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GLP-1 Drugs in 2025: Expanding Risks and Unexpected Benefits

Executive Summary

GLP-1 drugs like Ozempic and Wegovy dominated medical headlines in 2025 as researchers uncovered a surprisingly broad range of both safety concerns and unexpected benefits beyond their original diabetes and weight-loss indications. The worrying safety signals included potential eye problems (a blinding condition called NAION), dental issues dubbed "Ozempic teeth," hair loss in women, and complications in specific populations like pregnant women and lung transplant recipients. On the flip side, these drugs showed promise for conditions nobody expected—from reducing fracture risk and certain cancers to helping with fibromyalgia pain, rheumatoid arthritis, skin conditions, alcohol addiction, and even lowering death rates in dialysis patients.

Article Link: https://www.medpagetoday.com/endocrinology/obesity/119252

Author & Institution

Author: Kristen Monaco, Senior Staff Writer at MedPage Today (focusing on endocrinology, psychiatry, and nephrology news)

Institution: MedPage Today (medical news publication)

Conflicts of Interest: None apparent—this is a journalistic review article, not industry-sponsored research

The Data: What We Learned in 2025

This article reviews approximately 15-20 different studies published throughout 2025, ranging from small cohort studies to massive observational analyses involving hundreds of thousands to millions of patients.

Strengths

  • Comprehensive scope: Reviews data from nearly 2 million veterans initially, then tracks developments across multiple large studies throughout the year, giving a broad view of real-world use.
  • Large sample sizes: Many studies involved 350,000+ patients, which helps detect rare side effects that smaller trials might miss.
  • Real-world data: Most studies used observational data from actual clinical practice rather than controlled trials, showing what happens when regular doctors prescribe these drugs to regular patients.
  • Diverse outcomes examined: Researchers looked beyond the obvious diabetes and weight metrics to investigate everything from bone health to cancer to psychiatric conditions, revealing unexpected effects.
  • Comparative effectiveness: Studies often compared GLP-1 drugs to other diabetes medications (DPP-4 inhibitors, SGLT2 inhibitors), which helps isolate the specific effects of GLP-1s rather than just comparing to nothing.

Weaknesses

  • Observational study limitations: None of these are randomized controlled trials, so we can't prove causation—people who get prescribed GLP-1 drugs might be different from those who don't in ways we can't measure.
  • Surveillance bias concerns: The article mentions that increased thyroid cancer risk might just be because doctors are watching GLP-1 users more carefully and finding cancers they would have missed otherwise—this same bias could affect other findings.
  • Mechanism mystery: The article doesn't explain WHY these drugs would affect so many different body systems (eyes, bones, immune system, brain), making it hard to know if these are real effects or statistical noise.
  • Conflicting signals: Some findings seem contradictory—pregnant women had more preeclampsia but less preterm delivery, for example—making it tough to know the net benefit or harm.
  • Short follow-up: Most studies tracked patients for 1-2 years maximum, but people might take these drugs for decades, so we don't know about long-term effects.
  • Missing control for confounders: People who can afford or access GLP-1 drugs might be wealthier, have better healthcare, or be more health-conscious, which could explain some of the benefits unrelated to the drug itself.
  • Publication bias risk: We're probably seeing more published studies showing positive effects (cancer reduction, bone protection) than negative ones because journals prefer exciting findings.

