Response evaluation of SGLT2 inhibitor therapy in patients with type 2 diabetes mellitus using 18F-FDG PET/MRI

Introduction Inhibitors of sodium-glucose linked transporter-2 (SGLT2i) are enhancing glucose excretion in the proximal renal tubules, and thus are increasingly used to lower blood glucose levels in patients with type 2 diabetes mellitus (T2DM). The glucose analog 2-deoxy-2-(F-18) fluoro-D-glucose (FDG) can be used to quantify renal function in vivo, and due to an affinity for SGLT2 could also provide information about SGLT2 transporter function. Our objectives in this study were, therefore, to assess the impact of SGLT2i on renal function parameters in patients with T2DM and identify predictive parameters of long-term response to SGLT2i using dynamic FDG positron emission tomography (PET)/MRI. Methods PET FDG renal function measures such as mean transit time (MTT) and general renal performance (GRP) together with glomerular filtration rate (GFR) were determined in 20 patients with T2DM before (T2DM(baseline)) and 2 weeks after initiation of therapy with SGLT2i (T2DM(SGLT2i)). Additionally, dynamic FDG PET data of 24 healthy subjects were used as controls. Results MTT in T2DM(baseline) was significantly higher than in healthy controls (5.7min vs 4.3min, p=0.012) and significantly decreased to 4.4min in T2DM(SGLT2i) (p=0.004). GRP of T2DM(SGLT2i) was higher than of T2DM(baseline) (5.2 vs 4.7, p=0.02) and higher but not significantly than of healthy individuals (5.2 vs 5.1, p=0.34). Expectedly, GFR of healthy participants was significantly higher than of T2DM(baseline) and T2DM(SGLT2i) (122 vs 92 and 86mL/min/1.73m(2), respectively; p<0.001). The higher the GRP value in kidneys of T2DM(SGLT2i), the lower was the glycated hemoglobin level 3 months after therapy initiation. Conclusion MTT and GRP values of patients with T2DM shifted significantly toward values of healthy control 2weeks after therapy with SGLT2i begins. GRP in T2DM(SGLT2i) was associated with better long-term glycemic response 3months after initiation of therapy. Trial registration number NCT03557138.