New GLP-1 drug guidelines recently recommended by the World Health Organization (WHO) were reviewed in a JAMA article published online a few days ago. One major point? Global obesity rates have been rising substantially for more than 30 years. But change is in the air!
To illustrate: adult obesity in the US peaked at a record high of nearly 40% 3 years ago. That now is changing. In 2025 the obesity rate dropped to 37%, a decrease suggesting that last year the US had 7.6 million fewer obese adults living in this country. Wow! What happened? You guessed it. JAMA points out that this drop in obesity coincides with a notable uptick in the use of glucagon-like peptide-1 (GLP-1) receptor agonists, a class of drugs approved for the treatment of obesity in the US market earlier this decade, and one I’ve discussed here before (see here).
The WHO guidance recognizes obesity as a “complex, relapsing, chronic disease” that requires ongoing, lifelong care. In a nutshell, the guidance offers two major recommendations: 1) GLP-1 therapies may be used by adults, excluding pregnant women, for long-term obesity treatment and 2) “intensive behavioral interventions” may be offered to those taking GLP-1 medications.
Importantly, it should be emphasized that possible side effects of GLP-1 drugs are still unknown. “There is an evidence gap,” said a physician who coauthored the JAMA article. “First of all, we don’t know if this is a lifelong therapy. The long-term use and safety of the medicine are not actually known.” She went on to mention rare adverse effects of GLP-1 that have been reported, such as gastrointestinal issues—nausea, vomiting, and diarrhea—and potential risks of acute pancreatitis or nonarteritic anterior ischemic optic neuropathy. Almost certainly, other side effects will be discovered, but probably none so dramatic as that of an earlier magical medication. See that story below.
An important historical note
“On September 4, 1948, the first dose of a glucocorticoid was administered to a bed-ridden 24-year-old woman with rheumatoid arthritis. The treatment of rheumatoid arthritis with cortisone resulted in a dramatic improvement in the levels of inflammation, function and sense of well-being. That patient’s ability to rise from bed and walk the following day astonished her physicians and ultimately marked a new era in the lives of millions of patients around the world. Just 23 days after the first dose of steroid, the first toxicities of this new therapeutic approach were reported. The next day, the first steroid taper began. By 1960 [some 12 year later], the full range of 80+ steroid-toxicities had been described. Although debates raged about the proper use of steroids, by then the drugs had become entrenched as “necessary evils” in the struggle to manage inflammatory disease.” To read this complete article about the many steroidal side effects, such as osteoporosis, fractures, hypertension, and more, see here.
It seems unlikely that GLP-1 drugs will lead to such dramatic side effects, but it may be worth remembering that GLP-1 drugs, like glucocorticoid drugs, are close cousins of hormones that our bodies produce normally. Here’s how the physician quoted above mentioned the possible risks. “If hundreds of millions of people are receiving this medicine (GLP-1 drugs) in the next 10 years, even the most rare of adverse effects can become a considerable absolute number. The current safety data is very inconclusive. We need many more studies.”
More about the new GLP-1 drug guidelines
The WHO recognizes that GLP-1 drugs are a not a stand-alone fix but rather part of a comprehensive treatment strategy that combines pharmacology, behavioral support focused on a healthy diet and physical activity, and long-term follow-up. As one expert summed up weight control efforts: “While these therapies represent a breakthrough in obesity treatment, medicine alone will not solve the problem.” Another added, “GLP-1 drugs aren’t a magic bullet.”
Another critical area of consideration within the guidance is the long-term, or possibly lifetime, sustainability of GLP-1 drugs (probably not desirable because of possible side effects, not to mention heavy costs). It is noteworthy that more than half of individuals who initiate the medication stop taking it within a year. Terminating treatment often leads to a regain of weight. NOTE THAT LAST POINT!
A final thought about obesity treatments. What do you think of this approach?
This weekend, a pediatrician from Pakistan commented in JAMA on the journal’s review of WHO’s guidelines. Here is part of what he wrote, “I read so many articles on JAMA regarding the GLP-1 role in obesity that it seems like JAMA is promoting this drug, and it’s an advertising platform. When there are so many simple treatment modalities available, then what is the fun in discovering costly treatments? Treating obesity with such expensive medications and with bariatric surgeries seems very strange. Yes, true that obesity is a chronic condition with long-term adverse health outcomes, but there are many simpler and cheaper preventive and treatment modalities available. . . In a country like Pakistan, I have seen physicians, qualified from the US and the UK, who are treating obesity without prescribing a single drug. Just by simple fasting, they are treating obesity with remarkable results. . . My suggestion is, whenever there are articles [in JAMA] regarding the role of a medicine or surgery in obesity management, there must be dedicated paragraphs for obesity prevention in each of these articles. These authors must be bound to discuss the adverse effects of breast milk substitutes, sugar-sweetened beverages, and fast food in every article relating to obesity. Likewise, the role of physical activity and fasting must be highlighted in each of these articles. So that these articles should not give the impression that a specific drug or surgery is the only treatment for obesity.“
