OBJECTIVES: Dipeptidyl peptidase-4 inhibitors (DPP4I) include sitagliptin, saxagliptin, vildagliptin and linagliptin.  Except for linagliptin, dosage adjustments based on renal function are recommended to avoid adverse events (e.g., hypoglycemia).  However, data on the effect of DPP4I on hemoglobin A1c (HbA1c) in patients with renal impairment is sparse.  This meta-analysis seeks to determine the effect of DPP-4I on HbA1c in patients with chronic kidney disease (CKD). METHODS: Multiple databases using the generic name of each DPP4I plus the following search terms “renal”, "renal impairment", chronic kidney disease”, “dialysis”, were queried for clinical trial data. Qualitative assessment and quantitative analyses were performed. RESULTS: Eleven citations met inclusion criteria.  Studies included 1,704 participants (10.7% on dialysis), 48-79 years of age, 56% men, 56% Caucasians. Four studies compared DPP4I with sulfonylurea (glipizide or glimepiride), five compared DPP4I with placebo, two compared DPP4I with placebo for initial 12-weeks and then switched to sulfonylurea for 40-42 weeks.  Meta-analysis showed DPP-4I caused a modest but significant reduction in HbA1c of 0.46% [95% Confidence Interval (CI) -0.58, -0.33], p<0.00001, (I= 12%), over 12-54 weeks (in patients not on dialysis). In placebo-comparator studies, reduction in HbA1c over 12-24 weeks was -0.54% [95%CI -0.67, -0.40], p<0.00001, without heterogeneity.  In sulfonylurea-comparator studies, DPP-4I did not significantly reduce HbA1c at week 24 (-0.09 [95%CI -0.26, 0.09]) but caused a small but significant reduction by weeks 52-54 (-0.19% [95%CI -0.37, -0.00], p=0.04), without heterogeneity.  In patients on dialysis, with either comparator (placebo or glipizide), DPP4I did not significantly reduce HbA1c after 52-54 weeks (0.11 [95%CI -0.20, 0.41]). CONCLUSIONS: DPP4I in patients with moderate-severe renal impairment is associated with a modest reduction of HbA1c versus placebo, but not when compared with sulfonylureas or when used in patients on dialysis.  It is unclear if this modest reduction is worth the high cost of DPP4I in patients with CKD.