. 

 

Last Modified: 11/18/2013