Results presented in the ADA 77th Scientific Sessions suggest the use of an investigational glucagon-blocking agent can improve glycemic levels and reduce insulin requirements.
A balance of insulin and glucagon are necessary for optimal blood glucose levels. However, patients with diabetes not only have a decrease in insulin, but an increase in glucagon levels as well. Glucagon will then stimulate gluconeogenesis and the breakdown of glycogen and fats to contribute to hyperglycemia. In theory, using a glucagon-blocking agent in patients with type 1 diabetes should reduce blood glucose levels and lower the insulin dose required to maintain target blood glucose concentrations. REMD-477, an investigational glucagon-blocking drug, is a monoclonal antibody that has been shown to normalize blood glucose levels in rodent studies without the need for exogenous insulin.
A phase 1 study was recently conducted to evaluate the effects of REMD-477 in patients with type 1 diabetes. The randomized, double-blind, placebo-controlled trial admitted a total of 21 patients for observation in an inpatient setting for a period of 5 days. Continuous glucose monitoring (CGM) data was gathered for approximately two weeks prior to the start of the study and the investigators maintained participant’s glucose levels by providing identical meals and continuous insulin infusions. On day 2, ten participants received a 70 mg subcutaneous REMD-477 injection while eleven participants received placebo injections. The study gathered data on the daily insulin use and glucose levels on days 3 and 4 as well as CGM data for approximately 8 weeks after administration of the study dose.
Results of the study indicated that on day 4, participants treated with REMD-477 reduced the amount of daily insulin use by 26% or 12 units compared to placebo (-14 vs 12; p = 0.02). The average daily blood glucose concentration was 20-31mg/dL lower in the REMD-477 treatment group compared to placebo (p < 0.05) in the first three weeks after the study dose. This can be contributed to the long half-life of the investigational drug (7-10 days). During the first week after the conclusion of the study, participants in the REMD-477 study group experienced more time in target glycemic range (71 vs 56; p = 0.001), less time in hyperglycemia (23 vs. 39; p = 0.001) and similar time in hypoglycemia (6 vs 5) compared to those in the placebo study group.
The results of this study show a single dose of REMD-477 can significantly reduce the daily insulin dose requirement, reduce time spent in hyperglycemia and increase the total time spent in target range without an increased risk of hypoglycemia in patients with type 1 diabetes. These qualities can help patients gain better control and management of their disease. These promising results of the phase 1 trial have launched a follow-up phase 2 trial to compare two different dose strengths of REMD-477 for an even longer trial period in an outpatient setting.
- Hyperglycemia in patients with type 1 diabetes is caused by an imbalance of insulin and glucagon.
- In this phase 1 study, a single dose of REMD-477 reduced the daily insulin dose requirement by 12 units on day 4 and increase time spent in target glucose concentration in patients with type 1 diabetes.
- REMD-477 will begin a phase 2 trial to gain better understanding on the effects of this investigational drug is multiple doses.
American Diabetes Association. Glucagon-Blocking Drug Reduces Need for Insulin and Improves Blood Glucose Levels for Patients with Type 1 Diabetes. Press Release. Available at: http://www.diabetes.org/newsroom/press-releases/2017/pettus-scientific-sessions-2017.html. Accessed June 21, 2017.
REMD Biotherapeutics. Results of Phase 1 Study presented in President’s Oral Session Presentation at the American Diabetes Association 77th Scientific Sessions. News. Available at: http://www.remdbio.com/new-media. Accessed June 21, 2017.
Joanna Martinez-Mendez, PharmD Candidate 2018, Lake Erie College of Osteopathic Medicine School of Pharmacy: FL Campus