EFFICACY AND TOLERABILITY OF DIPEPTIDYL PEPTIDASE-4 INHIBITORS IN PATIENTS WITH DIABETES MELLITUS AND RENAL IMPAIRMENT: A SYSTEMATIC REVIEW AND META-ANALYSIS.

Jonas Auditorium

Objective. Evaluate efficacy and tolerability of DPP-4 inhibitors (DPP-4I) in patients with type 2 diabetes mellitus (T2DM) and chronic renal failure (CRF) using a systematic review and meta-analysis of available literature. Background. CRF is commonly found in patients with T2DM and the list of antidiabetic medications that can be used in this population is limited. Methods. Eight published randomized, clinical trials were identified from multiple databases. Qualitative assessment and quantitative analyses were performed. Results. Studies of DPP-4I included sitagliptin, saxagliptin, linagliptin and vildagliptin with 995 patients analyzed (average age 65 years, 56.4% males, 56.5% Caucasians, baseline A1c 7.9%). When compared with placebo, DPP-4I caused a reduction in A1c at 12 (-0.51%) and 52 (-0.72%) weeks, respectively, p < 0.00001, but reduction was not significantly different compared with glipizide. Subgroup analyses by severity of renal impairment showed DPP-4I caused a significant reduction in A1c with moderate (0.79) and severe (-0.62) renal impairment (p < 0.02). When compared with glipizide, DPP-4I were associated with weight loss at 12 and 54 weeks by 0.54Kg and 1.51Kg, respectively (p < 0.01). DPP-4I were associated with a numerical increase in rate of hypoglycemic events versus placebo (20.4% versus 16.4%, p=NS) but not when compared with glipizide (6.2% versus 15.5%, p=0.0009). There were no differences between DPP-4I and comparator for any adverse events (AE) (73.7% versus 75.1%), serious AE (19.1% versus 18.9%), any drugrelated AE (19.8% versus 21.1%) and withdrawals due to AE (7.6% versus 8.1%), respectively. Conclusion. Metaanalysis suggests that DPP-4I are effective and well-tolerated in patients with T2DM with CRF. Grants. N/A