The World Health Organization (WHO) has finally made its recommendations on using glucagon-like peptide-1 (GLP-1) therapeutics for weight loss, though it remains to be seen whether it changes their status for prescribing or their price.
The announcement was made on December 1, with the WHO offering two recommendations for GLP-1 drugs that include Wegovy (semaglutide) and Mounjaro (tirzepatide) for long-term use to manage obesity. The body also recommends the medications be used in conjunction with other strategies including counseling and ongoing monitoring of patients by clinicians. They are as follows:
Recommendation #1: In adults living with obesity, long-term GLP-1 therapies may be used for weight management. This conditional recommendation is supported by moderate-certainty evidence from ongoing trials for their effectiveness in achieving clinically meaningful weight loss and broad metabolic benefits, together with cost, health system preparedness, and potential equity implications.
Recommendation #2: Those prescribed GLP-1 therapies benefit from structured behavioral therapy, including goal setting for physical activity and diet, energy intake restriction, regular counseling sessions, and ongoing assessment of progress. This conditional recommendation is supported by low-certainty evidence of intensive behavioral therapy enhancing the efficacy of GLP-1 therapies across tirzepatide, semaglutide, and liraglutide.
"The guideline identifies the challenge of 'obesity' and the need for more research on these drugs," said Professor Elaine Rush from Auckland University of Technology. "These drugs are expensive, and the recommendation is that intensive behavioural therapy and weekly counselling sessions are provided alongside the medication. Cost effectiveness is not known."
While the WHO emphasized that governments and healthcare systems need to make GLP-1s affordable for people with obesity, it noted that the drugs alone are not a fix-all for individuals nor a solution, on their own, for a worldwide health crisis.
"The world has moved in 100 years from a state where global malnutrition was the major global health crisis to a state where excess weight now is," said Peter Shepherd, Professor of Molecular Medicine & Pathology at The University of Auckland. "This is because obesity is a major driver in development of heart disease, kidney disease, type-2 diabetes and certain cancers that shorten lifespans and reduce quality of life. A major barrier to effective treatment of obesity has been a failure to understand the biology that is driving our appetite and fat accumulation. This has changed drastically and we now understand that drugs that mimic a natural hormone called GLP1 (e.g. Wegovy and Ozempic) can safely and effectively reduce appetite and weight."
However, Shepherd also points out that the cost of the drugs remain prohibitive and exposes the healthcare wealth divide around the world.
"While many people report significant savings on food costs while on these drugs, this remains unaffordable for many individuals," he said. "The good news is the patent for the main ingredient runs out soon and many competitors are poised to enter the market, so prices will surely fall."
Another concern with the class of drugs is because of their meteoric rise, we don't have long-term studies on potential health complications. This week, Australia's Therapeutic Goods Administration (TGA) released a safety alert, updating product warnings for GLP-1 drugs to better cover "the potential risk of suicidal thoughts or behaviours."
Recently, trial results found that while people lost weight and had improved health markers while on tirzepatide (Mounjaro) for 36 weeks, once off the medication those cardiometabolic benefits began to disappear. An average of 25% of the weight lost had been regained following 12 months abstinence.
"The other issue is what long term side effects might be," Shepherd said. "We already know muscle loss caused by these drugs is a potential issue, particularly in older people so careful monitoring will be required. However, the patient-led demand driving the use of these drugs has led to the first ever reduction in rates of obesity in the USA, showing the people affected by obesity really want a solution. This article shows that global health bodies now recognise that medical treatments are now formally recognised as one important tool in reversing the tide of obesity."
Meanwhile, Rush also points out that more focus should be on preventing the obesity epidemic to start with – particularly as studies emerge that many of the benefits of GLP-1 medications may not be sustained once use is discontinued.
"We do know that for most obesity is a form of malnutrition, driven by the environment, i.e. a poor quality food supply, lack of physical activity, poverty, pollution, and it is intergenerational," she said. "Rather than invest in these drugs in the long term we should invest in reducing child poverty (and improving school lunches) so that we support a better future and get a better return on investment in the long run."
The research was published in the journal JAMA.
Source: World Health Organization via Scimex
