title: The effect of liraglutide on renal function: A randomized clinical trial.
abstract: Among patients with type 2 diabetes and albuminuria, cardiorenal morbidity and mortality are high despite multifactorial treatment. Short-term reduction in albuminuria is considered suggestive of long-term renoprotective effects. We evaluated the renal effects of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on top of multifactorial care, including renin-angiotensin-system (RAS)-inhibition.
  
  
  
  Randomized, double-blind, placebo-controlled, cross-over trial including patients with type 2 diabetes and persistent albuminuria (urinary albumin-to-creatinine ratio >30 mg/g) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. Patients received liraglutide (1.8 mg/d) and matched placebo for 12 weeks in a random order. The primary endpoint was change in 24-h urinary albumin excretion rate (UAER).
  
  
  
  A total of 32 patients were randomized and 27 completed the study. After placebo treatment, geometric mean (IQR) UAER was 199 (81-531) mg/24-h, mean (SD) measured GFR (mGFR) 75 (36) mL/min/1.73 m2, 24-h blood pressure 145/80 (15/8) mm Hg and HbA1c 61 (11) mmol/mol. Liraglutide reduced HbA1c by 8 (95% CI: 5; 11) mmol/mol (P < .001) and weight by 1.8 (95% CI: 0.2; 3.4) kg (P = .032) compared to placebo. Furthermore, liraglutide reduced UAER by 32 (95% CI: 7; 50)% ( P = .017) compared with placebo. The change in mGFR was -5 (95% CI: -11; 2) mL/min/1.73 m2( P = .15), and change in 24-h systolic blood pressure was -5 (95% CI: -10; 0) mm Hg ( P = .07). In multivariate regression models, change in UAER was associated with change in 24-h systolic blood pressure ( P = .025) but not with change in HbA1c, weight or mGFR ( P ≥ .14), overall model R2= .39.
  
  
  
  Our placebo-controlled randomized trial suggests that liraglutide has renoprotective effects on top of multifactorial treatment, including RAS-inhibition, in patients with type 2 diabetes and albuminuria.
authors.affiliation: Department of Diabetes Complications Research, Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Bernt J
authors.initials: BJ
authors.lastname: von Scholten
authors.affiliation: Department of Diabetes Complications Research, Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Frederik
authors.initials: F
authors.lastname: Persson
authors.affiliation: Department of Diabetes Complications Research, Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Signe
authors.initials: S
authors.lastname: Rosenlund
authors.affiliation: Department of Clinical Physiology & Nuclear Medicine & PET, Rigshospitalet, Glostrup Hospital, Glostrup, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Hovind
authors.affiliation: Department of Endocrinology, Herlev University Hospital, Herlev, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Faber
authors.affiliation: Department of Diabetes Complications Research, Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Tine W
authors.initials: TW
authors.lastname: Hansen
authors.affiliation: Department of Diabetes Complications Research, Steno Diabetes Center, Gentofte, Denmark.|Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.|Health, Aarhus University, Aarhus, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
mesh_terms: D000368:Aged; D000419:Albuminuria; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D003404:Creatinine / Q000652:urine*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069450:Liraglutide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D012083:Renin / Q000378:metabolism
chemical_list: D000450:Aldosterone; D000804:Angiotensin II; D001786:Blood Glucose; D003404:Creatinine; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D012083:Renin; C517652:hemoglobin A1c protein, human
keywords: 
  GLP-1; diabetic nephropathy; liraglutide; randomized trial