Glucagon-blocking drug reduces insulin requirements

When people think of diabetes, they inevitably think of the hormone insulin, but at this year’s 77th ADA Scientific Sessions, one of the most exciting developments involved insulin’s “sister” hormone glucagon. Researchers from University of California San Diego released the results of a study showing the glucagon-blocking drug REMD-477 can lower the amount of insulin required by adults with type 1 diabetes. What’s more, the drug improves blood glucose levels without increasing hypoglycemia.

Why block glucagon?

Glucagon and insulin are hormones that work in tandem to regulate blood glucose levels. Glucagon induces the liver to convert stored glycogen into glucose and release it into the bloodstream. Thus, glucagon increases blood glucose levels. Insulin, on the other hand, allows glucose to enter and “feed” the body’s cells. Thus, insulin lowers the amount of glucose in the blood.

In a person without diabetes, the pancreas produces both glucagon and insulin. Alpha cells in the pancreas produce glucagon, and beta cells produce insulin. In a person with type 1 diabetes, the immune system attacks the pancreas’ beta cells so they no longer produce insulin. Their alpha cells, however, continue to produce glucagon. In fact, a PWD’s alpha cells may produce even more glucagon than non-T1D persons, so blood glucose levels would be higher even without eating. Dr. Jeremy Pettus, the study’s lead author, says, “Our study strongly supports the long-held theory that blocking glucagon may have a significant clinical impact on care for people with type 1 diabetes by improving glucose levels and lowering insulin doses”.

About the Study

Twenty-one adults with type 1 diabetes participated a double-blind, randomized, placebo-controlled study. Researchers first collected information on the participants’ insulin use and glucose levels via CGM. Then participants checked into a clinical research unit for a total of 5 days, receiving the same meals and continuous IV insulin infusion. On day two, 10 adults received an injection of REMD-77. The remaining 11 received a placebo injection. Researchers monitored the participants’ insulin use and glucose levels throughout. After the five-day inpatient period, researchers monitored participants for eight weeks.

Study Results

Researchers compared the participants’ insulin use and glucose levels between day one versus day four of the study. First of all, they found that daily insulin use was decreased by 26% in adults who received REMD-477 compared with adults who received the placebo (P = .02). In addition, after eight weeks post-treatment, the average daily glucose levels was 20 to 31 mg/dL lower in the adults who received REMD-477. Also, no episodes of severe hypoglycemia were noted. Dr. Pettus says, “”We expected that the drug [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 hypoglycemia events was a surprise.”

What’s next?

Dr. Pettus and his team are planning a follow-up study with more participants over a longer period of time. While the first study measured the effect of REMD-77 after a single injection, the follow-up study will involve weekly injections.

Read the ADA’s press release on the REMD-477 study

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