title: Renal Effects of DPP-4 Inhibitor Sitagliptin or GLP-1 Receptor Agonist Liraglutide in Overweight Patients With Type 2 Diabetes: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial.
abstract: To investigate effects of dipeptidyl peptidase-4 inhibitor (DPP-4I) sitagliptin or glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide treatment on renal hemodynamics, tubular functions, and markers of renal damage in overweight patients with type 2 diabetes without chronic kidney disease (CKD).
  
  
  
  In this 12-week, randomized, double-blind trial, 55 insulin-naïve patients with type 2 diabetes (mean ± SEM: age 63 ± 7 years, BMI 31.8 ± 4.1 kg/m2, glomerular filtration rate [GFR] 83 ± 16 mL/min/1.73 m2; median [interquartile range]: albumin-to-creatinine ratio (ACR) 1.09 mg/mmol [0.47-3.31]) received sitagliptin (100 mg/day), liraglutide (1.8 mg/day), or matching placebos. GFR (primary end point) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippuric acid clearance, respectively. Intrarenal hemodynamic variables were estimated. Absolute and fractional excretions of sodium (FENa), potassium, and urea (FEU) and renal damage markers (ACR, neutrophil gelatinase-associated lipocalin [NGAL], and kidney injury molecule-1 [KIM-1]) were measured. Plasma renin concentration (PRC) and glycated hemoglobin (HbA1c) were assessed. At weeks 2 and 6, estimated GFR and fractional electrolyte excretions were determined.
  
  
  
  At week 12, GFR was not affected by sitagliptin (-6 mL/min/1.73 m2[95% CI -14 to 3], P = 0.17) or liraglutide (+3 mL/min/1.73 m2[-5 to 11], P = 0.46), compared with placebo. Sitagliptin modestly reduced estimated glomerular hydraulic pressure (PGLO; P = 0.043). ERPF, other intrarenal hemodynamic variables, renal damage markers, and PRC did not change for both treatments. Both agents reduced HbA1c. Only at week 2, sitagliptin increased FENaand FEU(P = 0.005).
  
  
  
  Twelve-week treatment with sitagliptin or liraglutide does not affect measured renal hemodynamics. No sustained changes in tubular functions or alteration in renal damage markers were observed. The validity and clinical relevance of the slight sitagliptin-induced PGLOreduction remains speculative.
authors: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands l.tonneijck@vumc.nl.
authors: Lennart
authors: L
authors: Tonneijck
authors: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors: Mark M
authors: MM
authors: Smits
authors: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors: Marcel H A
authors: MH
authors: Muskiet
authors: Department of Health Sciences and the EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, the Netherlands.|Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands.
authors: Trynke
authors: T
authors: Hoekstra
authors: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors: Mark H H
authors: MH
authors: Kramer
authors: Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors: A H Jan
authors: AH
authors: Danser
authors: Department of Nephrology, VU University Medical Center, Amsterdam, the Netherlands.
authors: Piet M
authors: PM
authors: Ter Wee
authors: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors: Michaela
authors: M
authors: Diamant
authors: Department of Nephrology and Hypertension, University Medical Center, Utrecht, the Netherlands.
authors: Jaap A
authors: JA
authors: Joles
authors: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors: Daniël H
authors: DH
authors: van Raalte
mesh_terms: D000368:Aged; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D007668:Kidney / Q000187:drug effects*; D000069450:Liraglutide / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000150:complications; D011188:Potassium / Q000652:urine; D012083:Renin / Q000097:blood; D000068900:Sitagliptin Phosphate / Q000008:administration & dosage / Q000009:adverse effects*; D012964:Sodium / Q000652:urine; D016896:Treatment Outcome; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069450:Liraglutide; D011188:Potassium; D012083:Renin; D000068900:Sitagliptin Phosphate; D012964:Sodium; D000097789:Glucagon-Like Peptide-1 Receptor Agonists