SGLT2 Inhibitors Increase the Risk of Diabetic Ketoacidosis Developing in the Community and During Hospital Admission

Sodium–glucose cotransporter type 2 inhibitors: managing the small but critical risk of diabetic ketoacidosis

“…We are aware of several local cases in which well patients underwent colonoscopy preparation, withheld their SGLT2 inhibitors for 3 days as instructed, but were then cancelled on the day of the planned procedure because their blood ketones were just above 1.5 mmol/L (with normal plasma bicarbonate and normal plasma glucose). While our study showed no cases of DKA associated with colonoscopy, gastroscopy or coronary angiography, a TGA enquiry revealed that four of 319 SGLT2 inhibitor‐associated DKA reports were linked to colonoscopy in patients with type 2 diabetes . None were associated with gastroscopy or coronary angiography.…”

“…In patients with type 2 diabetes, SGLT2 inhibitor users have a 50–100% increase in relative risk of DKA . In our recent study, the absolute risk of DKA was small, being 1.02 per 1000 (95% CI, 0.74–1.41 per 1000) in SGLT2 inhibitor users versus 0.69 per 1000 (95% CI, 0.58–0.82 per 1000) in non‐SGLT2 inhibitor users (odds ratio [OR], 1.48; 95% CI, 1.02–2.15; P = 0.037) over a 26‐month period . However, the risk of developing DKA as an inpatient was significantly higher in SGLT2 inhibitor users than in non‐users (OR, 37.4; 95% CI, 8.0–175.9; P < 0.0001) .…”

“…In our recent study, the absolute risk of DKA was small, being 1.02 per 1000 (95% CI, 0.74–1.41 per 1000) in SGLT2 inhibitor users versus 0.69 per 1000 (95% CI, 0.58–0.82 per 1000) in non‐SGLT2 inhibitor users (odds ratio [OR], 1.48; 95% CI, 1.02–2.15; P = 0.037) over a 26‐month period . However, the risk of developing DKA as an inpatient was significantly higher in SGLT2 inhibitor users than in non‐users (OR, 37.4; 95% CI, 8.0–175.9; P < 0.0001) . Notably, blood glucose levels may be normal or only slightly elevated in SGLT2 inhibitor‐associated DKA, giving rise to the term “euglycaemic DKA”, which may lead to delays in diagnosis and treatment.…”

Advances in type 2 diabetes therapy: a focus on cardiovascular and renal outcomes

“…In the most recent DECLARE‐TIMI 58 trial, diabetic ketoacidosis was uncommon, but occurred at a higher rate in the dapagliflozin group than in the placebo group (0.3% v 0.1%; P = 0.02) . A recent Victorian study found an incidence of diabetic ketoacidosis of 1.02 per 1000 in SGLT2 inhibitor users compared with 0.69 per 1000 among non‐SGLT2 inhibitor users with type 2 diabetes (odds ratio, 1.48; 95% CI, 1.02–2.15) …”

“…15 A recent Victorian study found an incidence of diabetic ketoacidosis of 1.02 per 1000 in SGLT2 inhibitor users compared with 0.69 per 1000 among non-SGLT2 inhibitor users with type 2 diabetes (odds ratio, 1.48; 95% CI, 1.02-2.15). 21 Diabetic ketoacidosis may be difficult to diagnose due to the absence of substantial hyperglycaemia (euglycaemic diabetic ketoacidosis). The mechanism is not clearly understood, but the current hypotheses include reduced insulin production due to glycosuria; promotion of glucagon secretion by pancreatic αcells, which may express SGLT2; and reduction in renal ketone body clearance 22,23 (Box 4).…”