Excretion of glucose analogue with SGLT2 affinity predicts response effectiveness to sodium glucose transporter 2 inhibitors in patients with type 2 diabetes mellitus

Eur J Nucl Med Mol Imaging. 2023 Aug;50(10):3034-3041. doi: 10.1007/s00259-023-06256-7. Epub 2023 May 17.


Purpose: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) regulation, developed as treatment for patients with type 2 diabetes, can be imaged with the glucose analogue alpha-methyl-4-deoxy-4-[18F]fluoro-D-glucopyranoside (Me4FDG), a positron emission tomography (PET) tracer with a high affinity for SGLT1 and SGLT2 proteins. With regard to therapy effectiveness, we aimed to investigate whether clinical parameters or Me4FDG excretion could predict response to SGLT2i in patients with type 2 diabetes.

Methods: In a longitudinal, prospective study, 19 patients with type 2 diabetes underwent Me4FDG combined PET and magnetic resonance imaging (PET/MRI) scans at baseline and 2 weeks after initiation of therapy with SGLT2i, accompanied by the collection of blood and urine samples. Me4FDG-excretion was determined from the Me4FDG uptake in the bladder. Long-term response was determined by HbA1c level after 3 months; a strong response to the therapy was defined as a reduction of HbA1c by at least 10% from baseline.

Results: SGLT2i resulted in significantly increased Me4FDG excretion (4.8 vs. 45.0, P < 0.001) and urine glucose (56 vs. 2806 mg/dl, P < 0.001). Baseline urine glucose and baseline Me4FDG excretion correlated both with long-term decline in HbA1c with r = 0.55 (P < 0.05). However, only Me4FDG excretion was a predictor of a strong response to SGLT2i (P = 0.005, OR 1.9).

Conclusions: Using Me4FDG-PET, we demonstrated for the first time renal SGLT2-related excretion before and after short-term SGLT2i treatment. In contrary to other clinical parameters, SGLT2-related excretion before treatment was a robust predictor of long-term HbA1c response in patients with type 2 diabetes, suggesting that therapy effectiveness is only dependent of endogenous SGLT2 processes.

Keywords: Diabetes type 2; PET; SGLT2 inhibitors; Sodium glucose cotransporter 2; Therapy response.

MeSH terms

  • Diabetes Mellitus, Type 2* / diagnostic imaging
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucose / metabolism
  • Glycated Hemoglobin
  • Humans
  • Hypoglycemic Agents
  • Prospective Studies
  • Sodium-Glucose Transporter 2 / metabolism
  • Sodium-Glucose Transporter 2 / therapeutic use
  • Sodium-Glucose Transporter 2 Inhibitors* / pharmacology
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use


  • Sodium-Glucose Transporter 2 Inhibitors
  • Glycated Hemoglobin
  • Sodium-Glucose Transporter 2
  • Glucose
  • Hypoglycemic Agents