Glucagon-blocking drug reduces need for insulin, improves blood glucose levels in T1D patients
A single dose of the human glucagon receptor (GCGR) antibody, REMD-477, reduces the amount of insulin necessary and significantly improves glycaemic control in individuals with type 1 diabetes (T1D), according to a study presented at the ADA 2017 in San Diego, California, US.
“[P]eople with [T1D] produce too much glucagon … Our study strongly supports the long-held theory that blocking glucagon may have a significant clinical impact on care for people with [T1D] by improving glucose levels and lowering insulin doses,” said Dr Jeremy Pettus from the University of California, San Diego, California, US.
In this double-blind study on 21 adults with T1D, patients were randomized to receive a single subcutaneous injection of REMD-477 (70 mg, n=10) or placebo injection (n=11) on day 2 of a 5-day, inpatient observation period. [ADA 2017, abstract 378-OR]
Glucose levels were measured using Continuous Glucose Monitoring prior to and 8 weeks after admission. Participants were given standardized meals and constant intravenous insulin infusion to help maintain glucose levels.
On day 4, REMD-477 administration resulted in a 26 percent (12 units) reduction in insulin levels vs placebo (p=0.02). “Exposure to this [GCGR] significantly reduced insulin requirements during inpatient stay,” said Pettus.
Furthermore, during the three weekly periods after inpatient evaluation, there was a significant improvement in blood sugar levels as the average daily glucose concentration in REMD-477-treated patients was 20–31 mg/dL lower than the placebo group (p<0.05), with less insulin use.
Pettus underlined that if the difference in blood sugar levels persisted, it would be equivalent to a HbA1C drop of about 1 percent, which translates to a substantial change in glucose profiles.
Outpatient glycaemic control evaluation during the second treatment week (days 6–12) showed a statistically significant increase in time-in-range in the REMD-477 vs placebo group (71 vs 56 percent).
Overall, these findings demonstrate that a single REMD-477 injection effectively reduced total daily insulin requirements while improving glucose control, with no episodes of severe hypoglycaemia, said the researchers.
“We expected that [REMD-477] would have an effect, yet the degree to which the drug reduced the need for insulin and improved patients’ blood sugar levels without increasing hypoglycaemia events was a surprise,” said Pettus.
As the study measured the glucagon-blocking effect after one injection only, Pettus indicated that a follow-up study has been initiated to evaluate long-term treatment using different dose strengths in order to determine the impact of REMD-477 on blood glucose levels, insulin use, and weight in an outpatient setting.