Energy balance and metabolic changes with sodium‐glucose co‐transporter 2 inhibition

Abstract

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are the latest addition to the class of oral glucose-lowering drugs. They have been rapidly adopted into clinical practice because of therapeutic advantages, including weight loss and reduction in blood pressure, in addition to glycaemic benefits and a low intrinsic risk of hypoglycaemia. Although there are extensive data on the clinical effects of SGLT2 inhibition, the metabolic effects of inhibiting renal glucose reabsorption have not been fully described. Recent studies have identified compensatory metabolic effects, such as an increase in endogenous glucose production, and have also shown an increase in glucagon secretion during SGLT2 inhibition. In addition, there is a discrepancy between the expected and observed weight loss found in clinical studies on SGLT2 inhibitors, probably as a result of changes in energy balance with this treatment approach. SGLT2 inhibition is likely to have intriguing effects on whole body metabolism which have not been fully elucidated, and which, if explained, might help optimize the use of this new class of medicines.

Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation

“…Rajeev et al 85 have reviewed possible explanations, such as a compensatory increase in food intake, but the mechanism is uncertain. Ferrannini et al 86 reported that patients in an empagliflozin trial lost only 38% of the weight loss predicted from the calories lost via glycosuria, and suggested that this was due to an increase in food intake.…”

Comparative study of the effects of ipragliflozin and sitagliptin on multiple metabolic variables in Japanese patients with type 2 diabetes: A multicentre, randomized, prospective, open‐label, active‐controlled study

“…These two relatively new antidiabetic agents, ipragliflozin and sitagliptin, have been widely used in Japan. The two agents are known to have multiple benefits other than glucose‐lowering effects (Appendix S1); however, there have been few head‐to‐head studies comparing the pleiotropic effects of SGLT2 inhibitors and DPP‐4 inhibitors. In the present study, we performed a prospective randomized controlled study to compare the efficacy and safety profiles of ipragliflozin and sitagliptin.…”

“…4 These two relatively new antidiabetic agents, ipragliflozin and sitagliptin, have been widely used in Japan. The two agents are known to have multiple benefits other than glucose-lowering effects (Appendix S1) [5][6][7][8] ; however, there have been few head-to-head studies comparing the pleiotropic effects of SGLT2 inhibitors and DPP-4 Y. Tsurutani and K. Nakai contributed equally to this work.…”

Spotlight on ertugliflozin and its potential in the treatment of type 2 diabetes: evidence to date

“…As mentioned earlier, SGLT2 inhibition promotes significant energy loss through glycosuria, which causes weight loss 53. This is evident within 4 weeks of treatment but continues for up to 102 weeks in the longer duration trials 54,55.…”