WHO reviews find Ozempic and GLP-1 drugs effective but raise long-term questions

Three systematic reviews commissioned by the World Health Organization and published in March 2025 confirm what clinical trials have been showing for several years: GLP-1 receptor agonist drugs work for weight loss. Semaglutide, sold as Ozempic for diabetes management and Wegovy for obesity, produced average body weight reductions of 12 to 15 percent over 68 weeks in the STEP trial program. Tirzepatide, sold as Mounjaro and Zepbound, achieved average reductions of up to 22.5 percent in the SURMOUNT-1 trial. The WHO reviews synthesized data from these and dozens of other studies covering more than 30,000 patients.

The reviews were commissioned to inform the WHO's updated global guidance on obesity treatment, which is expected to be released later in 2025. The WHO's existing guidance was written before GLP-1 drugs became widely available and does not address them substantively. Given that over 890 million adults worldwide are classified as obese according to the WHO's own 2024 global health estimates, any update to official guidance carries significant implications for national health systems deciding whether and how to cover these medications.

What the evidence actually shows about weight loss results

The first of the three WHO reviews focused on clinical efficacy and found that GLP-1 drugs consistently outperformed placebo and behavioral intervention alone across multiple weight categories and metabolic conditions. The average weight reduction across studies was 11.4 percent for semaglutide at 2.4 milligrams weekly and 18.9 percent for tirzepatide at 15 milligrams weekly, the highest approved doses. For context, a 10 percent weight reduction in a person with obesity is associated with clinically meaningful improvements in blood pressure, blood sugar, and sleep apnea severity.

The cardiovascular benefits documented in the SELECT trial, published in the New England Journal of Medicine in 2023, were also noted by the WHO reviewers. That trial followed 17,604 adults with overweight or obesity and established cardiovascular disease for a median of 40 months. Semaglutide reduced major cardiovascular events, including heart attack and stroke, by 20 percent compared to placebo. This cardiovascular effect appears to be partly independent of weight loss, operating through anti-inflammatory and metabolic pathways that are still being studied.

The weight regain problem after stopping medication

The second WHO review focused on what happens when patients stop taking GLP-1 drugs, and the findings are consistent with what clinical trials have already documented. The STEP 4 extension trial, in which participants who had been taking semaglutide were switched to placebo, showed that patients regained an average of two-thirds of their lost weight within one year of stopping. Tirzepatide withdrawal data from the SURMOUNT-4 trial showed similar patterns, with participants regaining approximately 14 percentage points of the weight they had lost over 88 weeks of active treatment within 52 weeks of switching to placebo.

This rapid regain reflects the mechanism by which these drugs work. GLP-1 receptor agonists suppress appetite by mimicking the hormone GLP-1, which is naturally released after eating and signals satiety to the brain. When the drug is stopped, the appetite-suppressing signal disappears, and the body's weight-regulating set point, which has not been permanently altered by the medication, drives eating behavior back toward the baseline that produced the original weight. The WHO review framed this as an argument for treating obesity as a chronic condition requiring long-term pharmacological management rather than a short-term intervention.

Side effects and the patients most likely to discontinue

The third WHO review covered safety and tolerability. Gastrointestinal side effects are the most common reason patients stop taking GLP-1 drugs. Nausea occurs in approximately 44 percent of semaglutide users in the first weeks of treatment, and vomiting in about 24 percent, according to pooled data from the STEP trials. For most patients these effects diminish after the first two to four months, but they are severe enough to cause permanent discontinuation in roughly 7 percent of trial participants.

More serious adverse events noted in the review include a small but statistically significant increased risk of gallbladder disease, which has been documented across multiple semaglutide trials at an incidence of about 1.5 percent in treated groups compared to 0.8 percent in placebo groups. Pancreatitis has been flagged in drug labeling but the absolute risk appears low, estimated at approximately 0.3 cases per 1,000 patient-years in observational studies. The WHO review also noted that the long-term effects on thyroid function and thyroid cancer risk remain under surveillance, given preclinical data showing GLP-1 receptor expression in thyroid C-cells.

Access and affordability as a public health constraint

The WHO reviews addressed access explicitly, which distinguishes them from purely clinical evaluations. Semaglutide's list price in the United States is approximately $1,350 per month for Wegovy, while tirzepatide's Zepbound is listed at around $1,060 per month. Neither is covered by Medicare for obesity treatment under current US law, and coverage through private insurance is inconsistent. In lower-income countries, the drugs are effectively unavailable at any price for most patients.

Novo Nordisk and Eli Lilly have both made limited licensing arrangements to allow generic production of semaglutide and tirzepatide in certain lower-income countries, but those arrangements cover a small fraction of the global market. The WHO's review panel noted that the cost-effectiveness analyses available, mostly conducted in high-income country settings, consistently find these drugs cost-effective when accounting for cardiovascular benefit and diabetes prevention, but that this calculation does not translate into access for most of the world's obese population.

What the WHO is expected to recommend

Based on the reviews, the WHO's updated guidance is expected to recommend GLP-1 drugs as a treatment option for adults with obesity and at least one weight-related comorbidity, such as type 2 diabetes, hypertension, or established cardiovascular disease. The guidance is not expected to recommend them as a first-line standalone treatment or for cosmetic weight loss in people without metabolic complications. The WHO will also likely address the chronic use question, framing the expectation that treatment should be ongoing rather than time-limited, which has cost implications for any national health system considering public coverage.

The updated WHO obesity treatment guidance is scheduled for consultation with member states in the third quarter of 2025, with final publication expected in the fourth quarter. Several national health technology assessment bodies, including the UK's NICE and Germany's IQWiG, are expected to reference the WHO guidance in their own coverage decisions on tirzepatide, which is currently under evaluation for NHS coverage with a decision anticipated in late 2025.