What to Expect Next in the GLP-1s Market

The overwhelming success of drugs like Ozempic and Wegovy has led pharmaceutical companies to develop new GLP-1 receptor agonists that target a wider range of conditions and reduce the frequency of injections.

Approximately one in eight American adults have ever used a medication that belongs to a class of drugs called glucagon-like peptide 1 receptor agonists (GLP-1RAs) intended for the treatment of type 2 diabetes and obesity, according to the KFF survey.

Both diabetes and obesity are worsening public health crises, with about 38.4 million Americans living with diabetes. Its prevalence is estimated to increase by 65% in the next 40 years, the Centers for Disease Control and Prevention data shows.

About 40% of adults in the United States have obesity, which is a risk factor not only for diabetes but also for hypertension, heart disease, and some cancers, among other conditions.

The GLP-1RAs work by mimicking the action of a hormone called GLP-1 released in the gut. The hormone stimulates insulin release, increases the feeling of satiety, and slows down the rate at which food is digested.

Dr. Sean Wharton, a medical director of the Wharton Medical Clinic, tells Healthnews that the currently available GLP-1RAs are a huge breakthrough in science and obesity medicine. However, they don’t solve all the aspects of weight loss management.

Cognitive behavioral therapy should be used by all individuals engaging in weight loss, according to Wharton. Despite weight loss, patients who start the drug with depression, or low positive mood, remain the same.

Pharmaceutical companies are working on addressing some of the limitations of existing GLP-1RAs. We spotted three patent applications that show promise in improving the drugs’ efficacy and administration.

A tri-receptor drug for a higher number of conditions

Eli Lilly and Company filed a patent application on August 15 for a tri-receptor agonist, a drug that provides the activity of three receptors: GLP-1, gastric inhibitory polypeptide (GIP), and glucagon.

GIP is released in the small intestine in response to food. It helps stimulate the production of insulin and increase sensitivity to it. Meanwhile, glucagon is a hormone produced in the pancreas that helps regulate blood sugar levels.

According to the patent application, the drug could help avoid unwanted side effects associated with too much activity of each receptor. It could be administered both orally and by injection, with the frequency ranging from once a day to once a week.

Due to a broader range of benefits than provided by GLP-1RAs alone, the new drug could be used to treat multiple conditions, including obesity, type 2 diabetes, non-alcoholic fatty liver disease, dyslipidemia, metabolic syndrome, osteoarthritis, and polycystic ovary syndrome.

In the phase 2 clinical trial testing retatrutide, a tri-receptor agonist, adults with obesity and overweight lost up to 17.5% on average within 24 weeks of the treatment. The participants also saw improvements in metabolic health measures such as blood pressure, cholesterol, and insulin.

An implantable device to reduce injection frequency

Treatment with GLP-1 receptor agonists may last months and years, requiring daily pills or multiple injections each month. Continuous dosage over time may reduce patient compliance, as individuals may forget to take medication or become tired of frequent injections.

According to a patent application filed on August 15, Celanese Corporation is developing a device that delivers one or more GLP-1 receptor agonists. This could be solved by implanting it.

The patent application suggests a cylindrical device between 1 and 60 mm long and 0.5 to 50 mm in diameter. It could be implanted into the skin, orally, rectally, or mucosally.

However, this is not the first attempt to create a GLP-1-releasing implant. Last year, the Food and Drug Administration’s committee of outside advisers turned down Intarcia’s six-month implant dosing exenatide, a type of GLP-1 RAs used for diabetes treatment.

Later this year, Vivani Medical will begin human trials of its six-month GLP-1 implant for chronic weight management in obese or overweight patients with a related comorbidity.

A double-receptor agonist to reduce side effects

Novo Nordisk filed a patent application for a drug that would combine the activity of GLP-1 and amylin receptor agonists. Amylin is a hormone co-secreted with insulin and is an important regulator of energy metabolism, delays gastric emptying, and suppresses appetite.

Thus far, only one product in the market contains amylin, sold under the brand name Symlin. It is intended to be used in patients with type 1 and type 2 diabetes.

The new drug is aimed at providing a similar level of activation of both GLP-1 and amylin receptor systems. This balance may allow activating both systems without side effects outweighing benefits, according to a patent application.

The GLP-1 and amylin receptor agonists could be taken orally every 12 to 60 hours.

Besides diabetes and obesity, the drug could also be used for treating eating disorders like binge eating disorder and bulimia, as well as for weight maintenance after successful weight loss. It may also be used in the prevention or treatment of cardiovascular disease.

Novo Nordisk’s Cagrisema, a combination therapy with 2.4mg semaglutide, a type of GLP-1 RAs, and with 2.4mg cagrilintide, an amylin analog, is currently in the phase 3 clinical trial.

Previous studies suggest that the novel therapy leads to more significant weight loss with fewer adverse events compared to semaglutide and cagrilintide alone.

We may need to wait for better drugs

Filing a patent application does not guarantee that a product will reach pharmacy shelves nor that it will be superior to existing medications and devices.

Wharton says drugs combining the activity of GLP-1 with the activity of other receptors like GIP, glucagon, or amylin will not necessarily have fewer side effects, and some may even have more.

Wharton tells Healthnews, “The addition to GLP1 should have increased the benefits for comorbid conditions, but we are not sure they will decrease the side effects.”