Academics from the UV School of Medicine take part in important WHO study
10/11/2025
A group of professors and researchers from the School of Medicine at the Universidad de Valparaíso has published an important study commissioned by the World Health Organisation (WHO) to analyse the effects of weight loss using the injectable GLP-1 drugs, tirzepatide, semaglutide and liraglutide.
The study, consisting of three systematic reviews by the Cochrane Collaboration, included all international clinical trials conducted to date and found evidence that these injectable weight-loss drugs produce clinically significant weight loss in people who have been prescribed them as medical treatment. However, the analysis also warns that the fact that the trials were conducted by the pharmaceutical industry raises certain doubts about the independence of their results.
The corresponding author of the review was Dr Eva Madrid, director of the Interdisciplinary Centre for Health Studies (CIESAL) at the Faculty of Medicine of the Universidad de Valparaíso and leader of the Ibero-American Cochrane Evidence Synthesis Unit. She co-led the work with Dr Juan Franco, from Heinrich Heine University in Düsseldorf, Germany. The group of academics from the UV School of Medicine was led by CIESAL researchers Dr Nicolás Meza and Dr Javier Bracchiglione, lead authors of two of the reviews, with the collaboration of Victoria Novik, Gabriel Lazcano, Daniel Poloni, Miranda Ocara, Francisca Rinaldi and student Felipe Álvarez.
The analyses were mainly carried out by the Ibero-American Evidence Synthesis Unit (of which CIESAL researchers are members), the Ibero-American Cochrane Network, and the Cochrane Evidence Synthesis Unit Germany/UK. The WHO commissioned the study to inform future clinical guidelines on the use of these drugs to treat obesity. WHO clinical guidelines establish evidence-based recommendations to improve healthcare worldwide by offering guidance to optimise clinical decisions, standardise practice, and improve patient health outcomes in different countries.
The reviews examined the effectiveness of the weight-loss drugs tirzepatide, semaglutide and liraglutide — which are known as GLP-1 (glucagon-like peptide-1) receptor agonists — and found that they all produce clinically significant weight loss compared to a placebo. The best known in Chile are Ozempic, Saxenda, Mounjaro and Victoza.
However, Dr Madrid cautions that the evidence regarding their long-term and secondary effects is limited or uncertain, partly due to potential conflicts of interest.
Origin of GLP-1s
GLP-1 drugs were originally developed to treat type 2 diabetes, and they were first used clinically in the mid-2000s. In patients with this condition, particularly those with heart or kidney disease, these drugs improved blood glucose control, reduced the risk of cardiac and renal complications, aided weight loss and decreased the risk of premature death.
More recently, trials have been conducted to study the use of these drugs in people with obesity. These trials have proven that the drugs mimic the activity of a natural hormone that slows digestion and makes people feel full for longer. GLP-1 drugs are currently authorised in Spain and other countries to aid weight control when used alongside a low-calorie diet and exercise for people who are obese or overweight and have weight-related health problems.
Weight loss, with possible rebound effect
All of the systematic reviews conducted by researchers at the Ibero-American Cochrane Centre found that, compared to a placebo, tirzepatide, semaglutide and liraglutide produced significant weight loss after one or two years, with these effects likely to continue as long as treatment is ongoing.
According to the analyses, tirzepatide — injected once a week — resulted in an approximate 16 per cent weight reduction after twelve to eighteen months. Evidence from eight randomised controlled trials involving 3,361 people also suggested that these effects could be maintained for up to three and a half years, although long-term safety data were limited.
As for semaglutide ― also administered by injection once a week ― it was found to reduce body weight by almost 11 per cent after 24 to 68 weeks, with the effects likely to persist for up to two years, according to data from 18 randomised controlled trials involving 27,949 participants. While this medication increased the likelihood of achieving at least five per cent body weight loss, it was also associated with higher rates of mild to moderate digestive side effects. “Semaglutide represents a powerful tool in the management of obesity, with clinically relevant effects,” commented CIESAL researcher Dr Javier Bracchiglione, one of the lead authors of the article. “It is a relatively new drug, and we still do not know for sure what happens after its use is discontinued. Some studies suggest that there could be a rebound effect on weight, but that was not the main focus of our review,” he added. According to Bracchiglione, there is still insufficient data to draw solid conclusions about the possible adverse effects and safety of the drug.
Finally, liraglutide — administered by daily injection — resulted in a smaller average weight reduction of between four and five per cent, according to 24 trials involving 9,937 participants. Nevertheless, it increased the proportion of people who achieved significant weight loss compared to those taking a placebo. Evidence of longer-term effects (beyond two years) was scarcer. “Liraglutide remains a useful alternative in the management of obesity, especially in contexts where other GLP-1 receptor agonists are unavailable or unaffordable,” said Dr Nicolás Meza, CIESAL researcher and fellow lead author of the article. “However, this is not an adverse-effect-free drug, and its use should form part of a comprehensive plan to change habits, accompanied by close clinical monitoring,” he added.
It should be noted that, in all reviews, there was little or no difference between these drugs and the placebo in terms of serious cardiovascular events, quality of life, or mortality. However, adverse events, specifically nausea and digestive symptoms, were more common in those receiving GLP-1 drugs. This led some people to discontinue treatment due to these side effects.
“These drugs have the potential to produce considerable weight loss, especially in the first year,” explained Juan Franco, the lead author of one of the reviews and a researcher at Heinrich Heine University in Düsseldorf, Germany, who is also affiliated with the Cochrane Synthesis Unit Germany/UK. “It is an exciting time after decades of failed attempts to find effective treatments for people with obesity,” he added.
Dr Eva Madrid and Dr Juan Franco led the study and were its corresponding authors
Independent research
Dr Eva Madrid points out that most of the studies included in the systematic reviews were funded by the pharmaceutical industry, which played a significant role in planning, executing, analysing and reporting the results. In her view, this raises questions about potential conflicts of interest, highlighting the need for future research to be independent of industry interests.
She and the other authors emphasised that wider use of these drugs must consider the social and commercial determinants of health, such as access, affordability and coverage, to avoid exacerbating existing health inequalities among people with obesity. Currently, the high price of semaglutide and tirzepatide limits access to these treatments, while the expired patent on liraglutide has allowed more affordable generic versions to become available. The patent on semaglutide is also set to expire in 2026.
The studies included in the three reviews were primarily conducted in middle- and high-income countries, with limited representation from regions such as Africa, Central America and Southeast Asia. Given the diversity of body composition, diet and health behaviours among different populations, the authors emphasise the importance of evaluating how these drugs work in diverse global contexts.
“We need more data on long-term effects and other cardiovascular health outcomes, especially in lower-risk individuals,” says Eva Madrid.
“Weight regain after discontinuing treatment could affect the long-term sustainability of the observed benefits. Therefore, more independent studies with a public health perspective are needed,” says the director of CIESAL at the UV Faculty of Medicine.
In line with this, Drs Madrid and Franco conclude that the reviews highlight the need for independent, long-term research to inform clinical and public health decisions, and to establish the role of GLP-1 receptor agonists in long-term weight control. They anticipate that, based on their results, the WHO will publish clinical guidelines in December recommending the use of GLP-1 for the management of obesity and being overweight.
For further information, see the studies and press releases about the study:
Tirzepatide for adults living with obesity
Liraglutide for adults living with obesity