The Ketogenic Effect of SGLT-2 Inhibitors—Beneficial or Harmful?

Sodium–glucose cotransporter-2 (SGLT-2) inhibitors, also called gliflozins or flozins, are a class of drugs that have been increasingly used in the management of type 2 diabetes mellitus (T2DM) due to their glucose-lowering, cardiovascular (CV), and renal positive effects. However, recent studies suggest that SGLT-2 inhibitors might also have a ketogenic effect, increasing ketone body production. While this can be beneficial for some patients, it may also result in several potential unfavorable effects, such as decreased bone mineral density, infections, and ketoacidosis, among others. Due to the intricate and multifaceted impact caused by SGLT-2 inhibitors, this initially anti-diabetic class of medications has been effectively used to treat both patients with chronic kidney disease (CKD) and those with heart failure (HF). Additionally, their therapeutic potential appears to extend beyond the currently investigated conditions. The objective of this review article is to present a thorough summary of the latest research on the mechanism of action of SGLT-2 inhibitors, their ketogenesis, and their potential synergy with the ketogenic diet for managing diabetes. The article particularly discusses the benefits and risks of combining SGLT-2 inhibitors with the ketogenic diet and their clinical applications and compares them with other anti-diabetic agents in terms of ketogenic effects. It also explores future directions regarding the ketogenic effects of SGLT-2 inhibitors.