title: Pleiotropic effects of liraglutide treatment on renal risk factors in type 2 diabetes: Individual effects of treatment.
abstract: Management of diabetic nephropathy includes reduction of albuminuria, blood pressure and weight. The GLP-1 receptor agonist liraglutide may possess these pleiotropic effects in addition to the glucose lowering effect. We aimed to elucidate the individual liraglutide treatment response by determining if high responders (highest reduction) in each risk factor also had high response in other renal risk factors (cross-dependency).
  
  
  
  Open-label study: 31 type 2 diabetics treated with liraglutide for 7weeks. After 3weeks washout 23 re-started treatment and were followed for 1year. HbA1c, weight, systolic blood pressure (SBP), urinary albumin excretion rate (UAER) and mGFR (51Cr-EDTA) were evaluated. Changes in high (Q4) vs. low responders (Q1-Q3) were compared for each renal risk factor. The effects of treatment/off treatment/re-treatment (off-on/off-on effect) were evaluated to account for random effects.
  
  
  
  After 7weeks HbA1cwas reduced 6(95% CI: 3;9)mmol/mol, weight 2.5(1.8;3.2)kg, SBP 4(-1;9)mmHg, UAER 30(12;44)% and mGFR 11(7;14)ml/min per 1.73m2. mGFR high responders had a significant reduction in weight compared to low responders (4.3 vs. 1.9kg; p=0.002). SBP high responders had a tendency of a higher reduction in UAER compared to low responders (47 vs. 23%, p=0.14). No cross-dependency was observed in any of the other renal risk factors (p≥0.16). Treatment response did not differ after 7weeks and 1year (p≥0.12).
  
  
  
  Liraglutide possesses pleiotropic effects on renal risk factors. On patient level, effect on the individual risk factor cannot be anticipated based on response in other risk factors. Response when re-starting treatment did not differ, indicating that our primary findings were not random.
authors: Steno Diabetes Center, Gentofte, Denmark. Electronic address: ehnp@steno.dk.
authors: Emilie Hein
authors: EH
authors: Zobel
authors: Steno Diabetes Center, Gentofte, Denmark.
authors: Bernt Johan
authors: BJ
authors: von Scholten
authors: Steno Diabetes Center, Gentofte, Denmark.
authors: Morten
authors: M
authors: Lindhardt
authors: Steno Diabetes Center, Gentofte, Denmark.
authors: Frederik
authors: F
authors: Persson
authors: Steno Diabetes Center, Gentofte, Denmark.
authors: Tine Willum
authors: TW
authors: Hansen
authors: Steno Diabetes Center, Gentofte, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, DK; Health, Aarhus University, Aarhus, DK.
authors: Peter
authors: P
authors: Rossing
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000517:prevention & control*; D004198:Disease Susceptibility; D004351:Drug Resistance; D005260:Female; D005919:Glomerular Filtration Rate; D052216:Glucagon-Like Peptide 1 / Q000819:agonists* / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D000069450:Liraglutide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D015203:Reproducibility of Results; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069450:Liraglutide; C517652:hemoglobin A1c protein, human
keywords: Diabetic nephropathy; GLP-1; Glomerular filtration rate; Liraglutide; Type 2 diabetes