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Glucagon receptor blockade may reduce insulin dose requirement in type 1 diabetes
SAN DIEGO — A single dose of an investigational agent that blocks glucagon receptors can lower the amount of insulin needed and improve glucose levels without increased hypoglycemia in adults with type 1 diabetes, according to a presenter here.
“In humans with type 1 diabetes, it is well-known that glucagon is dysregulated,” said Jeremy Pettus, MD, assistant professor of medicine in the department of endocrinology at the University of California, San Diego. “For multiple reasons, people with type 1 diabetes produce too much glucagon, which can increase sympathetic glucose output and make people have profound issues with hyperglycemia. The concept we were going to test is basically, can we use this concept that’s been proven in animal models in individuals with type 1 diabetes?”
Pettus and colleagues evaluated 21 adults (eight men) with type 1 diabetes randomly assigned to a single 70-mg subcutaneous injection of the glucagon-blocking drug REMD-477 (REMD Biotherapeutics; n = 10) or a placebo injection (n = 11) to determine the effect of the agent on total daily insulin required to maintain targeted glycemic control. Information on baseline insulin use was collected from continuous glucose monitoring systems, and participants were then admitted to a clinical research unit for 5 days; participants were given REMD-477 or placebo on the second day of admission.
Change in daily insulin requirements on day 4 from day 1 was the primary endpoint. Participants were provided with standard meals to ensure the same daily energy and macronutrient contents were consumed during the inpatient study. Post-absorptive plasma glucose level between 90 mg/dL and 120 mg/dL and postprandial plasma glucose less than 180 mg/dL were maintained by insulin through continuous subcutaneous infusion.
Daily insulin use was decreased by 26% with REMD-477 compared with placebo on day 4 (P = .02).
CGM systems were used to observe participants for 8 weeks. The REMD-477 group had 20 mg/dL to 31 mg/dL lower average daily glucose compared with the placebo group during the three weekly periods after inpatient observation (P < .05). The REMD-477 group also spent more time in target (70-180 mg/dL) compared with the placebo group during the observation period.
“Results of this study support the long-standing theory that blocking glucagon can have significant clinical impact in patients with type 1 diabetes in an area where there’s a very unmet need of other therapies to help people lower blood sugars and use less insulin,” Pettus said. “The glucagon receptor blockade with REMD-477 improved glycemic control and reduced insulin requirements in patients with type 1 diabetes as an inpatient, reducing their insulin requirements, reducing their average blood sugar, increasing their time-in-range. The next step is a 12-week multiple-dose study to evaluate the effects of REMD-477 on glycemic control and daily insulin use in patients with type 1 diabetes.” – by Amber Cox
Reference:
Pettus J, et al. 378-OR. Presented at: American Diabetes Association 77th Scientific Sessions; June 9-13, 2017; San Diego.
Disclosure : Pettus reports consulting for Dexcom, Insulet, MannKind, Novo Nordisk, Sanofi, Senseonics and Valeritas.