Effect of Saxagliptin on Renal Outcomes in the SAVOR-TIMI 53 Trial
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Open Access
- 17 October 2016
- journal article
- research article
- Published by American Diabetes Association in Diabetes Care
- Vol. 40 (1), 69-76
- https://doi.org/10.2337/dc16-0621
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] 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 −19.3 mg/g (P = 0.033) for estimated glomerular filtration rate (eGFR) >50 mL/min/body surface area per 1.73 m2 (BSA), −105 mg/g (P = 0.011) for 50 ≥ eGFR ≥ 30 mL/min/BSA, and −245.2 mg/g (P = 0.086) for eGFR 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.Keywords
This publication has 35 references indexed in Scilit:
- Diabetic Kidney Disease: A Report From an ADA Consensus ConferenceDiabetes Care, 2014
- Proteinuria should be used as a surrogate in CKDNature Reviews Nephrology, 2012
- Initial Angiotensin Receptor Blockade–Induced Decrease in Albuminuria Is Associated With Long-Term Renal Outcome in Type 2 Diabetic Patients With MicroalbuminuriaDiabetes Care, 2011
- Reduction in Microalbuminuria as an Integrated Indicator for Renal and Cardiovascular Risk Reduction in Patients With Type 2 DiabetesDiabetes, 2007
- Microalbuminuria as an Early Marker for Cardiovascular DiseaseJournal of the American Society of Nephrology, 2006
- The Relationship Between Magnitude of Proteinuria Reduction and Risk of End-stage Renal DiseaseArchives of Internal Medicine, 2005
- Diabetic nephropathy: Linking histology, cell biology, and geneticsKidney International, 2004
- Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: Lessons from RENAALKidney International, 2004
- Development and progression of nephropathy in type 2 diabetes: The United Kingdom Prospective Diabetes Study (UKPDS 64)Kidney International, 2003
- Albuminuria and Risk of Cardiovascular Events, Death, and Heart Failure in Diabetic and Nondiabetic IndividualsJAMA, 2001