Type 1 diabetes is a challenging disease to manage.

“Despite the emergence of revolutionary therapies for the treatment of type 2 diabetes, there is only one U.S. Food and Drug Administration (FDA)-approved non-insulin therapy for the treatment of type 1 diabetes: pramlintide, an injectable amylin analog that is used in conjunction with insulin. There are no FDA-approved oral therapies for the treatment of type 1 diabetes,” said Klara R. Klein, MD, PhD, Assistant Professor of Medicine at the University of North Carolina at Chapel Hill.

Dr. Klein will explore the role of glucokinase activators (GKAs) as an adjunctive therapy in type 1 diabetes at a symposium on Adjunctive Therapies to Prevent Complications in Type 1 Diabetes, on Monday, June 23, from 8:00–9:30 a.m., in Room W184 A–D of the McCormick Place Convention Center. She will be joined by Schafer Boeder, MD, Associate Clinical Professor of Medicine at the University of California, San Diego, who will discuss glucagon receptor antagonists (GRAs); Bruce A. Perkins, MD, MPH, FRCP(C), Professor of Medicine at the University of Toronto, Canada, who will highlight sodium-glucose-linked transporter (SGLT) inhibition; and Justin Gregory, MD, MSCI, Associate Professor of Pediatrics at Vanderbilt University, who will talk about incretins such as glucagon-like peptide-1 (GLP-1) and GLP-1/glucose-dependent insulinotropic peptide (GIP) dual agonists.

On-demand access to recorded presentations will be available to registered participants following the conclusion of the 85^th Scientific Sessions, from June 25–August 25.

While adjunctive therapy in type 1 diabetes has long been an area of interest in the field, there has been more research focus and progress on this topic recently. Many people with type 1 diabetes continue to have unmet needs and are unable to achieve and maintain glycemic targets, even with the use of newer insulins, continuous glucose monitoring, and automated insulin delivery systems.

“In addition to improving glycemic control, we need to address acute complications, such as severe hypoglycemia and diabetic ketoacidosis (DKA), which lead to emergency room visits, hospitalizations, and illness/death,” Dr. Boeder said. “Finally, people with type 1 diabetes have a much higher risk for cardiovascular disease, above and beyond what we would expect based on traditional risk factors.”

In her presentation, Dr. Klein will review data for cadisegliatin, an oral GKA being developed for the treatment of type 1 diabetes. GKAs not only improve hyperglycemia, but early evidence suggests that they can also prevent hypoglycemia.

“For people living with type 1 diabetes, the risk of hypoglycemia is a persistent concern,” Dr. Klein noted. “An adjunctive therapy that enables tighter glycemic control without increasing hypoglycemia risk would be a major advance. Additionally, a significant limitation with the use of adjunctive therapies, especially sodium-glucose cotransporter-2 (SGLT2) inhibitors, is the risk of DKA. It is encouraging that mechanistic studies suggest that GKAs do not exacerbate DKA risk.”

Dr. Boeder will discuss volagidemab, a first-in-class, fully humanized monoclonal antibody that competitively blocks glucagon binding at the receptor.

“Thus far, volagidemab, as adjunctive therapy with insulin, improves glycemic control without increasing hypoglycemia, while also lowering insulin dosing requirements,” he said. “This GRA has other intriguing potential metabolic effects, including slowing ketone formation, which may theoretically protect against DKA. It may also make the body more sensitive to insulin, which could have important downstream implications, such as in improving cardiovascular health.”

Dr. Boeder noted the sea change in type 2 diabetes management, enabled by integrating approaches, goes beyond glycemic management to target metabolic risk factors like cardiovascular disease, overweight/obesity, and kidney disease, to help patients live longer healthier lives. Such multidrug, multi-risk-directed strategies have not yet been adopted in type 1 diabetes, partly because the tools are lacking.

“There are great opportunities with the drugs that are currently being developed. With a bigger toolbox of approved therapies for the treatment of type 1 diabetes, we could not only improve hard outcomes, like glycemic control and cardiovascular outcomes, but also empower people to manage their diabetes more easily, improving their quality of life and peace of mind,” Dr. Klein said.