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.

中文翻译：

---

SGLT2 抑制剂达格列净增加 2 型糖尿病患者的骨骼肌和脑脂肪酸摄取：一项随机双盲安慰剂控制的正电子发射断层扫描研究


目的 本研究的目的是探讨钠-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂达格列净对患有以下疾病的个体骨骼肌、大脑、小肠以及皮下和内脏脂肪组织中组织脂肪酸 (FA) 摄取的影响通过使用正电子发射断层扫描 (PET) 来诊断 2 型糖尿病。研究设计和方法 在一项为期 6 周的随机双盲安慰剂对照试验中，53 名接受二甲双胍治疗的 2 型糖尿病患者每天接受 10 mg 达格列净或安慰剂治疗。在基线和治疗结束时使用 PET 和长链 FA 类似物放射性示踪剂 14(R,S)-[18F]氟-6-硫杂-十七烷酸对组织 FA 摄取进行量化。使用 ANCOVA 评估治疗效果，结果以最小二乘均值和组间差异的 95% CI 报告。结果 共有 38 名患者（达格列净 n = 21；安慰剂 n = 17）完成了研究。 6周后，与安慰剂相比，达格列净增加了骨骼肌 FA 摄取（1.0 [0.07, 2.0] μmol ⋅ 100 g−1 ⋅ min−1；P = 0.032），而小肠或内脏的摄取没有显着变化或皮下脂肪组织。达格列净治疗显着增加全脑 FA 摄取（0.10 [0.02, 0.17] μmol ⋅ 100 g−1 ⋅ min−1；P = 0.01），在灰质和白质区域均观察到这种效应。结论 达格列净治疗六周可增加骨骼肌和大脑 FA 的摄取，部分原因是游离 FA 可用性的增加。这一发现与之前的间接测量结果一致，显示 FA 代谢因 SGLT2 抑制而增强，并扩展了向肌肉和大脑增加 FA 使用的转变的概念。