TY - JOUR
T1 - Renal effects of DPP-4 inhibitor sitagliptin or GLP-1 receptor agonist liraglutide in overweight patients with type 2 diabetes
T2 - A 12-week, randomized, double-blind, placebo-controlled trial
AU - Tonneijck, Lennart
AU - Smits, Mark M.
AU - Muskiet, Marcel H A
AU - Hoekstra, Trynke
AU - Kramer, Mark H H
AU - Danser, A. H Jan
AU - Ter Wee, Piet M.
AU - Diamant, Michaela
AU - Joles, Jaap A.
AU - Van Raalte, Daniël H.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - OBJECTIVE 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). RESEARCH DESIGN AND METHODS In this 12-week, randomized, double-blind trial, 55 insulin-naïve patients with type 2 diabetes (mean6SEM: age 6367 years, BMI 31.864.1 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 paraaminohippuric 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 (HbA>1c>)were assessed. Atweeks 2 and 6, estimated GFR and fractional electrolyte excretions were determined. RESULTS At week 12, GFR was not affected by sitagliptin (26 mL/min/1.73 m2 [95% CI 214 to 3], P = 0.17) or liraglutide (+3 mL/min/1.73 m2 [25 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 HbA>1c>. Only at week 2, sitagliptin increased FENa and FEU (P = 0.005).CONCLUSIONS 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 PGLO reduction remains speculative.
AB - OBJECTIVE 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). RESEARCH DESIGN AND METHODS In this 12-week, randomized, double-blind trial, 55 insulin-naïve patients with type 2 diabetes (mean6SEM: age 6367 years, BMI 31.864.1 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 paraaminohippuric 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 (HbA>1c>)were assessed. Atweeks 2 and 6, estimated GFR and fractional electrolyte excretions were determined. RESULTS At week 12, GFR was not affected by sitagliptin (26 mL/min/1.73 m2 [95% CI 214 to 3], P = 0.17) or liraglutide (+3 mL/min/1.73 m2 [25 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 HbA>1c>. Only at week 2, sitagliptin increased FENa and FEU (P = 0.005).CONCLUSIONS 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 PGLO reduction remains speculative.
UR - http://www.scopus.com/inward/record.url?scp=84994361897&partnerID=8YFLogxK
U2 - 10.2337/dc16-1371
DO - 10.2337/dc16-1371
M3 - Article
C2 - 27585605
AN - SCOPUS:84994361897
SN - 0149-5992
VL - 39
SP - 2042
EP - 2050
JO - Diabetes Care
JF - Diabetes Care
IS - 11
ER -