title: Effect of Saxagliptin on Renal Outcomes in the SAVOR-TIMI 53 Trial.
abstract: Dipeptidyl peptidase 4 inhibitors may have a protective effect in diabetic nephropathy.
  
  
  
  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.
  
  
  
  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 -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 <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.
  
  
  
  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.
authors: Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel.
authors: Ofri
authors: O
authors: Mosenzon
authors: Diabetes Unit, Endocrinology Service, Hadassah Hebrew University Hospital, Jerusalem, Israel.
authors: Gil
authors: G
authors: Leibowitz
authors: Thrombolysis in Myocardial Infarction (TIMI) Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors: Deepak L
authors: DL
authors: Bhatt
authors: Diabetes Unit, Endocrinology Service, Hadassah Hebrew University Hospital, Jerusalem, Israel.
authors: Avivit
authors: A
authors: Cahn
authors: MedImmune, Gaithersburg, MD.
authors: Boaz
authors: B
authors: Hirshberg
authors: Research and Development, AstraZeneca, Gaithersburg, MD.
authors: Cheryl
authors: C
authors: Wei
authors: Thrombolysis in Myocardial Infarction (TIMI) Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors: KyungAh
authors: K
authors: Im
authors: Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel.
authors: Aliza
authors: A
authors: Rozenberg
authors: Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel.
authors: Ilan
authors: I
authors: Yanuv
authors: Research and Development, AstraZeneca, Molndal, Sweden.
authors: Christina
authors: C
authors: Stahre
authors: Department of Primary Care and Public Health, Imperial College, London, U.K.
authors: Kausik K
authors: KK
authors: Ray
authors: Research and Development, AstraZeneca, Gaithersburg, MD.
authors: Nayyar
authors: N
authors: Iqbal
authors: Thrombolysis in Myocardial Infarction (TIMI) Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors: Eugene
authors: E
authors: Braunwald
authors: Thrombolysis in Myocardial Infarction (TIMI) Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors: Benjamin M
authors: BM
authors: Scirica
authors: Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel ntv502@netvision.net.il.
authors: Itamar
authors: I
authors: Raz
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000368:Aged; D000419:Albuminuria / Q000188:drug therapy* / Q000209:etiology; D001786:Blood Glucose / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology; D004151:Dipeptides / Q000008:administration & dosage*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000032:analysis
chemical_list: D001786:Blood Glucose; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D012709:Serum Albumin; C502994:saxagliptin; D003404:Creatinine; D000218:Adamantane