By Harshit
NEW YORK, November 17, 2025
The global surge in the use of GLP-1 receptor agonists—including tirzepatide (Mounjaro), semaglutide (Ozempic, Wegovy), and liraglutide (Saxenda)—has reshaped obesity treatment, offering weight-loss results previously unseen in modern medicine.
But as their popularity skyrockets, so do concerns about long-term safety, trial transparency, global equity, and the pharmaceutical influence behind most clinical evidence.
A trio of Cochrane Reviews, commissioned by the World Health Organization, offers the clearest independent assessment so far:
The drugs work — but major scientific and ethical questions remain unanswered.
GLP-1s: Proven Weight Loss Across Multiple Trials
Originally approved for type 2 diabetes, GLP-1 receptor agonists were known to lower blood sugar, reduce complications, aid weight loss, and lower mortality in high-risk diabetic patients. Their success prompted trials in people with obesity but without diabetes, leading to breakthrough findings.
The new reviews evaluated tirzepatide, semaglutide, and liraglutide across over 60,000 participants. Results were consistent and striking:
Tirzepatide
- ~16% body weight reduction in 12–18 months
- Data from 8 RCTs (6,361 people)
- Effects may persist up to 3.5 years
- Long-term safety remains unclear
Semaglutide
- ~11% weight loss over 24–68 weeks
- Based on 18 RCTs (27,949 people)
- Up to two years of sustained effect
- Higher rates of GI side effects (nausea, vomiting, diarrhea)
Liraglutide
- 4–5% weight loss
- Evidence from 24 RCTs (9,937 people)
- Data beyond two years is limited
Across all GLP-1 drugs:
- Major cardiovascular outcomes showed little to no difference versus placebo
- Quality-of-life measures changed minimally
- Gastrointestinal side effects were the most common cause of discontinuation
“These drugs have the potential to bring about substantial weight loss, particularly in the first year,” said Juan Franco, co-lead author from Heinrich Heine University Düsseldorf. “It’s an exciting moment after decades of unsuccessful attempts to treat obesity effectively.”
The Missing Pieces: Safety, Durability, and Who Benefits
1. Most Trials Are Funded by Drug Companies
A dominant concern across all reviews:
The majority of studies were funded, designed, or influenced by the pharmaceutical companies manufacturing the drugs.
This raises research transparency questions:
- choice of study populations
- handling of side effects
- selective reporting
- absence of long-term follow-up
Independent trials are now considered a major global priority.
2. Weight Regain After Stopping the Drugs
Early follow-up data shows:
- Most people regain a large portion of lost weight once they stop treatment
- Raises concerns about lifelong dependence
- Long-term metabolic and psychological impacts remain unknown
This could dramatically reshape obesity treatment strategies and insurance models worldwide.
3. Limited Long-Term Safety Data
The Cochrane assessments found:
- Insufficient evidence on long-term cardiovascular outcomes in low-risk individuals
- Little understanding of kidney, pancreas, gallbladder, or thyroid impacts over many years
- Uncertainty about rare side effects that may emerge only after widespread usage
“We need more data on long-term effects, particularly in lower-risk individuals,” said Eva Madrid, co-lead researcher from the University of Valparaíso, Chile.
4. High Costs Risk Widening Global Inequalities
Even where GLP-1 drugs are approved, cost is the biggest barrier.
- Semaglutide and tirzepatide can cost hundreds to over $1,000 per month
- Insurance often restricts coverage
- Liraglutide has become cheaper due to patent expiration, but is less effective
- Most trials were done in wealthy countries, leaving vast regions unstudied
Body composition, metabolism, diet, and disease patterns vary globally — meaning findings from Europe and the U.S. may not fully apply in Africa, South Asia, or Latin America.
Equitable access remains one of the WHO’s central concerns.
5. Who Should Receive GLP-1s? WHO Plans New Global Guidelines
With demand exploding, the WHO commissioned these evidence reviews to set global recommendations on:
- who should receive GLP-1s
- for how long
- at what BMI thresholds
- with what monitoring
- and at what cost
The upcoming guidelines aim to address:
- clinical safety
- ethical distribution
- cost-effectiveness
- population-based equity
“This is not just about weight,” one WHO official noted. “It’s about shaping global public health policy.”
Balancing Promise With Caution
GLP-1 drugs now represent one of the most promising advances in obesity treatment in decades.
But they also highlight a modern dilemma:
What happens when a powerful new medical technology is effective, expensive, and backed mostly by industry-funded science?
The Cochrane Reviews provide a balanced takeaway:
- The drugs work — often dramatically.
- Long-term consequences are still unknown.
- Access and affordability remain deeply inequitable.
- Independent research is essential.
- Public health decisions must consider societal impacts, not just individual weight loss.
The findings will now guide WHO’s global policy framework for obesity treatment — the first major international standard in the age of GLP-1 medicines.