In regards to pharmacotherapy, patients with type 1 diabetes end up solely relying on insulin therapy for their diabetes management: what if there is an add on option in the form of SGLT inhibitors with insulin?
Sodium-Glucose Cotransporter (SGLT) inhibitors have shown positive improvements in patients with both type 1 and type 2 diabetes. Their off-label use as an adjunct with insulin therapy in patients with type 1 diabetes has increased due to their effects on A1C reduction, glycemic control, insulin dose reduction, and weight change. This is currently being investigated by the FDA. However, with the positives, there is also an increased risk for diabetic ketoacidosis (DKA). It is important to determine the right patient for this adjunct therapy by assessing their risks and properly educating them on how to monitor for DKA and how to treat if need be.
The authors reviewed previous studies and applied their knowledge to construct consensus recommendations for the safe use of SGLT inhibitors with insulin in patients with type 1 diabetes and to direct where future research should focus their efforts.
First, serum and urine ketones that were of concern were listed with what actions should be taken, depending on the levels. Probable DKA was listed as a serum ketone value > 54 mg/dL (> 3.0 mmol/L) presenting with hyperglycemia. It is important to note that patients can have an increased serum ketone value with normal or moderate elevated blood glucose levels < 250 mg/dL (13.9 mmol/L), termed euglycemic DKA (euDKA).
Preventing the development of DKA relies on knowing if your patient is a proper candidate for SGLT inhibitor therapy. It is important to assess risk factors, such as previous history and current ketone values, lifestyle, their ability to adhere to monitoring ketones and knowing remedial actions. Diet alone can put patients with type 1 diabetes at an increased risk, such as if they skip meals or eat a low-carbohydrate diet. Even things such as excessive alcohol can increase risk. In regards to insulin therapy, patients who use a pump, or patients who might miss a dose, are at an increased risk of developing DKA. The authors stated that SGLT inhibitors should not be used in patients with type 1 diabetes who are pregnant or < 18 years of age.
Once determined that a patient is a candidate for SGLT inhibitor adjunct therapy, with initiation, their insulin dose should be reduced. This is important to reduce the risk of DKA. Previous studies have shown that this reduction should be individualized for each patient but also for the SGLT inhibitor being initiated. Patients with a well-controlled A1C < 7.5%, did well with a 10-20% insulin dose reduction, versus those who were not well controlled, had a slight reduction, or none. It is important to monitor levels, and adjustments to carbohydrates may be made, again individualized based on the patient. Initially, adjustments in previous trials were made every 24-48 hours.
When initiating an SGLT inhibitor in a patient with type 1 diabetes, they should be started at the lowest dose possible, or split the lowest tablet. Based on their response, the dose should be adjusted, titrating slowly. In data from prior studies, lower doses still had reasonable efficacy with a lower risk of DKA.
As for monitoring, glucose monitoring won’t detect euDKA; thus, patients should use either a blood ketone meter, which is preferred, or urine testing. The frequency has not yet been determined and should be further explored but should be individualized from patient to patient. Patients should always test for ketones if they experience any symptoms of DKA. If the patient experiences nausea, vomiting or abdominal discomfort, they should discontinue the SGLT inhibitor and check for ketosis. If a patient tests and their ketone levels are elevated, they should discontinue therapy until their ketones return to baseline. Based on their value, the patient should be aware of whether they are to treat or to seek medical attention. If a value is elevated, it should be rechecked every 1-3 hours until resolution. Proper education on DKA risk factors, symptoms, levels, and treatment are all essential to decrease the risk of DKA.
Using SGLT inhibitors in patients with type 1 diabetes as an adjunct to their insulin therapies has shown positive benefits. However, with benefits come risks. It is important to analyze every possibility to help decrease the risk of your patient developing DKA. The authors believe future clinical trials are still needed to assess the dose-dependent effect of higher doses of SGLT inhibitors in an association with increased efficacy and increased DKA rates. Other future trials should investigate the efficacy in patients with extremely elevated A1C levels (> 10%). Another idea for future studies, the authors noted, is to develop an algorithm for reducing insulin doses properly. Lastly, trials should evaluate education programs and materials given to patients and clinicians for efficacy and usability.
- SGLT inhibitors are being used off-label in patients with type 1 diabetes due to their benefits seen in clinical trials.
- Patients with type 1 diabetes should be individually assessed for the initiation of SGLT inhibitor therapy as an add on to their therapy.
- Due to the risk of developing DKA, after proper assessment and before initiation, patients should be properly educated on their new medication, its risks, what symptoms to look out for, how to monitor, and what to do based on their measured values.
Danne, Thomas, et al. International Consensus on Risk Management of Diabetic Ketoacidosis in Patients With Type 1 Diabetes Treated With Sodium-Glucose Cotransporter (SGLT) Inhibitors. Diabetes Care. 2019 February 6.
Emma Kammerer, L|E|C|O|M Bradenton School of Pharmacy, PharmD Candidate