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Weight Loss | How Does Semaglutide Work?

Semaglutide balances glucose in the body by helping the pancreas produce more insulin to regulate blood sugar levels. It’s currently FDA-approved for use by Type 2 diabetics, and is administered via subcutaneous (SQ) injection.

“…The insulin effect only occurs in a glucose-dependent fashion, so if blood sugars are normal, the semaglutide won’t trigger pancreatic insulin release — which is why it’s able to be used in patients who don’t have diabetes, with zero concern for low blood sugar,” stated Dr. Caroline Messer, a board-certified endocrinologist in New York City specializing in thyroid disease, diabetes, and weight management.  The drug also causes fullness and suppresses hunger, meaning those taking it will get full faster while eating less.

While Ozempic is the most popular brand name of semaglutide, others include Rybelsus and Wegovy. All three are being used for weight loss, but Wegovy is the only FDA-approved semaglutide for clinical obesity.

“To understand how semaglutide works for weight loss, one first needs to understand and define obesity,” according to Dr. Ania Jastreboff, associate professor in medicine and pediatrics at Yale School of Medicine and an obesity medicine physician-scientist.  Jastreboff is on the scientific advisory board for Novo Nordisk and in charge of a semaglutide clinical trial at Yale funded by Novo Nordisk.

It all starts with what she calls the “defended fat mass set point.”

“Our body wants to carry energy, and it carries that energy in the form of fat,” Jastreboff explains. “It doesn’t want us to carry not enough energy because then we would starve, and it doesn’t want us to carry too much energy because then we wouldn’t be able to do everything that we do every day. There’s a sweet spot, and we call it the defended fat mass set point.”

Because the factors that can contribute to obesity, such as highly processed foods and nonactive lifestyles, are more common than ever in today’s environment, on a population level, the U.S.’s defended fat mass set point has increased, she says. For example, if you have a BMI of 31 in 2022, 100 years ago, it might’ve been a 22.

About 42% of the population has obesity, meaning they have a chronic disease “where the body wants to carry extra fat,” Jastreboff adds.

Semaglutide works by mimicking the body’s hormones that signal to the brain about how much weight you’re carrying and reregulating the patient’s defended fat mass set point to a healthier place.

“We are decreasing their defended fat mass set point, and the consequence of that is that they lose weight,” Jastreboff says.

Ozempic (known generically as semaglutide) is an injection used to lower blood sugar and hemoglobin A1C (the part of red blood cells with glucose attached) in type two diabetics; low A1C levels decrease diabetes complications like stroke, high blood pressure and blindness.

Manufactured by Novo Nordisk, the drug is a glucagon-like peptide-1 (GLP-1) receptor agonist (a class of drugs used to treat diabetes) that was first approved for use in type two diabetics in 2017.

To lower blood sugar and A1C, the drug reacts with the body in three ways by helping the pancreas produce more insulin when blood sugar is high, slowing down the process of food leaving the stomach and stopping the liver from making and releasing too much sugar.

It’s meant to be injected once weekly in either the thigh, stomach or upper arm, with or without meals at any time of day, and patients typically start out taking a dose of 0.25 mg, though after four weeks it’s bumped up to 0.5 mg and then up to 1 mg if “more glycemic control is needed.”

Out of the more than 37 million Americans with diabetes, the vast majority—between 90% to 95%— have type two diabetes, according to the Centers for Disease Control and Prevention.

One of the side effects of Ozempic is weight loss, so some doctors have been prescribing the drug as an off-label use (the unapproved use of an approved drug) for weight loss in those without diabetes—Ozempic has not been approved by the FDA as a weight loss drug.

study published in The New England Journal of Medicine found those who took Wegovy for 68 weeks, paired with a reduced calorie diet and a more active lifestyle saw an average change of body weight of 14.9% compared to a 2.4% change in the placebo group.

These findings have caused both obese people and those slightly overweight to request Ozempic prescriptions from their doctors.

Although Ozempic isn’t approved for weight loss, Wegovy, a higher-dose version of Ozempic, was approved for weight loss by the U.S. Food and Drug Administration in 2021 for obese or overweight adults with at least one weight-related condition like diabetes or high blood pressure.

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