Saxagliptin and vildagliptin lowered albuminuria in patients with diabetes and hypertension independent on glycaemic control

Abstract

Background Preclinical data illustrated that the dipeptidyl peptidase‐4(DPP‐4) inhibitors did lower urinary albumin excretion in diabetes‐induced rats. We evaluated the effects of saxagliptin and vildagliptin on albuminuria in patients with diabetic nephropathy on top of the renin‐angiotensin‐aldosterone system (RAAS) blockade therapy. Methods This study included 120 patients with type 2 diabetes (T2D), hypertension, and prevalent albuminuria [defined as urine albumin‐to‐creatinine ratio (UACR) 30‐3000mg/g creatinine] on a stable dose of olmesartan as a standard RAAS blocker for diabetic nephropathy. Patients were assigned to receive either of saxagliptin 5mg/day (n = 40), vildagliptin 100mg/day (n = 40), or traditional antidiabetic therapy as control patients (n = 40) for 12 weeks. Results Each of saxagliptin and vildagliptin significantly reduced albuminuria after 12 weeks, with mean percentage changes (%) of −57.9% [95% confidence interval (CI) −66.1 to −49.8], and −55.2% (95% CI −64.9 to −45.4); P < .001, respectively, compared with the control group. Significantly, saxagliptin shifted higher proportions of patients towards lower albuminuria categories (P < .001) compared with vildagliptin despite a similar UACR rate of changes. Results of binary logistic models confirmed that the change in UACR because saxagliptin was independent of changes in systolic blood pressure (SBP), glycated hemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), or body weight (overall regression: P = .002, R2 = 0.398) vs control. Likewise, vildagliptin reduced UACR independently on other confounders (overall regression: P = .002, R2 = 0.388). Furthermore, no significant correlation was observed between the change in UACR and changes in HbA1c, SBP or eGFR with either saxagliptin or vildagliptin (Pearson coefficients: 0.203, 0.143, −0.190; P > .05, and 0.003, 0.241, 0.019; P > .05, respectively). Conclusions DPP‐4 inhibitors, saxagliptin, and vildagliptin, resulted in substantial reductions in albuminuria in patients with T2D and hypertension on top of RAAS blockade after short term therapy independently on glycaemic or hemodynamic changes. Saxagliptin was superior to vildagliptin in albuminuria‐categorical shifting.

Renoprotective Effects of DPP-4 Inhibitors

“…A recent RCT demonstrated that the administration of saxagliptin and vildagliptin for 12 weeks significantly reduced the albuminuria rate by 57.9% (95% CI: 66.1-49.8%) and 55.2% (95% CI 64.9-45.4%), respectively, compared with the control group in T2D subjects. Interestingly, these observations were not associated with HbA1c changes [119].…”

Effect of DPP-4i inhibitors on renal function in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials

“…Evidence showed that saxagliptin and vildagliptin significantly reduced albuminuria, respectively, in diabetic patients with hypertension. Saxagliptin might present a stronger effect on reducing albuminuria compared to vildagliptin, an action independent of glycaemic control [ 19 ]. In fact, administration of saxagliptin ameliorated microalbuminuria in patients with or without renal impairment [ 20 ].…”