GLP-1 Therapies Newsletter
Issue #38May 25, 20267 studies
Two-thirds of patients kept weight off after stopping GLP-1 drugs
New research is painting a more nuanced picture of what happens when people stop taking GLP-1 drugs like Ozempic and Wegovy. While weight regain has been a major concern, real-world data suggests the story isn't as simple as "stop the drug, gain it all back."
🔬 Most Patients Don't Regain Weight After Stopping GLP-1 Drugs
- 4,182 patients were tracked for 6 months after their last semaglutide or tirzepatide prescription
- Two-thirds of patients showed stable weight or continued weight loss during this period
- Among 119 patients who actually discontinued treatment (rather than just having gaps in prescriptions), 72% didn't demonstrate weight regain
Why it matters: This challenges the assumption that stopping GLP-1 drugs inevitably leads to rapid weight regain, suggesting some patients may maintain benefits even after discontinuation.
Key Findings
🎯 Super Responders Lose 20+ Years of Weight
- Analysis of 135,349 patients found "super responders" (>15% weight loss) had the highest rates with Zepbound (34%), followed by Wegovy (26%)
- Super responders' average weight after 1 year was similar to their weight from 20 years prior to treatment
- These patients were more likely to be younger (51 vs 55 years), female (80% vs 58-65%), and white (90% vs 80%)
💡 Identifying who becomes a super responder could help personalize GLP-1 treatment strategies.
💊 Combination Therapy Beats Solo Treatment for Kidney Disease
- 120 patients with early diabetic kidney disease were randomized to canagliflozin, semaglutide, combination therapy, or placebo for 24 weeks
- Combination therapy achieved significantly greater reductions in protein in urine compared to either drug alone
- All treatment groups showed better metabolic control and reduced inflammation markers compared to placebo
💡 Combining different diabetes drugs may provide superior kidney protection than using either medication alone.
🧠 GLP-1 Drugs Show Promise for Alcohol Use Disorder
- Review of 13 preclinical studies, 14 clinical studies, and 4 published trials found convergent evidence that GLP-1 drugs reduce alcohol consumption
- 19 additional interventional trials are currently in progress or completed but unpublished
- Both animal and human studies consistently showed improved alcohol-related outcomes
💡 GLP-1 drugs may offer a new treatment avenue for alcohol addiction, expanding their therapeutic potential beyond diabetes and obesity.
⚠️ Real-World Persistence Remains Low
- Among 393 patients starting semaglutide for weight loss, only 44% remained persistent at 12 months
- Persistent patients lost 13.8% of baseline weight compared to 6.4% for non-persistent patients
- Female patients had lower odds of persistence (OR = 0.32) and adherence (OR = 0.33) compared to males
💡 Less than half of patients stick with GLP-1 treatment for a full year, highlighting the need for better support strategies.
🫀 Liraglutide May Reduce Atrial Fibrillation Risk
- Meta-analysis of 6 major cardiovascular outcome trials found a pooled risk ratio of 0.87 for atrial fibrillation events with GLP-1 drugs
- AF events were infrequent (0.2%-1.2%) across studies and detected through adverse event reporting
- The direction of effect was consistent across all trials, though not statistically significant
💡 GLP-1 drugs may contribute to heart rhythm benefits, though dedicated studies with systematic monitoring are needed to confirm this.
🧪 Semaglutide May Slow Biological Aging
- 84 adults with HIV-associated lipohypertrophy were randomized to semaglutide or placebo for 32 weeks
- Semaglutide reduced epigenetic aging across multiple measures, including PhenoAge (-4.9 years), GrimAge V2 (-2.3 years), and DunedinPACE (9% slower aging)
- Effects were seen in inflammation, brain, and heart aging measures
💡 GLP-1 drugs might have anti-aging effects beyond weight loss, though larger studies are needed to confirm this potential.
Implications
This week's research reveals GLP-1 drugs are more complex than initially thought. While persistence remains challenging and not everyone responds dramatically, these medications may offer benefits that extend well beyond weight loss—from addiction treatment to heart rhythm protection to potentially slowing aging itself. The key seems to be identifying who will respond best and providing adequate support for those who do.
Studies in this issue
Primary sources used for this newsletter.
- Weight changes after the last prescription of tirzepatide or semaglutide across a health networkmain storyBiology methods & protocols2026-05-21PMID 42163990
- Using GLP-1 Receptor Drugs to Treat Alcohol Use Disorder: A Critical Reviewkey findingAlcohol, clinical & experimental research2026-05-18PMID 42144979
- Semaglutide may slow biological aging in people with HIV-related fat buildupkey findingNature communications2026-05-19PMID 42156721
- Using semaglutide to treat obesity in everyday healthcare: a group studykey findingJournal of managed care & specialty pharmacy2026-05-21PMID 42166306
- Short-term effects of semaglutide alone or with canagliflozin on early diabetic kidney diseasekey findingPakistan journal of pharmaceutical sciences2026-05-22PMID 42170981
- Link Between GLP-1 Receptor Agonist Medications and Risk of Atrial Fibrillation: Review and Analysis of Clinical Trialskey findingCureus2026-05-19PMID 42153045
- Understanding key traits of people who respond best to GLP-1RA weight-loss treatmentkey findingBiology methods & protocols2026-05-18PMID 42147968
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