We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
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
- Abstract
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.
- Subjects
POSITRON emission tomography; DAPAGLIFLOZIN; TYPE 2 diabetes; END of treatment; SODIUM-glucose cotransporter 2 inhibitors; SKELETAL muscle
- Publication
Diabetes Care, 2024, Vol 47, Issue 9, p1630
- ISSN
0149-5992
- Publication type
Article
- DOI
10.2337/dc24-0470