New research shows that Avexitide (Eiger Biopharmaceuticals), an innovative GLP-receptor-blocker, reduced hypoglycemia in patients suffering from refractory post-bariatric hyperglycemia.

Post-bariatric Hypoglycemia, a complication of bariatric surgeries, is a condition that can occur in approximately 29%-34% of patients who have undergone Roux-en Y gastric bypass surgery and 11%-23% in those who have undergone vertical sleeve gastrectomy. It usually manifests within 1-3 hours of eating and can cause severe neuroglycopenic symptoms such as blurred vision, confusion, and incoordination.

Another reason is that more than a third of those with the condition (37%) are hypoglycemic aware. This can cause seizures in 59% of patients, loss or hospitalization in 50%, motor vehicle accidents and even death. Over 90% of those with this condition report that they are disabled and 41% report that they cannot work.

Post-bariatric hypoglycemia is not currently treated with any approved medical treatment. Medical nutrition therapy is the standard of care. It involves a low-carbohydrate diet, carb restriction, and frequent small meals. Off-label stepped therapy has been used to treat patients who have failed this treatment. These include Precose (Precose), Sandostatin (Octreotide) and Proglycem (Diazoxide).

Marilyn Tan, MD, presented the results from the phase 2 trial with avexitide on June 11, at ENDO 2022. This annual meeting of Endocrine Society.

If the situation is very serious, bypass reversal or gastrostomy tubes may be an option. However, these options can lead to weight gain and ineffectiveness. Tan, clinical associate professor of Endocrinology at Stanford University School of Medicine in Stanford, California, stated that post-bariatric hypoglycemia requires urgent, safe, effective and targeted treatments.

Although the pathophysiology of this condition is still unclear, it appears that there is an exaggerated GLP-1 response which leads to hyperinsulinemic hypoglycemia and abnormal insulin secretion. She explained that Avexitide, formerly exendin 9-339, blocks the GLP-1 receptor to reduce the excessive GLP-1 response.

Michelle Van Name MD, the session moderator, said that when she was asked to comment, she stated, "This problem is real and we need to learn more about it so that these patients can continue living full and healthy lives after bariatric surgery."

Avexitide is also a potential treatment for congenital hyperinsulinism. Van Name, a Yale University pediatric endocrinologist, noted that this disease is very difficult to treat in babies.

The study included 14 women and 2 males with severe refractory hypoglycemia after bariatric surgery. Nine out of the ten patients had had Roux-enY gastric bypass. Four had vertical sleeve gastrectomy and two had gastrectomy. One had Nissen fundoplication. Seven patients (43.7%) had suffered from loss of consciousness due to hyperinsulinemic hypoglycemia. None had diabetes.

The participants were randomly assigned either 45 mg or 90 mg subcutaneously twice daily, for 14 days each. There was a 2-day washout period and then a switch to the next dose.

Both doses led to significant hypoglycemia reductions as determined by self-blood glucose monitoring. One-time daily dose decreased level 1 hypoglycemia (glucose >70 mg/dL by 67.5%) and level 2 (54 mg/dL by 53.3% (P =.0043).

Reduced blood sugar levels in severe hypoglycemia (i.e., those with altered mental status/requiring assistance) were even greater -- by 67.5% for twice-daily (P =.0003) and by 66.11% for once-daily (P =.0003).

Tan stated that this is consistent with previous avexitide trials.

Blinded continuous glucose monitoring, or CGM (continuous glucose monitoring blinded), captured more hypoglycemic episodes than the patient knew. There was a significant decrease in the time spent in levels 1 and 2 hypoglycemias, as well as in the absolute number of hypoglycemic episodes over 14 days.

Tan stated that the 90 mg once-daily dose had a greater effect, with a reduction of time and events of up to 65%. However, results with the twice-daily dose were significant.

All surgical types were affected by the drug's effectiveness. Patients who underwent vertical sleeve gastrectomy/gastrectomy had greater rates of hypoglycemia at baseline and "robust responses to avexitide subcutaneous injections. Tan stated that this supports GLP-1's critical role.

There were no serious adverse reactions. Most common adverse reactions were headaches, diarrhea, bloating, and reaction/bruising to injection sites. They were all mild, self-limiting and easily treated. The study was completed without withdrawals by any participant.

Eiger Biopharmaceuticals and the US Food and Drug Administration are currently working together to develop a phase 3 trial.

This is an investor-initiated study with funding from Eiger Biopharmaceuticals. Tan is a site investigator and receives research support by Eiger Biopharmaceuticals, Inc. Van Name is an investigator in a Provention Bio trial.

Annual Meeting of Endocrine Society #ENDO2022. June 11, 2022.

Miriam E. Tucker, a freelance journalist, is based in Washington DC. Her work has appeared in Medscape, NPR's Shots blog and Diabetes Forecast magazine. She is a regular contributor for Medscape. You can find her on Twitter at @MiriamETucker

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