Sodium-glucose Cotransporter 2 Inhibitors and the Risk of Diabetic Ketoacidosis; from Pathophysiology to Clinical Practice

Abstract

SGLT-2 inhibitors certainly predispose to euDKA, but it is unclear if, as certain precipitating factors are usually recognized on the background, DKA would also occur in the absence of an SGLT-2 inhibitor. Further investigation is required in order to establish or not SGLT- 2 inhibitors as causative factors of euDKA.

Fracture risk in patients with type 2 diabetes aged ≥50 years related to HbA1c, acute complications, BMI and SGLT2i-use in the DPV registry

“…Another possible explanation could be, that one risk factor for DKA is alcohol abuse 31 , which was more frequent in the fracture group compared to the control group in the present study and was stated as a risk factor for fractures, especially for hip fractures in older men, in previous studies 32,33 . A third explanation might be the possible association between SGLT2i medication and DKA, that is currently discussed in the literature 34,35 . At least in female patients, these two parameters could play a role, as in women, medication with SGLT2i was related to higher fracture risk in the present study.…”

Molecular Mechanisms of SGLT2 Inhibitor on Cardiorenal Protection

“…A multicenter cohort study in patients with type 2 diabetes showed that SGLT-2 inhibitors were associated with an almost 3-fold increased risk for diabetic ketoacidosis (DKA), and the molecular-specific analyses suggest it as a classic effect. [ 160 , 161 ]. The pathogenesis of SGLT2i-associated ketonemia is distinct from traditional DKA.…”

Glucagon in type 1 diabetes patients receiving SGLT2 inhibitors: A Friend or Foe?

“…However, there is some safety concern associated with their use in diabetic patients 9,10 . Indeed, SGLT2i have been reported to increase the risk of euglycaemic ketoacidosis, a rare but serious life‐threatening complication, especially in patients with type 1 diabetes 9–11 . SGLT2i increase plasma glucagon levels and simultaneously reduce blood glucose and insulin levels in type 2 diabetes 10,12 .…”