After the rise of weight loss injections like Wegovy and Zepbound, a Keck Medicine of USC doctor talks about what’s next in obesity treatment.
Many have hoped for a magic weight loss pill for years, as losing weight is hard to do, and even harder to sustain. For the past few years, that pill might have come in the form of an injectable. With the rise of medications such as Wegovy and Zepbound, some might think we have found the answer. But scientists and doctors say there’s still more to come when it comes to perfecting weight loss drugs and treating obesity. Here’s what scientific breakthroughs doctors are looking forward to seeing in the field.
Targeting more receptors for more weight loss
Current approved weight loss injections include semaglutide (Wegovy or Ozempic when used for diabetes), tirzepatide (Zepbound or Mounjaro when used for diabetes) and liraglutide (Saxenda or Victoza when used for diabetes). Semaglutide and liraglutide work by targeting one gut hormone receptor. Tirzepatide is different, because it targets two, making it a dual agonist. And researchers are working on making medicines that target even more hormones to achieve even better results.
“Not surprisingly, when you start to target more and more of these bad hormones, the amount of weight loss achieved goes up even more,” says Kurt Hong, MD, an internal medicine and clinical nutrition physician at Keck Medicine of USC. “The next one that may get approved by the FDA is actually considered a triple agonist.” But that drug, which is being developed by Eli Lilly, is still in clinical trials and hasn’t been approved by the Federal Drug Administration, yet. But based on the Phase II data, Hong says he is excited about the future clinical potential of this triple agonist drug.
More injectables, less pills
Weight loss medications are nothing new, says Hong, and oral stimulant medications for weight loss have been in use since the 1960s. The difference with the latest weight loss injections is their effectiveness and easier use than older-generation injectables. Instead of being injected daily, they are injected weekly, making it easier for the average patient to manage, Hong says.
“With Zepbound, we have actually seen weight loss upwards of 20%-22% of a patient’s excess body weight,” Hong says. This is exciting for patients and doctors, because it’s comparable to the amount of weight loss seen with bariatric surgery, but the medications are a much less invasive treatment.
“There are a couple additional medications currently on the horizon that will probably all come out within the next couple of years, and moving forward, almost all the medications are going to be injectable,” Hong says.
Lower adverse side effects, lower cost
Right now, there are two main problems for patients when using the current injectable weight loss drugs: cost and side effects, Hong says. Researchers are still figuring out how to reduce side effects from these drugs and working on increasing manufacturing to make the drugs more affordable for patients.
“A lot of these injectable medications can cause nausea, reflux, bloating, constipation and diarrhea,” Hong says, adding that these effects are seen in about 10%-20% of patients.
And in terms of cost, right now there’s been a manufacturing shortage as demand has skyrocketed for these drugs. But Hong predicts the price will come down.
“With any medication, the longer they have been on the market, sometimes the cost will come down a little bit,” he says. “All these drugs are still relatively new – coming to market within the past few years – but we haven’t quite gotten to that point yet.”
Additionally, many insurance companies won’t cover the cost of these drugs for weight loss alone, without the presence of diabetes or some other comorbid condition. If these medications are not covered by insurance, they are about $1,200 a month.
“It’s unfortunate, because for most people it’s not realistic in terms of pricing, but there are ways to see whether or not patients can get covered,” Hong says. If patients can prove they have tried to lose weight in traditional ways like diet and exercise and have failed, doctors can sometimes appeal to the health insurance companies to get the GLP-1 drugs covered.
Keeping muscle, keeping off fat
Another problem with current weight loss drugs is that people tend to regain weight if they stop taking the drugs, says Dr. Hong. Additionally, sometimes while losing weight, people can lose some muscle mass, in addition to fat.
Some drug makers are working to address this problem. BioAge labs is currently studying a drug, azelaprag, and early clinical studies have shown it might prevent muscle loss and increase fat loss when taken in conjunction with weight loss drug Zepbound.
Treatment for other conditions beyond obesity and diabetes
But beyond the negative side effects, there’s also some positive side effects of these medications that are being studied.
“Besides helping with diabetes and weight loss, there are also some very potent anti-inflammatory benefits,” Hong says. Keck Medicine of USC physicians are currently conducting a clinical trial to study the side effects of these drugs in people with fatty liver disease.
“There’s also a kind of collaboration that’s being formed to study the use of these medications in patients who are undergoing orthopaedic surgeries such as hip or knee replacements,” he said, adding that it’s believed these medications could help patients lose weight before undergoing orthopaedic surgery.
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