Weight loss drugs are having a moment, owing to the fact that pharmaceutical companies have figured out how to help people lose up to double-digit percentages of their body weight and start dropping a more substantial number of pounds.
Although Ozempic, Wegovy, and Rybelsus, all Novo Nordisk products, have dominated the market in the past year, Eli Lilly has its own pipeline of obesity medications. And new data the company revealed on June 23 suggest its products could give doctors and patients a greater range of options for treating the chronic condition—including more options in the form of pills, which could make them more accessible than the injectable types of medications that currently make up most of the weight-loss drug market.
At the annual meeting of the American Diabetes Association held in San Diego, Calif. from June 23 to June 26, Lilly presented results from studies of three of its weight loss drugs: tirzepatide (Mounjaro), orforglipron, and retatrutide. Tirzepatide, an injectable drug, targets two obesity-related hormones, glucagon-like peptide 1, or GLP-1, and glucose-dependent insulinotropic polypeptide, or GIP; orforglipron targets just GLP-1 but is a tablet so people can take it by mouth; and retatrutide, also an injectable therapy, targets three hormones, GLP-1, GIP, and glucagon.
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GLP-1-based drugs were originally developed to treat type 2 diabetes since they can regulate blood sugar, but researchers learned that users also lost significant amounts of weight on the medications, so pharmaceutical companies, including Novo Nordisk and Lilly, quickly pivoted to study and request approval for different doses of the medications as weight loss treatments. Cells throughout the body have receptors that recognize GLP-1, including in the gut and brain; these drugs can slow the emptying of the stomach contents, contributing to satiety, as well as regulate appetite by signaling the brain that the body has consumed enough calories, and ultimately help with weight loss.
Mounjaro was approved by the U.S. Food and Drug Administration (FDA) to treat type 2 diabetes in May 2022, and given the data in those studies showing that people taking the drug also lost weight, Lilly began studying it as a weight loss treatment in additional trials. At last year’s American Diabetes Association meeting, the company presented data showing the drug could reduce body weight by up to 22%; based on these results, the company requested the FDA in 2022 to approve the drug as an obesity therapy and the agency is expected to make a decision by the end of the year.
At this year’s meeting, Lilly presented results from another, similar study that focused on weight loss but this time among people with diabetes, a group for whom losing weight is more difficult. “We know that the patient population with type 2 diabetes has less weight reduction using any pharmacologic agent, with about 30% to 40% less weight reduction…compared to patients who don’t have diabetes,” says Dr. Nadia Ahmad, associate vice president of medical development who led the studies of tirzepatide at Lilly. “Knowing that, it’s important to study weight loss effects separately in people with type 2 diabetes.”
In the latest study, researchers found that Mounjaro can contribute to up to 15.7% weight reduction among diabetes patients, far more than previous anti-obesity therapies have produced. “That 15% weight reduction threshold is clinically important because we know that weight reduction of that magnitude is generally associated with greater improvement in obesity-related complications,” says Ahmad. “That level of weight reduction has not yet been seen in this population of diabetes patients for any obesity treatment.”
As effective as Mounjaro may be, for some patients it may not be a practical option since it requires a weekly self-injection. Injectable drugs are also generally more expensive compared to pills or tablets, since they need to be dispensed in a sterile device. That’s why Lilly, along with other pharma companies, is also exploring oral forms, such as orforglipron, of these powerful weight loss drugs. Currently, there are only two drugs in this class approved to treat obesity, semaglutide (Wegovy), and liraglutide (Saxenda) both made by Novo Nordisk. And both are injectable drugs.
The only oral GLP1-based drug, Rybelsus, is approved for treating type 2 diabetes—not for obesity. While doctors can prescribe any approved medication for any purpose off label—and therefore could prescribe Rybelsus for people without diabetes who want to lose weight—having approval specifically for weight loss means doctors can dispense the drugs with more confidence, based on studies that clarify which doses are most effective for shedding pounds.
Lilly presented data from its trial showing that its daily tablet orforglipron produces weight loss at levels similar to that of the injectable GLP1 drugs currently approved for obesity. The study, which was also published in the New England Journal of Medicine, involved more than 270 people with a body mass index (BMI) of 30 or greater, or a BMI of 27 or greater plus other risk factors associated with being overweight, such as high blood pressure, high cholesterol, heart disease, or sleep apnea. The volunteers were randomly assigned to take either an orforglipron tablet in one of four different doses once a day for nine months, or a placebo, and were followed for two weeks after completing the treatment. At the end of the study, those taking orforglipron lost 9% to 14% of their starting body weight, compared to 2% among those assigned placebo. The weight loss in the orforglipron group was similar to that achieved among people taking Saxenda (about 9% of body weight) and those taking Wegovy (about 17% of body weight).
In the next study, Ahmad says the company plans to investigate which specific doses best balance the maximum amount of weight loss that can be achieved with the minimum amount of side effects such as nausea and gastrointestinal issues the drug can cause.
Later in the conference, the company plans to present early stage results from a study of another weight loss candidate, retatrutide, a once-weekly injectable drug that targets three different obesity-related hormones.
With more options for doctors and patients to choose from in coming years, obesity treatment can, and should, become more personalized, and doctors should get better at matching patients to the medications that will work best for them. With more drug-based therapies that can lead to greater amounts of weight loss—including options that inch closer to matching those achieved by interventions such as surgery— more people for whom surgery was out of reach financially may be able to take advantage of a pharmacological weight loss regimen that could ultimately slow the growing epidemic of obesity.
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