The effect of liraglutide on renal function: A randomized clinical trial

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DOI

  • Bernt J. von Scholten, Steno Diabetes Center
  • ,
  • Frederik Persson, Steno Diabetes Center
  • ,
  • Signe Rosenlund, Steno Diabetes Center
  • ,
  • Peter Hovind, Rigshospitalet
  • ,
  • Jens Faber
  • ,
  • Tine W. Hansen, Steno Diabetes Center
  • ,
  • Peter Rossing, Department of Diabetes Complications Research, Steno Diabetes Center, Department of Clinical Medicine, University of Copenhagen

Aims: 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. Materials and methods: 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). Results: 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 R 2 =.39. Conclusions: 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.

OriginalsprogEngelsk
TidsskriftDiabetes, Obesity and Metabolism
Vol/bind19
Nummer2
Sider (fra-til)239-247
Antal sider9
ISSN1462-8902
DOI
StatusUdgivet - feb. 2017

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