SGLT2 inhibitors (sodium-glucose cotransporter-2 inhibitors, SGLT2i, such as canagliflozin) can lead to elevated ketone bodies and even diabetic ketoacidosis. This review discusses the mechanisms behind this phenomenon.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012260/
SGLT2i in the kidney enhance glucose excretion and cause the reabsorption of ketone bodies. In the pancreas, it is thought that SGLT2i inhibit beta cells, causing increased lipolysis, adding to the pool of ketone bodies [16-18]. They have also been found to stimulate alpha cells of the pancreas, inducing the release of glucagon and causing an imbalance in glucagon/insulin levels [18,19].
Inspired by this passage, perhaps diabetes patients inherently need elevated blood glucose levels. Originally, 5 mmol/L could meet the demand, but as the patients’ glucose utilization decreases, now 10 mmol/L is needed.
When using SGLT2i, blood glucose is rapidly lowered to what appears to be a normal 5 mmol/L, but the energy provided by this blood glucose is insufficient for the patient’s metabolism. Therefore, more energy must be supplied by increasing lipolysis and the secretion of glucagon (which raises blood glucose).