Evidence Summary Table

Potential Benefits

OutcomeStudy Type/ReferenceData Strength Commentary
Reduced fracture risk (vertebral, hip, wrist)350,000-person observational study over 2 years<sup>[11,12]</sup>Moderate-Strong: Very large sample size and multiple fracture types examined; however, observational design can't rule out that GLP-1 users simply have better bone health to begin with
Lower cancer risk (12 of 13 obesity-related cancers plus lung)Large retrospective study; 17% lower overall risk<sup>[13]</sup>Moderate: Large numbers but retrospective design; could be confounded by weight loss itself or healthier behaviors in GLP-1 users
Reduced obesity-related cancer risk vs. DPP-4 inhibitorsTarget trial emulation (HR 0.93)<sup>[14]</sup>Moderate-Strong: Target trial emulation is sophisticated observational method that mimics randomized trials; head-to-head comparison strengthens findings
Improved fibromyalgia symptoms (less pain, fatigue, opioid use)Analysis of medical records<sup>[15]</sup>Weak-Moderate: Observational records; fibromyalgia symptoms are subjective and could be influenced by weight loss or other factors
Rheumatoid arthritis disease improvementSmall study: 32% improved vs. 17% in non-starters<sup>[16]</sup>Weak: Small sample size and comparing users to "prescribed but didn't start" creates selection bias
Better hidradenitis suppurativa outcomesSmall study over 6 months<sup>[17]</sup>Weak-Moderate: Small sample and short duration; unclear if benefits are from weight loss or direct drug effect
10% lower depression risk vs. DPP-4 inhibitorsTarget trial emulation of Medicare data<sup>[18]</sup>Moderate-Strong: Large Medicare dataset and sophisticated analysis method; reassuring psychiatric safety signal
Lower epilepsy risk in diabetes patientsStudy mentioned (link provided in article)<sup>[19]</sup>Unknown: Insufficient detail in summary article to assess
Benefits in asthma and cardiopulmonary conditionsReal-world data study<sup>[20]</sup>Moderate: Real-world data helpful but mechanism unclear—could be weight-related
Potential for alcohol addiction treatmentClinical trial<sup>[21]</sup>Moderate-Strong: Actual trial (not just observational) is encouraging, but details not provided
Reduced risk of GI conditionsStudy mentioned<sup>[22]</sup>Unknown: Insufficient detail to assess
Lower risk of death in dialysis patientsObservational study<sup>[23]</sup>Moderate: Highly relevant to nephrology but observational; dialysis patients taking GLP-1s may be healthier overall
Possible reduced uveitis riskStudy mentioned<sup>[24]</sup>Unknown: Insufficient detail to assess

Potential Risks and Side Effects

Adverse EffectStudy Type/ReferenceData Strength Commentary
NAION (potentially blinding eye condition) - 4x higher risk initially2024 report followed by 2025 data showing smaller risk<sup>[2,3,4]</sup>Moderate: European Medicines Agency issued warning; signal persists across multiple analyses but risk magnitude uncertain; FDA monitoring but no official warning yet
Dental problems ("Ozempic teeth") - periodontal disease, decayExpert opinion/mechanistic hypothesis<sup>[5]</sup>Weak: Based on known side effect (dry mouth) and theoretical mechanism; no controlled studies; anecdotal reports only
Hair loss in women (2x higher risk vs. bupropion-naltrexone)16 million patient study plus clinical trial reports<sup>[7]</sup>Moderate-Strong: Very large observational study confirmed by clinical trial data; gender-specific finding (not seen in men) strengthens signal
Thyroid cancer (85% higher risk in first year)350,000-person analysis in 2025<sup>[6]</sup>Weak-Moderate: Large study but researchers suggest surveillance bias; most GLP-1s carry black box warning already; timing (first year spike) suggests detection bias
Pregnancy complications (preeclampsia, HELLP syndrome, eclampsia)Large observational study, February 2025<sup>[8]</sup>Moderate: Large sample but complicated by fact that preterm delivery was lower; unclear if net benefit or harm
Preterm deliverySame pregnancy study<sup>[8]</sup>Protective effect: Lower preterm delivery despite other complications creates confusing picture
Antibody-mediated rejection in lung transplant recipients (15-fold higher odds)Small cohort study: 34 GLP-1 users among 301 transplants<sup>[9]</sup>Moderate: Small numbers but extremely high odds ratio is alarming for this specific population; mechanistically plausible given immune effects
Chronic cough lasting >8 weeks (12% higher risk)Chronic cough investigation<sup>[10]</sup>Moderate: Signal persisted even after removing GERD patients; large enough study to detect but mechanism unclear
Frequent vomiting (known class effect)Established side effect mentioned re: dental damage<sup>[5]</sup>Strong: Well-documented class effect from clinical trials

