Common diabetic drug can trigger rare COVID complications

Diabetes patients on glucose-lowering drugs are at risk of rare COVID-19 complications, especially those who use a popular class of diabetes drugs called sodium-glucose cotransporter 2 inhibitors (SGLT2i), which function by releasing excess glucose in the urine.

In diabetes patients, rare but severe complications, like the potentially lethal condition diabetic ketoacidosis (DKA), can arise when illness or certain conditions prevent cells from receiving enough glucose to fuel their functioning.

The researchers at Brigham and Women's Hospital observed an uptick in a particular type of DKA called euDKA during the pandemic

EuDKA is a subset of the diabetes complication known as DKA, which occurs when the body's cells fail to absorb enough glucose and compensate by metabolizing fats instead, creating a build-up of acids called ketones.

EuDKA differs from DKA in that it is characterised by lower blood sugar levels, making it more difficult to diagnose.

Underlying nearly all euDKA cases is a state of starvation that can be triggered by illnesses that cause vomiting, diarrhea, and loss of appetite and can be compounded by the diuretic effect of SGLT2i drugs, noted the study published in The American Association of Clinical Endocrinologists Clinical Case Reports.

"We have the background knowledge of recognising that SGLT2 inhibitors can cause DKA and euDKA," said corresponding author Naomi Fisher of the Division of Endocrinology, Diabetes, and Hypertension.

"Our report reinforces that if patients are ill or have loss of appetite or are fasting, they should pause their medication and not resume until they are well and eating properly."

Brigham researchers studied five unusual euDKA cases brought to the diabetes inpatient services within the span of two months, three of which occurred in one week, at the height of the pandemic in Boston in the spring of 2020.

The authors also suspect that Covid-19 may particularly exacerbate euDKA risks.

When the virus infects a patient, it binds to cells on the pancreas that produce insulin and may exert a toxic effect on them.

Studies of the earlier SARS-CoV-1 virus found that many infected patients had increased blood sugar.

"It's been posited through other models that the virus may be preferentially destroying insulin-producing cells," Fisher said.

The authors encourage patients and physicians to halt SGLT2i-use in the event of illness, which is already standard practice for the most common diabetes drug, metformin.