Dapagliflozin, inflammation and left ventricular remodelling in patients with type 2 diabetes and left ventricular hypertrophy.
Humans
Glucosides
/ therapeutic use
Benzhydryl Compounds
/ therapeutic use
Hypertrophy, Left Ventricular
/ physiopathology
Diabetes Mellitus, Type 2
/ drug therapy
Ventricular Remodeling
/ drug effects
Male
Female
Sodium-Glucose Transporter 2 Inhibitors
/ therapeutic use
Middle Aged
Ventricular Function, Left
/ drug effects
Treatment Outcome
Inflammation Mediators
/ blood
Biomarkers
/ blood
Aged
Time Factors
Inflammation
/ drug therapy
Double-Blind Method
Anti-Inflammatory Agents
/ therapeutic use
Cytokines
/ blood
Cytokines
Global longitudinal strain
Heart failure
Inflammation
Left ventricle hypertrophy
Sodium-glucose co-transporter 2 inhibitors
Journal
BMC cardiovascular disorders
ISSN: 1471-2261
Titre abrégé: BMC Cardiovasc Disord
Pays: England
ID NLM: 100968539
Informations de publication
Date de publication:
12 Jul 2024
12 Jul 2024
Historique:
received:
09
04
2024
accepted:
28
06
2024
medline:
13
7
2024
pubmed:
13
7
2024
entrez:
12
7
2024
Statut:
epublish
Résumé
Sodium-glucose co-transporter 2 (SGLT2) inhibitors have beneficial effects in heart failure (HF), including reverse remodelling, but the mechanisms by which these benefits are conferred are unclear. Inflammation is implicated in the pathophysiology of heart failure (HF) and there are some pre-clinical data suggesting that SGLT2 inhibitors may reduce inflammation. There is however a lack of clinical data. The aim of our study was to investigate whether improvements in cardiac remodelling caused by dapagliflozin in individuals with type 2 diabetes (T2D) and left ventricular hypertrophy (LVH) were associated with its effects on inflammation. We measured C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin 6 (IL-6), and interleukin 10 (IL-10) and neutrophil-to-lymphocyte ratio (NLR) in plasma samples of 60 patients with T2D and left ventricular hypertrophy (LVH) but without symptomatic HF from the DAPA-LVH trial in which participants were randomised dapagliflozin 10 mg daily or placebo for 12 months and underwent cardiac magnetic resonance imaging (CMR) at baseline and end of treatment. The primary analysis was to investigate the effect of dapagliflozin on inflammation and to assess the relationships between changes in inflammatory markers and LV mass and global longitudinal strain (GLS) and whether the effect of dapagliflozin on LV mass and GLS was modulated by baseline levels of inflammation. Following 12 months of treatment dapagliflozin significantly reduced CRP compared to placebo (mean difference of -1.96; 95% CI -3.68 to -0.24, p = 0.026). There were no significant statistical changes in other inflammatory markers. There were modest correlations between improvements in GLS and reduced inflammation (NLR (r = 0.311), IL-1β (r = 0.246), TNF-α (r = 0.230)) at 12 months. Dapagliflozin caused a significant reduction in CRP compared to placebo. There were correlations between reductions in inflammatory markers including IL-1β and improvements in global longitudinal strain (but not reduced LV mass). Reductions in systemic inflammation might play a contributory role in the cardiovascular benefits of dapagliflozin. Clinicaltrials.gov NCT02956811 (06/11/2016).
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Sodium-glucose co-transporter 2 (SGLT2) inhibitors have beneficial effects in heart failure (HF), including reverse remodelling, but the mechanisms by which these benefits are conferred are unclear. Inflammation is implicated in the pathophysiology of heart failure (HF) and there are some pre-clinical data suggesting that SGLT2 inhibitors may reduce inflammation. There is however a lack of clinical data. The aim of our study was to investigate whether improvements in cardiac remodelling caused by dapagliflozin in individuals with type 2 diabetes (T2D) and left ventricular hypertrophy (LVH) were associated with its effects on inflammation.
METHODS
METHODS
We measured C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin 6 (IL-6), and interleukin 10 (IL-10) and neutrophil-to-lymphocyte ratio (NLR) in plasma samples of 60 patients with T2D and left ventricular hypertrophy (LVH) but without symptomatic HF from the DAPA-LVH trial in which participants were randomised dapagliflozin 10 mg daily or placebo for 12 months and underwent cardiac magnetic resonance imaging (CMR) at baseline and end of treatment. The primary analysis was to investigate the effect of dapagliflozin on inflammation and to assess the relationships between changes in inflammatory markers and LV mass and global longitudinal strain (GLS) and whether the effect of dapagliflozin on LV mass and GLS was modulated by baseline levels of inflammation.
RESULTS
RESULTS
Following 12 months of treatment dapagliflozin significantly reduced CRP compared to placebo (mean difference of -1.96; 95% CI -3.68 to -0.24, p = 0.026). There were no significant statistical changes in other inflammatory markers. There were modest correlations between improvements in GLS and reduced inflammation (NLR (r = 0.311), IL-1β (r = 0.246), TNF-α (r = 0.230)) at 12 months.
CONCLUSIONS
CONCLUSIONS
Dapagliflozin caused a significant reduction in CRP compared to placebo. There were correlations between reductions in inflammatory markers including IL-1β and improvements in global longitudinal strain (but not reduced LV mass). Reductions in systemic inflammation might play a contributory role in the cardiovascular benefits of dapagliflozin.
TRIAL REGISTRATION
BACKGROUND
Clinicaltrials.gov NCT02956811 (06/11/2016).
Identifiants
pubmed: 38997620
doi: 10.1186/s12872-024-04022-7
pii: 10.1186/s12872-024-04022-7
doi:
Substances chimiques
Glucosides
0
dapagliflozin
1ULL0QJ8UC
Benzhydryl Compounds
0
Sodium-Glucose Transporter 2 Inhibitors
0
Inflammation Mediators
0
Biomarkers
0
Anti-Inflammatory Agents
0
Cytokines
0
Banques de données
ClinicalTrials.gov
['NCT02956811']
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
356Subventions
Organisme : AstraZeneca
ID : ESR-14-1016
Organisme : Tenovus Scotland
ID : T20-58
Organisme : British Heart Foundation
ID : FS/ICRF/24/26101
Pays : United Kingdom
Informations de copyright
© 2024. The Author(s).
Références
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