While not approved by the Food and Drug Administration for type 1 diabetes, off-label use of sodium-glucose co-transporter 2 (SGLT2) inhibitors continues to increase. Research has shown positive patient outcomes, including reductions in A1C, body weight, fasting glucose, blood pressure, and insulin dosages, along with improvements in quality of life. But research also has shown an increased risk of diabetic ketoacidosis (DKA).
A panel of experts will review the latest science on the benefits and risks of SGLT2 inhibitors during a two-hour symposium on the final day of the Scientific Sessions. The symposium, which begins at 10:15 a.m. in room W415C (Valencia Ballroom), is titled SGLT Inhibition for Type 1 Diabetes Mellitus Management—How Far Have We Gone?
Ele Ferrannini, MD, Professor of Internal Medicine and Associate Investigator of the CNR (National Research Council) Institute of Clinical Physiology, Pisa, Italy, will open the symposium with a review of the metabolic effects of SGLT inhibition in type 1 diabetes.
The development of DKA in patients undergoing SGLT2 treatment follows the primary mechanism of action and classic metabolic pathway that leads to DKA, Dr. Ferrannini said. That reduces the possibility that SGLT2 inhibitors have unpredictable, off-target effects, he said.
“The special feature of DKA in patients on treatment with SGLT2 inhibitors is that because of the glycosuria, the glucose levels may not be as high as they typically are in classic DKA,” Dr. Ferrannini said. “The FDA issued a warning, not so much to the effect that these episodes may occur in people on treatment with the SGLT inhibitor at a much higher frequency, but they may go unrecognized because of the glucose levels that would not be very high, as is the case in classic DKA, but only moderately elevated so that the development of the complication may go unnoticed to both the patient and the physician.”
Dr. Ferrannini said he has prescribed SGLT2 inhibitors, which have been approved for the treatment of type 2 diabetes, for some of his type 1 diabetes patients. Another presenter, John B. Buse, MD, PhD, Professor of Medicine, Chief of Endocrinology, and Director of the Diabetes Center at the University of North Carolina School of Medicine, has also prescribed SGLT2 inhibitors for some of his type 1 diabetes patients.
Dr. Buse will discuss a development program to support regulatory approval of sotagliflozin, a novel dual inhibitor of SGLT1 and SGLT2. Results reported last year from the inTandem3 trial (A Phase 3 Study to Evaluate the Safety of Sotagliflozin in Patients With Type 1 Diabetes Who Have Inadequate Glycemic Control With Insulin Therapy Alone) indicate that sotagliflozin provided a moderate but significant reduction in A1C, body weight, and blood pressure, along with small reductions in insulin dosages.
The inTandem3 results also showed an increased risk for DKA. Moving forward, Dr. Buse said researchers will work to find ways to minimize DKA risk to enhance the risk-benefit ratio of sotagliflozin.
“I think it’s a great class of drugs in this setting,” Dr. Buse said. “It’s just a matter of figuring out how to use it safely and finding the right patients. That’s the bottom line. It’s not the education, though that will be important. It’s not the doctors, though they will have a learning curve. It’s the right patient, motivated and careful in their management of their disease.”
David Cherney, MD, PhD, Associate Professor at the University of Toronto, Canada, will review the mechanisms for cardiovascular and renal protection in SGLT2 inhibitors and the reasons why those pathways are important in type 1 diabetes and type 2 diabetes.
“The mechanisms that are protective with SGLT2 inhibitors in type 2 diabetes are likely to be just as applicable to type 1 diabetes,” Dr. Cherney said. “So our challenge is to see whether those mechanisms translate into benefits over the long term, thereby reducing morbidity and mortality in people with type 1 diabetes.”
Also during the symposium, Paresh Dandona, MD, Distinguished Professor and Chief of Endocrinology at State University of New York, Buffalo, will discuss the clinical efficacy and safety of dapagliflozin in type 1 diabetes patients. Dapagliflozin is another SGLT2 inhibitor approved for type 2 diabetes. And Julio Rosenstock, MD, Director of the Dallas Diabetes Research Center, will discuss the SGLT2 inhibitor empagliflozin.