Avexitide (Eiger Biopharmaceuticals), a first-in-class GLP receptor blocker, has significantly reduced hypoglycemia in patients with refractory post-obesity hypoglycemia, a new study found.
Post-obesity hypoglycemia is a complication of obesity surgery and is estimated to occur in approximately 29% to 34% of those undergoing Ruwai gastric bypass surgery and 11% to 23% of those undergoing vertical sleeve gastrectomy. It has been. It usually appears about 1 to 3 hours after eating and can cause severe neuroglycopenic symptoms such as blurred vision, confusion, drowsiness, and incoordination.
In addition, more than one-third (37%) of this condition is unaware of hypoglycemia. This can lead to about 59% seizures, 50% unconsciousness and hospitalization, car accidents and even death. More than 90% of people in this situation consider themselves disabled and 41% report that they cannot work.
There is currently no approved treatment for post-obesity hypoglycemia. Standard treatment is a medical nutrition therapy that includes a low-carbohydrate diet with carbohydrate restrictions and a small amount of frequent mixed diets. If this does not work, out-of-line stage medications such as acarbose, octreotide, and diazoxide are being tried.
However, “these are limited by efficacy and tolerability,” said Dr. Marilyntan, MD, who presented the results of a phase II trial of abextide on June 11 at ENDO 2022, the annual meeting of the Endocrine Society. I did.
In very severe cases, gastrostomy tubes or bypass reversals are optional, but they lead to weight recovery and incomplete effects. Tan, a clinical associate professor of endocrinology at Stanford University School of Medicine in Stanford, California, said:
Pathophysiology is not fully understood, but there appears to be an exaggerated GLP-1 response leading to abnormal insulin secretion and symptomatic hyperinsulinemia hypoglycemia. She explained that abexitide (formerly exendin 9-39) blocks the GLP-1 receptor and alleviates the excessive GLP-1 response.
Session moderator Michel Van Name, MD, was asked to comment. Medscape Medical News“This is a problem, and it is important to understand it better and identify different treatment options so that these patients can continue to live a complete and healthy life after obesity surgery.”
Avexitide also has the potential to treat congenital hyperinsulinosis. This is “a very difficult disease to treat for babies,” said Vanname, a pediatric endocrinologist at Yale University in New Haven, Connecticut.
The drug reduced all levels of hypoglycemia beyond the type of surgery
The study enrolled 14 women and 2 men with post-surgery hypoglycemia of severe refractory obesity despite medical nutritional therapy. The majority (9) underwent Ruwai gastric bypass surgery, 4 underwent vertical sleeve gastrectomy, 2 underwent gastrectomy, and 1 underwent Nissen fundoplication. Seven patients (43.7%) experienced unconsciousness due to hyperinsulinemia hypoglycemia. No one was diabetic.
They were randomly assigned 45 mg subcutaneously abexitide twice daily or 90 mg once daily for 14 days each and switched to other doses after a 2-day washout period.
Both doses resulted in a significant reduction in hypoglycemia, as measured by autologous blood glucose monitoring. Once-daily administration reduced level 1 hypoglycemia (glucose <70 mg / dL) by 67.5% and level 2 (<54 mg / dL) by 53.3% (<54 mg / dL).P = .0043).
Severe hypoglycemia (ie, changes in mental status / needing support) showed an even greater reduction — 67.5% (twice daily).P = .0003) and 66.1% at once-daily doses (= .0003)P = .0003).
“This is in line with what was seen in previous abexitide trials,” Tan said.
Blind continuous glycemic monitoring (CGM) was used to capture more hypoglycemic events because the patient picked up episodes that were unnoticed. The percentage of time spent on Level 1 and Level 2 hypoglycemia, and the absolute number of 14-day hypoglycemic events, was significantly reduced.
Here, the effect was greater with a once-daily 90 mg dose, reducing the time spent and the number of events by up to 65%, but the results of the twice-daily dose were also significant, Tan said. I am.
This drug was effective in all surgical subtypes. Patients who underwent vertical sleeve gastrectomy / gastrectomy had high baseline hypoglycemia and “had a strong response to subcutaneous injection of avextide, which confirms the important role of GLP-1. “I will.” Said Tan.
There were no serious adverse events. The most commonly reported adverse events were diarrhea, headache, bloating, and injection site reactions / bruises. Everything was mild and self-limiting and resolved without treatment. No participant withdrew from the study.
Eiger Biopharmaceuticals is currently designing Phase 3 trials in collaboration with the US Food and Drug Administration and the European Medicines Agency.
This study is an investor-led trial funded by Eiger Biopharmaceuticals. Tan is a site researcher with research support from Eiger Biopharmaceuticals, Inc. Van Name is the investigator for a clinical trial sponsored by Provention Bio.
Annual Meeting of the Endocrine Society # ENDO2022.
Announced on June 11, 2022.
Miriam E. Tucker is a freelance journalist based in the Washington, DC region. She is a regular contributor to Medscape, and her other works have been published in The Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She is on Twitter @MiriamETucker.
Follow us for news on diabetes and endocrinology twitter And on Facebook
..
