medwireNews: Experts have developed consensus recommendations for minimizing diabetic ketoacidosis (DKA) risk in patients with type 1 diabetes treated with sodium-glucose cotransporter (SGLT) inhibitors.
These agents are increasingly being used off-label in type 1 diabetes management, and several SGLT inhibitors are “currently under review by US Food and Drug Administration (FDA) and European regulatory agencies as an adjunct to insulin therapy in people with type 1 diabetes,” say Christopher Parkin (CGParkin Communications, Inc., Boulder City, Nevada, USA) and co-authors.
They explain that recent studies have demonstrated an increase in absolute DKA risk with SGLT inhibitor treatment, sometimes in patients with near-normal blood glucose levels, thus “complicating the recognition/diagnosis of DKA and potentially delaying treatment.”
As reported in Diabetes Care, the international panel of 26 clinicians and researchers developed their guidance based on evidence from randomized trials and their clinical experience.
The recommendations stress that selecting appropriate patients for SGLT inhibitor therapy is “critical” for attenuating DKA risk. Parkin and colleagues say that the “paramount criterion for patient selection” is normal ketone levels, defined as blood concentration below 0.6 mmol/L and negative urinary ketones, but individual patient factors, such as ability to follow ketone monitoring regimens, must also be taken into account.
They specify that SGLT inhibitors should not be given to pregnant women with type 1 diabetes or patients using low-carbohydrate or ketogenic diets, and point out that those using an insulin pump are at increased DKA risk due to the possibility of malfunction.
“It should be noted that treatment with SGLT-inhibitors in patients using insulin pumps with automated features including low glucose insulin suspend and hybrid closed loop has not been well studied,” remark the authors.
Parkin and colleagues recommend that “insulin must be reduced cautiously” when initiating SGLT inhibitors, and that the starting dose of the SGLT inhibitor should be as low as possible. After initiating an SGLT inhibitor, they advocate ketone testing via routine patient self-monitoring of beta-hydroxybutyrate, with retesting of glucose and ketone levels every 1–3 hours in those with elevated ketones.
The experts outline a number of situations in which SGLT inhibitors should be discontinued, including when patients experience nausea, vomiting, or abdominal discomfort, and during hospitalization. When patients are switching the type of insulin therapy – for example from injections to a pump – SGLT inhibitors should be discontinued until insulin doses are adjusted and ketone levels are normal.
The team emphasizes that patient and clinician education is key to mitigating DKA risk. They underline that “[a]ll patients should receive thorough instruction in DKA risk factors, ketone monitoring and treatment protocols,” and that emergency departments should be “made aware that DKA can present without overtly elevated glucose levels in patients treated with SGLT-inhibitors.”
Together, these recommendations should “provide a starting point for the safe use of SGLT-inhibitor therapy in this population,” write the authors.
They continue: “Because much of the evidence for DKA risk has been garnered from randomized clinical trials with highly-selected patients, additional research is needed to evaluate the efficacy and DKA risk of SGLT-inhibitors in larger cohorts of type 1 diabetes patients, using real-world methodologies.”
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