References

  1. Initial observational study of nearly 2 million U.S. military veterans showing broad spectrum of possible risks and benefits associated with GLP-1 receptor agonists (January 2025, referenced in article introduction)
  2. European Medicines Agency warning about non-arteritic anterior ischemic optic neuropathy (NAION) potentially caused by semaglutide (2025)
  3. 2024 report linking semaglutide with fourfold higher risk for NAION
  4. Follow-up data in 2025 showing smaller NAION risks than previously reported
  5. Expert opinions and mechanistic hypotheses regarding "Ozempic teeth" - periodontal disease, tooth decay, and bad breath associated with GLP-1 drugs via dry mouth and vomiting-related gastric acid erosion
  6. 350,000-person analysis examining thyroid cancer risk in adults with type 2 diabetes on GLP-1 agents (2025) - reported 85% higher thyroid cancer risk within first year compared with SGLT2 inhibitors, DPP-4 inhibitors, or sulfonylureas
  7. Preprint study of 16 million patients examining hair loss risk - found women who newly initiated semaglutide had twofold higher risk of hair loss compared to bupropion-naltrexone users; men did not have increased risk
  8. Large observational study of pregnant women with type 2 diabetes using semaglutide (February 2025) - examined preeclampsia, HELLP syndrome, eclampsia, and preterm delivery outcomes
  9. Small cohort study of 301 consecutive lung transplants examining antibody-mediated rejection risk (April 2025) - 34 patients taking GLP-1 agents had 15-fold greater adjusted odds of antibody-mediated rejection
  10. Chronic cough investigation examining adults prescribed GLP-1 agonist for type 2 diabetes - found 12% higher risk for new chronic cough lasting >8 weeks versus those prescribed another second-line anti-diabetic medication
  11. Observational report showing GLP-1 receptor agonist users with type 2 diabetes had small but significant reductions in 10-year chances of vertebral fractures (1.5% vs 1.8% for nonusers)
  12. Study of 350,000 GLP-1 agonist users finding significantly lower risk for multiple fracture types (vertebral wedge compression, subtrochanteric, intertrochanteric, femoral neck, distal radius, periprosthetic) after 2 years compared with women with diabetes who did not use these agents
  13. Large retrospective study reporting 17% lower overall cancer risk with GLP-1 agonist use versus non-users - showed lower incidence for 12 of 13 recognized obesity-related cancers plus lung cancer
  14. Target trial emulation study examining obesity-related cancer risk - GLP-1 agonist users with type 2 diabetes and obesity had lower risk (HR 0.93) compared with DPP-4 inhibitor users
  15. Analysis of medical records showing GLP-1 receptor agonist users with fibromyalgia were less likely to use opioids or report pain, fatigue, and malaise versus non-users
  16. Small study of patients with rheumatoid arthritis on GLP-1 drugs for obesity - 32% had disease activity improvement after 1 year compared with 17% of patients prescribed but never starting the drugs
  17. Small study of patients with hidradenitis suppurativa on GLP-1 agents - within 6 months, patients were significantly more likely to experience ≥1-point reduction in global assessment scores, fewer disease flares, and improved quality of life
  18. Target trial emulation of Medicare data (February 2025) - older adults with diabetes who used GLP-1 agonists had 10% lower risk for depression compared with DPP-4 inhibitor users
  19. Study: "GLP-1 Drugs Linked to Lower Epilepsy Risk in Diabetes Patients" (referenced in article)
  20. Study: "Real-World Data Back GLP-1s in Asthma, Cardiopulmonary Conditions" (referenced in article)
  21. Clinical trial: "Ozempic Shows Potential for Alcohol Addiction in Trial" (referenced in article)
  22. Study: "GLP-1 Drugs May Cut Risk of Pesky GI Condition" (referenced in article)
  23. Study: "GLP-1 Agonists Tied to Lower Risk of Death in Dialysis Patients" (referenced in article)
  24. Study: "Another Win for GLP-1 Agonists? A Possible Reduced Risk of Uveitis" (referenced in article)

Note: This is a journalistic review article by MedPage Today summarizing multiple studies from 2025. Complete citations for individual studies were not provided in the original article. References 19-24 are titles of linked articles within the MedPage Today piece but without full study details.

Bottom Line for Dinner Table Discussion

The GLP-1 story in 2025 shows us that blockbuster drugs often have effects we never anticipated—both good and bad. While doctors and patients focus on weight loss and blood sugar, these drugs appear to be doing something fundamental throughout the body that we still don't fully understand. The American Medical Association even proposed creating a special registry to track side effects, though it hasn't happened yet. The challenge is that most of this data comes from observational studies—researchers watching what happens rather than running controlled experiments—so it's hard to know which associations are real and which are coincidental. For now, the safety signals warrant caution in certain populations (pregnant women, lung transplant patients), while the unexpected benefits need confirmation through more rigorous testing before anyone should take these drugs specifically for conditions like fibromyalgia or cancer prevention.

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