ADC 2019: Australian reports shed light on SGLT2-related DKA

Diabetic ketoacidosis risk in patients taking SGLT2 inhibitors goes beyond the perioperative period and is more often associated with acute illness and infection, according to case reports presented at the Australasian Diabetes Congress in Sydney.

A review of 21 cases of SGLT2 inhibitor-associated DKA at Blacktown Hospital, NSW, found that most cases were precipitated by infection (12) or acute cardiac illness (4), with only four cases occurring with perioperative use.

The review found that patients with DKA associated with SGLT2 inhibitor tended to have poorly controlled diabetes and moderate to severe rather than mild ketosis.

Another case series presented in a poster by clinicians from the Prince of Wales Hospital, Sydney, found that a series of 11 patients with SGLT2 inhibitor-associated DKA differed from 40 with typical (non-drug) DKA in being older, having a higher BMI,  lower plasma glucose levels (16.9 vs 28.3) and lower ketone levels (4.63 vs 6.01).

The lower ketone levels may suggest a difference in acid-base balance and bicarbonate handling, though there was no difference between groups in bicarbonate levels, the report authors noted.

“A proposed mechanism for this is that SGLT2 inhibitors may have an indirect inhibitory effect on the sodium hydrogen exchanger 3 (NHE3) at the proximal tubule, thereby reducing bicarbonate reabsorption, resulting in more severe acidosis.,” they wrote.

“Correction of ketoacidosis therefore may not mean that acid-base has been achieved.”

And in a separate case series published this week in the MJA, clinicians from the Austin Hospital, Melbourne, said they had seen ‘alarming’ growth in incidence of severe DKA with ten reports related to SGLT2 inhibitors in the hospital since 2016.

Most patients (75%) had a blood sugar level of 11 mmol/L or lower at presentation and only two of the 12 cases related to a perioperative setting, they noted.

Most cases of DKA were associated with underlying infection such as influenza and pneumonia, or by lack of oral intake, the report authors said.

“We remind clinicians that the precipitants for diabetic ketoacidosis extend beyond the perioperative period. We advise caution when patients are experiencing other contributing factors illustrated by our case series, including acute illness, reducing insulin doses, poor oral intake, severe dehydration and low carbohydrate diet.”

And in another poster presented at ADC, endocrinologists at Peninsula Health, Frankston Victoria cautioned that bariatric surgery may also be a high-risk event for delayed onset euglycaemic DKA in people taking SGLT2 inhibitors, with several cases of reported between one and six weeks post-operatively.

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