Upcoming GLP-1 medication may drastically transform weight management therapy.
Part of his hesitation: He has a fear of injections, and all the approved weight loss drugs in this category are administered as weekly self-injections.
"This has been quite challenging," Holz, 44, stated after a week into treatment.
However, the need for injections might change soon. Approximately a dozen experimental weight loss drugs that are intended to be taken as pills are currently undergoing clinical trials, with the most advanced now in the final stage of testing.
According to Dr. Jody Dushay, an assistant professor of medicine at Harvard Medical School and an attending physician in endocrinology at Beth Israel Deaconess Medical Center, these pills could significantly shift the landscape of weight management.
The field is already undergoing a transformation, with millions of people in the US currently using semaglutide and tirzepatide for weight loss (and diabetes under the brand names Ozempic and Mounjaro).
Dushay expects that pill versions of GLP-1 drugs could alleviate shortages, be more affordable, and improve convenience. However, she and other doctors also highlight concerns about misuse, which could become more common with daily pills instead of weekly injections. They might make it simpler to consume more than recommended or share medication inappropriately.
"There's a lot to learn about the oral versions," Dushay said.
Oral Semaglutide
The most advanced oral pills contain a version of semaglutide, the active ingredient in Ozempic and Wegovy, developed by Novo Nordisk. In a late-stage study last year, Novo Nordisk reported that the daily pill resulted in an average weight loss of 15% over 68 weeks for individuals without diabetes, a similar result to what was observed in trials for Wegovy.
However, Novo Nordisk has yet to confirm whether they've filed for approval of the drug from the US Food and Drug Administration, and sales of the oral form of semaglutide for type 2 diabetes, approved as Rybelsus, have been considerably less than those for injectable Ozempic.
While it's a pill, Rybelsus also poses some challenges: It must be taken daily on an empty stomach, with no eating, drinking, or taking other medications for at least 30 minutes. Doctors have reported that it may not be as effective as injections and still produces side effects.
Moreover, the dose of oral semaglutide for obesity is much higher, which could lead to more pronounced side effects, according to Dr. Jorge Moreno, an obesity specialist and assistant professor of medicine at the Yale School of Medicine. The dose for weight loss is 25-50 milligrams a day, compared to 14 milligrams for Rybelsus and a maximum of 2.4 milligrams a week for injections of Wegovy.
"I have seen more significant gastrointestinal side effects with oral semaglutide than with injections," Moreno said, adding that he is unsure "what differences in side effects may occur when using such high doses of semaglutide compared with the injectable dose."
In the trial, Novo Nordisk stated that the "vast majority" of side effects of oral semaglutide were "mild to moderate and diminished over time." However, all GLP-1 drugs are associated with side effects such as nausea, vomiting, and abdominal pain, although not all patients experience them.
The Oral GLP-1 Race
Immediately following oral semaglutide is a group of drugs headed by Eli Lilly's orforglipron, an oral medication that targets GLP-1, a hormone known for its role in insulin regulation, appetite, and digestion.
Lilly, which also manufactures Zepbound and Mounjaro, reported last year that a midstage trial found that people taking orforglipron for 36 weeks lost an average of 15% of their body weight, which is about the same amount as oral semaglutide in less time. Results from a later-stage study are expected in the first half of next year, according to Evan Seigerman, a research analyst with financial firm BMO Capital Markets.
Drugmakers including Pfizer and Roche, as well as smaller companies like Structure Therapeutics, Terns Pharmaceuticals, and Viking Therapeutics, also have oral weight loss drugs in earlier stages of development, according to BMO research.
And Novo Nordisk isn't limiting themselves to semaglutide; they have multiple programs in the early stages of development to bring next-generation weight loss pills to market.
Earlier this month, data presented at the European Association for the Study of Diabetes conference showed that study participants who got a higher dose of the experimental drug amycretin lost an average of 13% of their body weight in 12 weeks. The drug targets both GLP-1 and another hormone, amylin.
Novo Nordisk also agreed to invest up to $1.1 billion last year to acquire Inversago Pharma, gaining an experimental oral drug called monlunabant that's designed to block a cannabinoid receptor important in regulating appetite. Results from a midstage study on that drug are expected this year, according to BMO's research.
Not every one of these experimental medications might make it to market, yet they could potentially serve as "long-term maintenance doses" for individuals who've significantly reduced their weight through injectable medications, according to Dushay's observation.
These medicines could prove to be an "excellent alternative to regular injections," Dushay suggested. "They may not be as potent for substantial weight loss as the initial therapy, but they can be incredibly effective for maintaining weight loss, which is arguably a more significant and crucial goal for long-term health benefits."
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Holz, who keeps a close eye on the weight loss drug scene as part of his health care strategy for an investment firm, expressed his desire to shift to an oral medication, if possible, instead of the weekly injection he's currently using, in the event that a suitable alternative emerges.
In a period of three months, Holz claimed to have lost more than 10% of his body weight. His enthusiasm for GLP-1 drugs extends beyond weight loss, as he appreciates their positive impact on heart health and other potential health benefits.
The weekly injection, which he initially found concerning, turned out to be almost painless, Holz said. He attributed this to the drug manufacturers' focus on improving the experience with autoinjector pens, and lamented that he had not begun using the treatment sooner.
The potential shift to oral weight loss drugs could significantly improve Holz's convenience, as he has a fear of injections.
With the expected introduction of oral GLP-1 drugs, such as oral semaglutide, there might be a reduction in the misuse of these medications due to their daily dosage.
