Sodium-glucose cotransporter-2 (SGLT2) inhibitors may soon be indicated for type 1 diabetes patients as adjunctive therapy to insulin. At least three SGLT inhibitors are moving toward Food and Drug Administration submission for type 1 diabetes, bringing with them the hope of improved glycemic control and decreased disease burden.
The latest developments in this evolving treatment area will be discussed during a symposium at the 78th Scientific Sessions titled SGLT Inhibition for Type 1 Diabetes Mellitus Management―How Far Have We Gone? The two-hour symposium will conclude the meeting on Tuesday, June 26, with no concurrent sessions scheduled to maximize attendance.
“This is a unique opportunity to review the whole scope of clinical development programs seeking regulatory approval for SGLT inhibitors in type 1 diabetes,” said Julio Rosenstock, MD, Director of the Dallas Diabetes Research Center at Medical City and Clinical Professor of Medicine at the University of Texas Southwestern Medical Center. “This symposium brings together the lead investigators from the three major competitors that are pursuing approval of a SGLT inhibitor for type 1 diabetes. They will report top-level data that will eventually be submitted to regulators.”
Dr. Rosenstock helped organize the symposium and he will present the latest data on empagliflozin from the EASE trial program. Attendees will also hear data on dapagliflozin from the DEPICT trial program presented by Paresh Dandona, MD, PhD, SUNY Distinguished Professor and Chief of Endocrinology at the University of Buffalo. John B. Buse, MD, PhD, Verne S. Caviness Distinguished Professor and Chief of Endocrinology at the North Carolina School of Medicine, will present data on sotagliflozin, a SGLT1 and 2 inhibitor, from the InTandem trial program.
“This symposium will level the playing field for the three agents, allowing attendees to get an entire clinical perspective so they can better gauge whether SGLT inhibition benefits outweigh the risks,” Dr. Rosenstock said. “They are probably going to see a fair consistency in the findings, with some differences in study design and perhaps different study populations. But all three presentations will likely show a positive impact on different facets of type 1 diabetes management that needs to be balanced with the potential risks and side effects.”
SGLT inhibitors, independent of insulin secretion or insulin action, consistently show clinically and statistically significant A1C lowering despite reductions in insulin doses when used as an adjunct therapy in type 1 diabetes, Dr. Rosenstock said. These glycosuric agents also show weight loss and consistent reductions in systolic blood pressure. This combination of benefits has led to increasing off-label use of SGLT inhibitors, which are approved for type 2 diabetes but not for patients with type 1 diabetes.
“Of course, there’s a tradeoff to SGLT inhibitors — there’s always a tradeoff for any pharmacologic-induced clinical benefit,” Dr. Rosenstock said. “In this case, it’s the small but relevant increased risk for developing diabetic ketoacidosis (DKA). What clinicians may need to realize is that DKA with SGLT inhibitors can be predictable, detectable, and preventable.”
This risk of DKA and the metabolic changes induced by SGLT inhibition on glucose, lipid, and ketone metabolism will be reviewed during the session by Ele Ferrannini, MD, Professor Medicine at the University of Pisa, Italy. He will discuss the metabolic processes that can lead to DKA, as well as practical tools to detect and treat the problem.
“If SGLT inhibitors are ever going to be approved for type 1 diabetes management, we have to have a proactive plan to mitigate the risk of DKA,” Dr. Rosenstock said. “Patients with type 1 diabetes should not be using these drugs without tools to monitor ketones in their blood so they can detect mild elevations of beta-OH-butyric levels early to promptly correct with insulin and adjustments to carbohydrate intake.”
The session’s final presenter, David Cherney, MD, PhD, Associate Professor of Medicine at the University of Toronto, will discuss diabetes kidney disease and cardiovascular risk in type 1 diabetes. He will present data that SGLT inhibition can slow the progression of kidney disease by modulating glomerulotubular balance, resulting in reductions of hyperfiltration.
“There’s also a strong case to be made for exploring the CV benefits of SGLT inhibition in type 1 diabetes to see if what has been demonstrated in type 2 diabetes can be replicated in type 1,” Dr. Rosenstock said. “We have come a long way in terms of better insulin formulations, better pumps, continuous glucose monitoring. People with type 1 diabetes are living longer and having fewer microvascular complications, but they are dying of cardiovascular disease three to four times more often than they would without diabetes. SGLT inhibition could make a huge difference. Long-term CV outcomes trials in type 1 diabetes are a reasonable next step, and hopefully Dr. Cherney will address it.”
Dr. Rosenstock said the symposium is a great reason to stay in Orlando through Tuesday morning. “I predict that the large room will overflow in attendance,” he said.