Study Identifies Risk Groups for Ketoacidosis, a Severe Side Effect of SGLT2 Inhibitors
核心洞察
A Scandinavian registry study of more than 280,000 type 2 diabetes (搜索) patients found that SGLT2 inhibitors (搜索) carry a persistent risk of ketoacidosis (搜索), not just during early treatment.
Patients with prior ketoacidosis (搜索), high blood glucose, low body weight, malnutrition, or a history of hypoglycaemia faced the highest risk of the rare but potentially life-threatening condition.
Infection was the most common triggering or co-occurring event, while kidney impairment, stroke, and major surgery were also more frequent among affected patients.
A new study published in The Lancet Diabetes & Endocrinology has identified the patient groups most at risk of ketoacidosis (搜索), a rare but potentially life-threatening side effect of SGLT2 inhibitors (搜索), a widely used class of medicines for type 2 diabetes (搜索). Drawing on national health registry data from Sweden, Denmark and Norway, researchers analysed more than 280,000 patients with type 2 diabetes treated with SGLT2 inhibitors to determine how often ketoacidosis occurred and which factors were associated with an increased risk.
SGLT2 inhibitors (搜索) lower blood sugar by increasing the amount of sugar released by the kidneys via urine. Beyond glucose control, the medicines can reduce the risk of heart and kidney disease and have been shown to aid weight loss. However, they are also associated with an increased risk of ketoacidosis (搜索), a condition in which a lack of insulin causes the body to produce large amounts of ketones, disrupting the body's acid–base balance and, in the worst cases, becoming life-threatening.
Risk Factors Identified
The results showed that the risk was particularly high among patients who had previously experienced ketoacidosis (搜索), had high blood glucose levels, low body weight, or signs of malnutrition. Previous episodes of hypoglycaemia were also associated with an increased risk. Around 10 per cent of people with type 2 diabetes (搜索) have a body mass index that is not in the overweight or obesity category, according to charity Diabetes UK, underscoring the relevance of the low-body-weight finding.
Experts have previously suggested that the drugs encourage the body to burn fat for energy, which fuels the release of ketones.
Triggers and Co-Occurring Events
The researchers found that infection was the most common triggering or co-occurring event in cases of ketoacidosis (搜索). Other acute conditions, such as kidney impairment, stroke and major surgery, were also more common among affected patients.
A Persistent, Not Just Early, Risk
Previous studies have mainly examined the risk during the initial stages of treatment. The new study shows that although the risk is highest during the first few months, it remains elevated throughout the period in which the patient is taking the medication.
"SGLT2 inhibitors (搜索) provide medical benefits for many patients," said Peter Ueda, assistant professor at the Department of Medicine in the Karolinska Institute (搜索). "Our findings are not primarily about avoiding treatment, but about improving our ability to identify high-risk patients and use these medicines more safely."
The researchers also hope the findings will help doctors decide when treatment should be stopped, and they plan to study their findings in more detail and investigate other rare but serious side effects of modern diabetes medicines.
Clinical Context
The warning follows separate research showing that deaths from ketoacidosis (搜索) are on the rise in the UK. Last year, researchers from Imperial College London found ketoacidosis cases rose by 81 per cent between 2015 and 2023. SGLT2 inhibitors (搜索) are prescribed to around a third of the UK's type 2 diabetics, and four types are available in the UK as once-daily tablets: dapagliflozin (Forxiga), canagliflozin (Invokana), empagliflozin (Jardiance), and ertugliflozin (Steglatro).
Symptoms of ketoacidosis (搜索) can include feeling thirsty and needing to urinate more often than usual, as well as stomach pain, nausea or vomiting, diarrhoea and blurry vision. Other warning signs include unusually deep breathing, fruity-smelling breath and feeling extremely tired, sleepy or confused.