Efficiency and safety of DDP-4 inhibitor in treatment of type 2 diabetes with moderate and severe renal insufficiency: a systemic review and Meta-analysis

Abstract

Objectives Dipeptidyl peptidase-4(DDP-4) inhibitors were considered as an effective treatment choice in patients with type 2 diabetes and renal insufficiency, while its safety and tolerability still needed more confirmation. We performed A systematic review of the safety and efficiency of DDP-4 inhibitors in treatment of patients with type 2 diabetic with chronic kidney disease (CKD) were performed by Meta-analysis. Methods A systemic review of randomized controlled trials (RCTs) on DPP-4 inhibitors(including sitagliptin, saxagliptin, vildagliptin, linagliptin and teneligliptin) in type 2 diabetes with renal insufficiency was conducted.MEDLINE and EMBASE were searched until June 2015. RCTs or quasi-RCTs comparing the efficacy and/or safety outcome between DPP-4 inhibitors and placebo or an antihyperglycemic agent in diabetes patients with chronic renal disease were selected. Results In 13 evaluated articles, DPP-4 inhibitors lowered hemoglobin A1c (HbA1C) significantly. Subgroup of DPP-4 inhibitor VS Placebo resulted in a more obvious effect on HbA1c, while subgroup analysis among both patients with moderate and severe renal impairment including ESRD and dialysis still showed significant effect to decrease HbA1c (%); DPP-4 inhibitors showed little effect on FPG, even compared with placebo(P=0.86, I2=90%); For safety evaluation, DPP-4 inhibitors slightly increased risk of hypoglycemia (OR[95%CI]: 1.38 [1.07, 1.78], P=0.01, I2=0%) compared with placebo, while the risk decreased when compared with other hypoglycemic agents (OR[95%CI]: 0.46 [0.33, 0.65], P<0.0001, I2=31%). No significant difference in hypoglycemia was observed in both subgroups of moderate renal impairment and severe renal impairment including ESRD. Total AEs in DPP-4 inhibitor group also showed no difference compared with control, further analysis based on renal function also resulted in a similar effect without significant difference for moderate renal impairment subgroup and in severe renal impairment including ESRD and dialysis group; Similar odds risk were observed in drug related adverse events(OR[95%CI]: 0.93 [0.71, 1.22], P=0.6, I2=7%)and death(OR[95%CI]: 0.77 [0.47, 1.26], P=0.3, I2=0%) between DPP-4 inhibitors and control. Conclusions DPP-4 inhibitors are effective to reduce A1C with comparable safety profiles in diabetes patients with moderate to severe renal deficiency including ESRD and dialysis compared to placebo, while evidences from more controlled trials concentrating on particular population of patients with renal deficiency including dialysis are needed. Key words: Diabetes Mellitus, Type 2; Renal Insufficiency; Meta-Analysis