mAb glucagon receptor blocker suitable for further development

August 4, 2017

(HealthDay)—The glucagon receptor blocker REGN1193, a fully human monoclonal antibody, seems safe and tolerable enough for further development, according to a study published online July 28 in Diabetes, Obesity and Metabolism.

Ana Kostic, Ph.D., from Regeneron Pharmaceuticals in Tarrytown, N.Y., and colleagues gave healthy men and women single ascending doses of REGN1193 ranging from 0.05 mg/kg to 0.6 mg/kg (42 participants) or placebo (14 participants) intravenously. Over 106 days, the authors assessed safety, tolerability, and pharmacokinetics.

The researchers found that REGN1193 was well tolerated overall, with small and transient dose-dependent increases in hepatic aminotransferases. There was no increase in . Across all dose groups, 43 percent of participants on placebo and 57 percent on REGN1193 had hypoglycemia; all episodes of hypoglycemia were asymptomatic, >50 mg/dL, and no treatment or medical assistance was needed. REGN1193 inhibited the glucose increase stimulated by in a dose-dependent manner. The glucagon-induced glucose area under the curve at 0 to 90 minutes was inhibited by the 0.6 mg/kg dose by 80 to 90 percent on days three and 15, while blunting the C-peptide increase. There were independent dose-dependent increases in total glucagon-like peptide 1 (GLP-1), GLP-2, and glucagon with REGN1193, with plasma levels returning to baseline by day 29 in all dose groups.

"The occurrence of transient elevations in serum hepatic aminotransferases observed here and reported with several small molecule antagonists suggest an on-target effect of glucagon receptor blockade," the authors write.

Several authors disclosed financial ties to the pharmaceutical industry, including Regeneron, which is developing REGN1193 and funded the study.

Explore further: Similar defects ID'd for T2DM, chronic pancreatitis and diabetes

More information: Abstract
Full Text

Related Stories

Similar defects ID'd for T2DM, chronic pancreatitis and diabetes

August 2, 2017
(HealthDay)—Patients with type 2 diabetes and those with diabetes secondary to chronic pancreatitis have similarly impaired α-cell responses to oral glucose ingestion and hypoglycemia, according to a study published online ...

G-pen may aid hypoglycemia with type 1 diabetes

February 22, 2016
(HealthDay)—Mini-dose glucagon administered using a stable, ready-to-use G-Pen Mini glucagon may be an effective option for mild to moderate hypoglycemia in adults with type 1 diabetes, according to a study published online ...

Low-carb diet cuts tx effect of glucagon in hypoglycemia

November 7, 2016
(HealthDay)—For patients with type 1 diabetes, a low-carbohydrate diet (LCD) results in lower incremental rises in plasma glucose (PG) after mild hypoglycemia compared with an isocaloric high-carbohydrate diet (HCD), according ...

Glucagon receptor antagonist ups blood pressure in T2DM

February 23, 2017
(HealthDay)—For patients with type 2 diabetes, once-daily treatment with the glucagon receptor antagonist LY2409021 is associated with increases in ambulatory blood pressure (BP), according to a study published online Feb. ...

Glucagon, GLP-1 co-infusion can reduce appetite

June 25, 2014
(HealthDay)—Co-infusion of glucagon and glucagon-like peptide 1 (GLP-1) correlates with a reduction in appetite, and GLP-1 protects against glucagon-induced hyperglycemia in healthy volunteers, according to a study published ...

GI adverse events up with GLP-1 receptor agonists

November 16, 2016
(HealthDay)—Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are associated with increased risk of gastrointestinal adverse events (AEs), with risk varying based on dose, background medications, and type of GLP-1 ...

Recommended for you

Personalized blood sugar goals can save diabetes patients thousands

December 11, 2017
A cost analysis by researchers at the University of Chicago Medicine shows treatment plans that set individualized blood sugar goals for diabetes patients, tailored to their age and health history, can save $13,546 in health ...

Kidney disease increases risk of diabetes, study shows

December 11, 2017
Diabetes is known to increase a person's risk of kidney disease. Now, a new study from Washington University School of Medicine in St. Louis suggests that the converse also is true: Kidney dysfunction increases the risk of ...

Type 2 diabetes is not for life

December 5, 2017
Almost half of the patients with Type 2 diabetes supported by their GPs on a weight loss programme were able to reverse their diabetes in a year, a study has found.

Skipping breakfast disrupts 'clock genes' that regulate body weight

November 30, 2017
Irregular eating habits such as skipping breakfast are often associated with obesity, type 2 diabetes, hypertension and cardiovascular disease, but the precise impact of meal times on the body's internal clock has been less ...

Type 2 diabetes has hepatic origins

November 28, 2017
Affecting as many as 650 million people worldwide, obesity has become one of the most serious global health issues. Among its detrimental effects, it increases the risk of developing metabolic conditions, and primarily type ...

Critical link between obesity and diabetes has been identified

November 28, 2017
UT Southwestern researchers have identified a major mechanism by which obesity causes type 2 diabetes, which is a common complication of being overweight that afflicts more than 30 million Americans and over 400 million ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.