“Goodbye, Ozempic: A New Class of Drugs Is Transforming Obesity Care. They Are Not All the Same”, 2023-06-27 ():
Earlier this year, my colleague Yasmin Tayag wrote that Ozempic—the diabetes drug that has become a cultural phenomenon in its off-label use for weight-loss—was about to be old news. She was right.
Over the past few days, presentations at the American Diabetes Association meeting in San Diego have delivered a slew of findings that suggest the Age of Ozempic is already over. Taking its place: a parade of better treatments for obesity. A new, oral form of semaglutide works about as well as Ozempic or Wegovy, which are injectable versions of the same [all owned by Novo Nordisk]; so does another pill containing a drug called orforglipron [Eli Lilly]. New data also hint that shots containing tirzepatide [Eli Lilly] or survodutide [Boehringer Ingelheim] may end up working better than semaglutide, and that a compound called retatrutide [Eli Lilly] is perhaps the best of all, with effects approaching those of bariatric surgery. I won’t even bore you with the news about pemvidutide (Altimune), lotiglipron [Pfizer], and danuglipron [Pfizer]!
In other words, Ozempic is old news, and sooner than we thought. The drug will still be widely used, but a bewildering array of medications for obesity is advancing through development, and in the coming years, they will become a bewildering array of options for patients: Some drugs may be cheaper or more convenient than the others; some may be stronger; some may eventually have fewer nasty side effects or more consistent benefits across the population. That only makes it more disturbing that, even as the drug Ozempic is becoming obsolete, the name Ozempic, as the shorthand for a class of drugs, seems destined to live on.
…It’s true that all of these drugs are similar to a point. The reports from San Diego describe a set of medications with at least one common source of action: They each serve to activate a receptor for a hormone called GLP-1, which stifles appetite and causes insulin to be released (among other bodily effects). Liraglutide was the first such drug to be approved as a treatment for obesity, and has been available for that use since 2014. Another drug that hits the same receptor, dulaglutide, has also been available to treat diabetes for years. Semaglutide arrived a few years later, first as a shot for diabetes (‘Ozempic’), then in pill form (‘Rybelsus’), and finally as a higher-dose injection that was approved for weight loss (‘Wegovy’). More drugs of this kind but made from smaller molecules (and cheaper to produce) are in the works, including two of the new “Ozempic pills”, orforglipron and danuglipron. Any of these GLP-1-targeting drugs can suppress your desire to eat, leading to at least some loss of weight. Any of them might give you nausea, stomach pain, and diarrhea. In that sense, they are all indubitably Ozemp-ish. But they are not Ozempic.
Other drugs that get squeezed under the Ozempic umbrella do other things. Mounjaro contains tirzepatide, which activates the GLP-1 receptor like the other drugs but also another receptor for a hormone known as GIP. Survodutide, one of the drugs presented over the weekend in San Diego, targets both GLP-1 and glucagon receptors. Retatrutide, perhaps the most promising of the obesity medications now in the pipeline, activates GLP-1, GIP, and glucagon receptors. Do these drugs affect the same broad system of so-called incretin hormones as Ozempic? Sure. Do they lead to weight loss? Very much so. Can they upset your stomach to an uncomfortable degree? Of course. But they’re less like siblings of Ozempic than cousins.
“These drugs have different properties”, Fatima Cody Stanford, an obesity-medicine physician at Massachusetts General Hospital and Harvard Medical School, told me. “They have different mechanisms of action.” Semaglutide limits glucagon secretion, for example, whereas tirzepatide’s effects on glucagon seem to go in both directions. Stanford says the latter drug does more to change the body’s levels of cholesterol. In the long term, such distinctions will help determine how these new drugs fit together to define the future of obesity treatment. Ideally, patients and their doctors will discuss the pros and cons of each.