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Effects of dapaglif...
Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes: a double-blind randomised placebo-controlled study
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- Eriksson, Jan W. (author)
- Uppsala universitet,Klinisk diabetologi och metabolism
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- Lundkvist, Per (author)
- Uppsala universitet,Klinisk diabetologi och metabolism
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- Jansson, Per-Anders, 1961 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,Univ Gothenburg, Dept Mol & Clin Med, Gothenburg, Sweden.
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- Johansson, L. (author)
- Antaros Med AB, Gothenburg, Sweden.
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- Kvarnstrom, M. (author)
- AstraZeneca Gothenburg, Gothenburg, Sweden.
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- Moris, L. (author)
- Karolinska Univ Hosp, ICarolinska Trial Alliance, Stockholm, Sweden.
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- Miliotis, T. (author)
- AstraZeneca Gothenburg, Gothenburg, Sweden.
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- Forsberg, G. B. (author)
- AstraZeneca Gothenburg, Gothenburg, Sweden.
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- Risérus, Ulf, 1967- (author)
- Uppsala universitet,Klinisk nutrition och metabolism
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- Lind, Lars (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Klinisk nutrition och metabolism
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- Oscarsson, J. (author)
- AstraZeneca Gothenburg, Gothenburg, Sweden.
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(creator_code:org_t)
- 2018-07-03
- 2018
- English.
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 61:9, s. 1923-1934
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https://doi.org/10.1...
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Abstract
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- Aims/hypothesis The EFFECT-II study aimed to investigate the effects of dapagliflozin and omega-3 (n-3) carboxylic acids (OM-3CA). individually or combined, on liver fat content in individuals with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Methods This randomised placebo-controlled double-blind parallel-group study was performed at five clinical research centres at university hospitals in Sweden. 84 participants with type 2 diabetes and NAFLD were randomly assigned 1:1:1:1 to four treatments by a centralised randomisation system, and all participants as well as investigators and staff involved in the study conduct and analyses were blinded to treatments. Each group received oral doses of one of the following: 10 mg dapagliflozin (n = 21). 4 g OM3-CA (n = 20), a combination of both (n = 22) or placebo (n = 21). The primary endpoint was liver fat content assessed by MRI (proton density fat fraction [PDFF]) and, in addition, total liver volume and markers of glucose and lipid metabolism as well as of hepatocyte injury and oxidative stress were assessed at baseline and after 12 weeks of treatment (completion of the trial). Results Participants had a mean age of 65.5 years (SD 5.9), BMI 31.2 kg/m(2) (3.5) and liver PDFF 18% (9.3). All active treatments significantly reduced liver PDFF from baseline, relative changes: OM-3CA, -15%; dapagliflozin, -13%; OM-3CA + dapagliflozin, -21%. Only the combination treatment reduced liver PDFF (p = 0.046) and total liver fat volume (relative change, -24%,p = 0.037) in comparison with placebo. There was an interaction between the PNPLA31148M polymorphism and change in liver PDFF in the active treatment groups (p = 0.03). Dapagliflozin monotherapy, but not the combination with OM-3CA, reduced the levels of hepatocyte injury biomarkers, including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transfcrase (gamma-GT), cytokeratin (CK) 18-M30 and CK 18-M65 and plasma fibroblast growth factor 21 (FGF21). Changes in gamma-GT correlated with changes in liver PDFF (rho = 0.53, p = 0.02). Dapagliflozin alone and in combination with OM-3CA improved glucose control and reduced body weight and abdominal fat volumes. Fatty acid oxidative stress biomarkers were not affected by treatments. There were no new or unexpected adverse events compared with previous studies with these treatments. Conclusions/interpretation Combined treatment with dapagliflozin and OM-3CA significantly reduced liver fat content. Dapagliflozin monotherapy reduced all measured hepatocyte injury biomarkers and FGF21, suggesting a disease-modifying effect in NAFLD.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Dapagliflozin
- Docosahexaenoic acid
- Eicosapentaenoic acid
- Liver steatosis
- Non-alcoholic fatty liver
- growth-factor 21
- insulin sensitivity
- controlled-trial
- fish-oil
- steatohepatitis
- glucose
- oxidation
- pnpla3
- resistance
- adaptation
- Endocrinology & Metabolism
- Dapagliflozin
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Eriksson, Jan W.
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Lundkvist, Per
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Jansson, Per-And ...
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Johansson, L.
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Kvarnstrom, M.
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Moris, L.
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Miliotis, T.
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Forsberg, G. B.
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Risérus, Ulf, 19 ...
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Lind, Lars
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Oscarsson, J.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Diabetologia
- By the university
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University of Gothenburg
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Uppsala University