Effects of liraglutide on cardiovascular risk biomarkers in patients with type 2 diabetes and albuminuria: A sub‐analysis of a randomized, placebo‐controlled, double‐blind, crossover trial
Abstract
We assessed the effects of liraglutide treatment on five cardiovascular risk biomarkers, reflecting different pathophysiology: tumour necrosis factor ( TNF )‐α; soluble urokinase plasminogen activator receptor ( suPAR ); mid‐regional pro‐adrenomedullin ( MR‐proADM ); mid‐regional pro‐atrial natriuretic peptide ( MR‐proANP ); and copeptin, in people with type 2 diabetes with albuminuria. In a randomized, double‐blind, placebo‐controlled, crossover trial we enrolled people with type 2 diabetes and persistent albuminuria (urinary albumin‐to‐creatinine ratio [ UACR ] >30 mg/g) and estimated glomerular filtration rate ( eGFR ) ≥30 mL /min/1.73 m 2 . Participants received liraglutide (1.8 mg/d) and matched placebo for 12 weeks, in random order. The primary endpoint was change in albuminuria; this was a prespecified sub‐study. A total of 32 participants were randomized, of whom 27 completed the study. TNF ‐α level was 12% (95% confidence interval [ CI ] 3; 20) lower after liraglutide treatment compared with placebo ( P = .012); MR‐proADM level was 4% (95% CI 0; 8) lower after liraglutide treatment compared with placebo ( P = .038), and MR‐proANP level was 13% (95% CI 4; 21) lower after liraglutide treatment compared with placebo ( P = .006). In the present study, we showed anti‐inflammatory effects of liraglutide treatment, reflected in reductions in levels of TNF ‐α and MR‐proADM , while the reduction in MR‐proANP levels may represent a clinically relevant benefit with regard to heart failure.
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Liraglutide significantly lowered TNF-alpha in one study.
“while liraglutide significantly lowered TNF-α in one study (18)”
Individual randomized controlled trial findings on the effects of GLP-1 receptor agonists on inflammatory biomarkers are inconsistent.
“The findings, however, have been inconsistent. Some studies report significant reductions in TNF-α and CRP with GLP-1 RA therapy compared to placebo or other antidiabetic medications (6, 15, 17, 18), while others show non-significant or conflicting results (19, 20).”
Von Scholten et al. showed that liraglutide significantly reduced TNF-α and improved endothelial dysfunction indicators in T2D patients with chronic albuminuria.
“In a particular study of T2D patients with chronic albuminuria, a high-risk group, Von Scholten et al. (18) showed that liraglutide significantly reduced TNF-α and improved endothelial dysfunction indicators.”
In this study, several studies found that improvements in inflammatory markers were accompanied by decreases in albuminuria.
“In our study, several studies found that improvements in inflammatory markers were accompanied by decreases in albuminuria (6, 15, 17, 18).”
The antihypertensive effect of liraglutide might not be driven by MR-proANP levels, but rather by increased natriuresis.
“which suggests that the antihypertensive effect of liraglutide might not be driven by MR-proANP levels, but rather to increased natriuresis”
From Effect of liraglutide on atrial natriuretic peptide, adrenomedullin, and copeptin in PCOS (2018) · cites this paper as [33]
In human studies on T2D patients, liraglutide treatment led to increased natriuresis.
“In contrast, in human studies on T2D patients, liraglutide treatment led to reduction in both MR-proANP and blood pressure, but also increased natriuresis (33)”
From Effect of liraglutide on atrial natriuretic peptide, adrenomedullin, and copeptin in PCOS (2018) · cites this paper as [33]
In human studies on T2D patients, liraglutide treatment led to reduction in blood pressure.
“In contrast, in human studies on T2D patients, liraglutide treatment led to reduction in both MR-proANP and blood pressure, but also increased natriuresis (33)”
From Effect of liraglutide on atrial natriuretic peptide, adrenomedullin, and copeptin in PCOS (2018) · cites this paper as [33]
In human studies on T2D patients, liraglutide treatment led to reduction in MR-proANP.
“In contrast, in human studies on T2D patients, liraglutide treatment led to reduction in both MR-proANP and blood pressure, but also increased natriuresis (33)”
From Effect of liraglutide on atrial natriuretic peptide, adrenomedullin, and copeptin in PCOS (2018) · cites this paper as [33]
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“In the present study, we confirm that liraglutide reduces MR-proANP levels, which might reflect reduced atrial and ventricular distention, and perhaps a prognostic benefit in heart failure, although this was not identified as significant in the LEADER study.(11) We observed a powerful association between reduction in…”
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Effect of liraglutide on atrial natriuretic peptide, adrenomedullin, and copeptin in PCOS
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- Authors
- von Scholten, B. J., Persson, F., Rosenlund, S., Eugen‐Olsen, J., Pielak, T., Faber, J., Hansen, T. W., & Rossing, P.
- Affiliations
- Department of Diabetes Complications Research, Steno Diabetes Center Copenhagen Gentofte Denmark
- Steno Diabetes Center Copenhagen (DK)
- Hvidovre Hospital (DK)
- Nutopi Sp. z o.o. Poznan Poland
- Herlev Hospital (DK)
- University of Copenhagen (DK)
- ORCID
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2017-03-02
- Volume
- 19
- Issue
- 6
- Pages
- 901-905
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W2591646518
- Cited by
- 60
- References
- 2
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 6 · 2023: 2 · 2022: 5 · 2021: 9 · 2020: 5 · 2019: 6 · 2018: 5 · 2017: 5
- FWCI
- 4.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Novo Nordisk A/S, Bagsvaerd, Denmark
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- liraglutide, type 2 diabetes, albuminuria, cardiovascular risk markers, TNF-α, mid-regional pro-adrenomedullin, MR-proANP, copeptin, soluble urokinase plasminogen activator receptor, anti-inflammatory activity, heart failure, albumin-creatinine ratio
- MeSH terms
- Liraglutide, Aged, Albuminuria, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Glycopeptides, Humans, Hypoglycemic Agents, Male, Middle Aged, Atrial Natriuretic Factor, Peptide Fragments, Protein Precursors, Risk Factors, Tumor Necrosis Factor-alpha, Biomarkers, Cross-Over Studies, Adrenomedullin, Receptors, Urokinase Plasminogen Activator
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