Avexitide Promising for Hypoglycemia After Weight Loss Surgical procedure

Avexitide (Eiger Biopharmaceuticals), a first-in-class GLP-receptor blocker, considerably diminished hypoglycemia in sufferers with refractory post-bariatric hypoglycemia, new analysis finds.  

Submit-bariatric hypoglycemia is a complication of bariatric surgery that’s estimated to happen in about 29%-34% of people that bear Roux-en-Y gastric bypass and in 11%-23% of those that bear vertical sleeve gastrectomy. It usually manifests about 1-3 hours after meals and might result in extreme neuroglycopenic signs together with blurred imaginative and prescient, confusion, drowsiness, and incoordination.

As well as, a couple of third (37%) with the situation have hypoglycemic unawareness. This may result in seizures in about 59%, lack of consciousness and hospitalization in 50%, motorized vehicle accidents, and even dying. Greater than 90% with the situation take into account themselves disabled, and 41% report being unable to work.

There are not any at the moment accredited medical remedies for post-bariatric hypoglycemia. The usual of care is medical diet remedy involving a low carbohydrate weight loss plan with carb restriction and small, frequent combined meals. If this does not work, off-label stepped pharmacotherapy has been tried, together with acarbose (Precose), octreotide (Sandostatin), and diazoxide (Proglycem).

However “these are restricted by efficacy and tolerability,” mentioned Marilyn Tan, MD, who offered the findings from the part 2 trial of avexitide June 11 at ENDO 2022, the annual assembly of the Endocrine Society.

In very extreme circumstances, gastrostomy tubes or bypass reversal are choices however these result in weight regain and incomplete efficacy. “Protected, efficient, and focused therapies are wanted urgently for post-bariatric hypoglycemia,” mentioned Tan, scientific affiliate professor of endocrinology at Stanford College Faculty of Medication, Stanford, California.

The pathophysiology is not absolutely understood, however there seems to be an exaggerated GLP-1 response that results in irregular insulin secretion and symptomatic hyperinsulinemic hypoglycemia. Avexitide (previously exendin 9-39), blocks the GLP-1 receptor and mitigates the extreme GLP-1 response, she defined.

Requested to remark, session moderator Michelle Van Identify, MD, advised Medscape Medical Information, “This can be a drawback and it is vital for us to know extra about it and to establish completely different remedy choices so these sufferers can proceed to stay their full, wholesome lives post-bariatric surgical procedure.”

And, avexitide additionally holds potential for treating congenital hyperinsulinism, “which is a really difficult illness to deal with in infants,” famous Van Identify, a pediatric endocrinologist at Yale College, New Haven, Connecticut.

Drug Diminished All Ranges of Hypoglycemia, Throughout Surgical procedure Sorts

The examine enrolled 14 girls and a couple of males with extreme refractory post-bariatric surgical procedure hypoglycemia regardless of medical diet remedy. A majority (9) had undergone Roux-en-Y gastric bypass, 4 had vertical sleeve gastrectomy, 2 gastrectomy, and 1 had Nissen fundoplication. Seven sufferers (43.7%) had skilled lack of consciousness from hyperinsulinemic hypoglycemia. None had diabetes.

They have been randomly assigned to both subcutaneous 45 mg of avexitide twice every day or 90 mg as soon as every day for 14 days every, with a 2-day washout interval adopted by a change to the opposite dose.

Each doses resulted in vital reductions in hypoglycemia as measured by self-blood glucose monitoring. The once-daily dose diminished degree 1 hypoglycemia (glucose <70 mg/dL) by 67.5% and it diminished degree 2 (<54 mg/dL) by 53.3% (P = .0043).

Even larger reductions have been seen in extreme hypoglycemia (ie, altered psychological standing/requiring help) — by 67.5% for the twice-daily dose (P = .0003) and by 66.1% with the once-daily dose (P = .0003). 

“That is in keeping with what we have seen in prior avexitide trials,” Tan famous.

Extra hypoglycemic occasions have been captured utilizing blinded steady glucose monitoring (CGM), because it picked up episodes of which the affected person was unaware. There have been vital reductions in proportion time spent in degree 1 and degree 2 hypoglycemia, in addition to in absolute variety of hypoglycemic occasions over 14 days.

Right here, the impact was larger with the once-daily 90 mg dose, with reductions of as much as 65% in time spent, and variety of occasions, however outcomes for the twice-daily dose have been additionally vital, Tan mentioned.

The drug was efficient throughout all surgical subtypes. Sufferers who underwent vertical sleeve gastrectomy/gastrectomy had larger charges of hypoglycemia at baseline and “sturdy responses to avexitide subcutaneous injections. This helps the vital function of GLP-1,” Tan mentioned.

There have been no extreme hostile occasions. Essentially the most generally reported hostile occasions have been diarrhea, headache, bloating, and injection web site response/bruising. All have been gentle and self-limited and resolved with out remedy. No individuals withdrew from the examine.

Eiger Biopharmaceuticals is at the moment working with the US Meals and Drug Administration and the European Medicines Company to design a part 3 trial.

The examine is an investor-initiated trial with funding from Eiger Biopharmaceuticals. Tan receives analysis help from Eiger Biopharmaceuticals, Inc., as a web site investigator. Van Identify is an investigator for a trial sponsored by Provention Bio.

Annual Assembly of the Endocrine Society #ENDO2022.
Offered June 11, 2022.

Miriam E. Tucker is a contract journalist based mostly within the Washington DC space. She is a daily contributor to Medscape, with different work showing within the Washington Submit, NPR’s Photographs weblog, and Diabetes Forecast journal. She is on Twitter @MiriamETucker.

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https://www.medscape.com/viewarticle/975437