Effect of saxagliptin on renal outcomes in the SAVOR-TIMI 53 trial

Ofri Mosenzon, Gil Leibowitz, Deepak L. Bhatt, Avivit Cahn, Boaz Hirshberg, Cheryl Wei, Kyung Ah Im, Aliza Rozenberg, Ilan Yanuv, Christina Stahre, Kausik K. Ray, Nayyar Iqbal, Eugene Braunwald, Benjamin M. Scirica, Itamar Raz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

198 Scopus citations

Abstract

OBJECTIVE Dipeptidyl peptidase 4 inhibitors may have a protective effect in diabetic nephropathy. RESEARCH DESIGN AND METHODS We studied renal outcomes of 16,492 patients with type 2 diabetes, randomized to saxagliptin versus placebo and followed for a median of 2.1 years in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial. RESULTS At baseline, 9,696 (58.8%) subjects had normoalbuminuria (albumin/creatinine ratio [ACR] <30 mg/g), 4,426 (26.8%) had microalbuminuria (ACR 30-300 mg/g), and 1,638 (9.9%) had macroalbuminuria (ACR >300 mg/g). Treatment with saxagliptin was associated with improvement in and/or less deterioration in ACR categories from baseline to end of trial (EOT) (P = 0.021, P < 0.001, and P = 0.049 for individuals with baseline normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively). At 2 years, the difference in mean ACR change between saxagliptin and placebo arms was 219.3 mg/g (P = 0.033) for estimated glomerular filtration rate (eGFR) >50 mL/min/body surface area per 1.73 m2 (BSA), 2105 mg/g (P = 0.011) for 50 ≥ eGFR ≥ 30 mL/min/BSA, and 2245.2 mg/g (P = 0.086) for eGFR <30 mL/min/BSA. Analyzing ACR as a continuous variable showed reduction in ACR with saxagliptin (1 year, P < 0.0001; 2 years, P = 0.0143; and EOT, P = 0.0158). The change in ACR did not correlate with that in HbA1c (r = 0.041, 0.052, and 0.036; 1 year, 2 years, and EOT, respectively). The change in eGFR was similar in the saxagliptin and placebo groups. Safety renal outcomes, including doubling of serum creatinine, initiation of chronic dialysis, renal transplantation, or serum creatinine >6.0 mg/dL, were similar as well. CONCLUSIONS Treatment with saxagliptin improved ACR, even in the normoalbuminuric range, without affecting eGFR. The beneficial effect of saxagliptin on albuminuria could not be explained by its effect on glycemic control.

Original languageAmerican English
Pages (from-to)69-76
Number of pages8
JournalDiabetes Care
Volume40
Issue number1
DOIs
StatePublished - 1 Jan 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 by the American Diabetes Association.

Fingerprint

Dive into the research topics of 'Effect of saxagliptin on renal outcomes in the SAVOR-TIMI 53 trial'. Together they form a unique fingerprint.

Cite this