Demand for weight-loss drugs poses challenges
Associated Press
The injectable drug Ozempic is prescribed for type 2 diabetes but has found to offer weight-loss benefits.
Associated Press
Drugs like Ozempic, Mounjaro and Wegovy prescribed for type 2 diabetes have proven to be life-changing for many patients struggling with lifelong obesity.
Courtesy of AHN
Dr. Fahad Zubair, Medical Director of Obesity and Nutrition Medicine at Allegheny Health Network
It seems as if a new drug touting weight-loss benefits has made headlines or hit the market every week over the past year. Drugs like Ozempic, Mounjaro and Wegovy have proven to be life-changing for many patients struggling with lifelong obesity.
While the drugs appear to offer a long-term solution, doctors are often forced to prescribe them off-brand, since most are only approved by the U.S. Food and Drug Administration (FDA) to treat diabetes. Insurers have begun cracking down on paying for off-brand use and some have sent letters to doctors warning them to stop prescribing the very expensive medications for anything but diabetes in order to cut costs and prevent nationwide shortages. On top of all of this comes word of new outstanding phase two clinical trial results for another drug called retatrutide, which may be even more effective for losing weight and lowering blood sugar than the others.
A study published in The New England Journal of Medicine compared 338 adults with obesity taking either retatrutide injections or a placebo for four months. Researchers found those taking the actual drug at the highest dose of 12 milligrams lost nearly 25% of their total body weight. The placebo group lost only 2% of their body weight. Like Ozempic and Wegovy, retatrutide is also a glucagon-like peptide-1 (GLP-1) inhibitor, but it also works on two extra hormones to lower blood sugar and glucagon to help burn more energy and prevent hunger cravings. It’s still an experimental drug and phase three clinical trials will come next.
“The future for weight loss treatment is very promising,” says Dr. Fahad Zubair, Medical Director of Obesity and Nutrition Medicine at Allegheny Health Network (AHN). “Not only do we have FDA-approved GLP 1-RA to use, but there are also many trials underway for drugs that work in a similar fashion and for those that may act on more than one hormone or receptor.”
Zubair admits one of the biggest challenges is the cost of such medications. Still, he’s hopeful they can help many people in the future. “Having more FDA-approved drug options, along with more pharmaceutical companies getting involved in the development of medications to treat obesity, will likely improve access and reduce costs for patients.”
How they work
Semaglutide is a member of the Glucagon-like Peptide-1 Receptor Agonist (GLP-1 RA) class of medications. It binds to and activates the GLP-1 receptor, which is the target for native GLP-1 hormone. “It stimulates insulin secretion, lowers glucagon secretion, and delays gastric emptying,” Zubair said. “The glucose-dependent insulin release, suppression of glucagon release, and suppressed hepatic gluconeogenesis (glucose synthesis in the liver) reduces both fasting and post-meal glucose levels. Ultimately, this leads to better overall glucose control for type two diabetics.”
When it comes to using the drugs for weight loss, some of those same properties can help by delaying stomach emptying so you feel fuller longer, reducing appetite and hunger.
“They also work in the central nervous system to reduce feelings of hunger and increase measures of satiety or that ‘full’ feeling,” Zubair explained. “This reduces the total energy and caloric intake resulting in weight loss. These are administered as subcutaneous injections.”
What will FDA do?
There are currently two GLP-1 RA drugs approved by the FDA for weight loss. The first is once-daily Saxenda, and the second is once-weekly Wegovy. In addition to weight loss, they are also approved for use for weight maintenance if an individual is successful with use.
“There are other drugs in the class such as Ozempic, Monjauro, Rybelsus (oral GLP-1 RA), which are approved by the FDA for use in the treatment of type two diabetes only,” Zubair said. “But given the similar mechanism of action, they can also help with weight loss. There are many clinical trials currently underway for drugs with similar action, which will likely bring about more treatment options for patients.”
The high demand for the drugs by people wanting to use them for weight loss has led some insurers to refuse to cover them or forbid doctors to prescribe them for use other than to treat diabetes. “The increased demand for this class of weight loss drugs, along with off-label prescribing, has resulted in national drug shortages,” said Zubair. “Stricter guidelines are needed for off-label prescribing to avoid sustained shortages of drugs like Ozempic, which type two diabetes patients need for blood sugar management.” The drugs also don’t come cheap, with copayments often running more than $100 for a 90-day supply, even for those lucky enough to have insurance cover the prescriptions.
Zubair does see the pendulum swinging when it comes to regulatory approval for more of these drugs as weight-loss tools. The stumbling block may be the high prices, and that remains a problem for manufacturers and insurers to solve. While these drugs may seem like the answer for millions of Americans when it comes to weight loss, Zubair urges caution.
“It is important for patients to understand how weight is regulated,” he said. “Acquiring more knowledge and improving educational resources should be the main goal. None of the available weight loss medications are effective without the right changes in lifestyle habits. The change needed is different and unique to everyone and tailored to what their individual health requires, and the battle is lifelong. After successful weight loss, the challenge of healthy weight maintenance remains.”