A1 Refereed original research article in a scientific journal
SGLT2 Inhibitor Dapagliflozin Increases Skeletal Muscle and Brain Fatty Acid Uptake in Individuals With Type 2 Diabetes : A Randomized Double-Blind Placebo-Controlled Positron Emission Tomography Study
Authors: Latva-Rasku, Aino; Rebelos, Eleni; Tuisku, Jouni; Aarnio, Richard; Bhowmik, Achol; Keskinen, Helmi; Laurila, Sanna; Lahesmaa-Hatting, Minna; Pekkarinen, Laura; Isackson, Henrik; Kirjavainen, Anna K.; Koffert, Jukka; Heurling, Kerstin; Nummenmaa, Lauri; Ferrannini, Ele; Oldgren, Jonas; Oscarsson, Jan; Nuutila, Pirjo
Publisher: American Diabetes Association
Publication year: 2024
Journal: Diabetes Care
Journal name in source: Diabetes care
Journal acronym: Diabetes Care
Volume: 47
Issue: 9
First page : 1630
Last page: 1637
ISSN: 0149-5992
eISSN: 1935-5548
DOI: https://doi.org/10.2337/dc24-0470(external)
Web address : https://doi.org/10.2337/dc24-0470(external)
Objective: The aim of this study was to investigate the impact of the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on tissue fatty acid (FA) uptake in the skeletal muscle, brain, small intestine, and subcutaneous and visceral adipose tissue of individuals with type 2 diabetes by using positron emission tomography (PET).
Research design and methods: In a 6-week randomized double-blind placebo-controlled trial, 53 patients with type 2 diabetes treated with metformin received either 10 mg dapagliflozin or placebo daily. Tissue FA uptake was quantified at baseline and end of treatment with PET and the long-chain FA analog radiotracer 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid. Treatment effects were assessed using ANCOVA, and the results are reported as least square means and 95% CIs for the difference between groups.
Results: A total of 38 patients (dapagliflozin n = 21; placebo n = 17) completed the study. After 6 weeks, skeletal muscle FA uptake was increased by dapagliflozin compared with placebo (1.0 [0.07, 2.0] μmol ⋅ 100 g-1 ⋅ min-1; P = 0.032), whereas uptake was not significantly changed in the small intestine or visceral or subcutaneous adipose tissue. Dapagliflozin treatment significantly increased whole-brain FA uptake (0.10 [0.02, 0.17] μmol ⋅ 100 g-1 ⋅ min-1; P = 0.01), an effect observed in both gray and white matter regions.
Conclusions: Six weeks of treatment with dapagliflozin increases skeletal muscle and brain FA uptake, partly driven by a rise in free FA availability. This finding is in accordance with previous indirect measurements showing enhanced FA metabolism in response to SGLT2 inhibition and extends the notion of a shift toward increased FA use to muscle and brain.
Funding information in the publication:
The study was funded by AstraZeneca AB (Gothenburg, Sweden). The work was also supported by a personal grant from the Finnish Medical Foundation (A.L.-R.)