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The SGLT2 Inhibitor Dapagliflozin Reduces Liver Fat but Does Not Affect Tissue Insulin Sensitivity: A Randomized, Double-Blind, Placebo-Controlled Study With 8-Week Treatment in Type 2 Diabetes Patients.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
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2019 (engelsk)Inngår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 42, nr 5, s. 931-937Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

OBJECTIVE: The aim of this study was to investigate tissue-specific effects of dapagliflozin on insulin sensitivity and liver and body fat in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS: This randomized, double-blind, parallel group, placebo-controlled study recruited 32 patients with type 2 diabetes. Enrolled patients were to have HbA1c 6.5-10.5% (48-91 mmol/mol) and ≥3 months of stable treatment with metformin, dipeptidyl peptidase 4 inhibitor, or their combination. Patients were randomized 1:1 to receive 10 mg dapagliflozin or placebo daily for 8 weeks. Before and after the intervention, tissue insulin sensitivity was measured using [18F]-fluorodeoxyglucose and positron emission tomography during hyperinsulinemic-euglycemic clamp. Liver proton density fat fraction (PDFF) and adipose tissue volumes were assessed using MRI, and blood biomarkers were analyzed.

RESULTS: After 8 weeks, glycemic control was improved by dapagliflozin (placebo-corrected change in HbA1c -0.39%, P < 0.01), but whole-body glucose uptake was not increased (P = 0.90). Tissue-specific insulin-stimulated glucose uptake did not change in skeletal muscle, liver, myocardium, or white and brown adipose tissue, and endogenous glucose production remained unaffected. However, there were significant placebo-corrected decreases in liver PDFF (-3.74%, P < 0.01), liver volume (-0.10 L, P < 0.05), visceral adipose tissue volume (-0.35 L, P < 0.01), interleukin-6 (-1.87 pg/mL, P < 0.05), and N-terminal prohormone of brain natriuretic peptide (-96 ng/L, P = 0.03).

CONCLUSIONS: In this study, 8 weeks of treatment with dapagliflozin reduced liver PDFF and the volume of visceral adipose tissue in obese patients with type 2 diabetes. Although glycemic control was improved, no effect on tissue-level insulin sensitivity was observed.

sted, utgiver, år, opplag, sider
2019. Vol. 42, nr 5, s. 931-937
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Identifikatorer
URN: urn:nbn:se:uu:diva-382943DOI: 10.2337/dc18-1569ISI: 000465238900036PubMedID: 30885955OAI: oai:DiVA.org:uu-382943DiVA, id: diva2:1314045
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AstraZenecaTilgjengelig fra: 2019-05-07 Laget: 2019-05-07 Sist oppdatert: 2019-05-15bibliografisk kontrollert

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