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

Bernt J von Scholten; Frederik Persson; Signe Rosenlund; Peter Hovind; Jens Faber; Tine W Hansen; Peter Rossing

doi:10.1111/dom.12808

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

Bernt J von Scholten, Frederik Persson, Signe Rosenlund, Peter Hovind, Jens Faber, Tine W Hansen, Peter Rossing

Department of Clinical Medicine

47 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Diabetes, Obesity and Metabolism
Volume	19
Issue number	2
Pages (from-to)	239-247
Number of pages	9
ISSN	1462-8902
DOIs	https://doi.org/10.1111/dom.12808
Publication status	Published - 1 Feb 2017

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@article{8d19389c743b48d282722cc2c62ea965,

title = "The effect of liraglutide on renal function: A randomized clinical trial",

abstract = "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.",

author = "{von Scholten}, {Bernt J} and Frederik Persson and Signe Rosenlund and Peter Hovind and Jens Faber and Hansen, {Tine W} and Peter Rossing",

note = "{\textcopyright} 2016 John Wiley & Sons Ltd.",

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doi = "10.1111/dom.12808",

language = "English",

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TY - JOUR

T1 - The effect of liraglutide on renal function

T2 - A randomized clinical trial

AU - von Scholten, Bernt J

AU - Persson, Frederik

AU - Rosenlund, Signe

AU - Hovind, Peter

AU - Faber, Jens

AU - Hansen, Tine W

AU - Rossing, Peter

PY - 2017/2/1

Y1 - 2017/2/1

N2 - 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.

AB - 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.

U2 - 10.1111/dom.12808

DO - 10.1111/dom.12808

M3 - Journal article

C2 - 27753201

SN - 1462-8902

VL - 19

SP - 239

EP - 247

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

IS - 2

ER -

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

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