GLP-1 Therapies Newsletter
Issue #39June 1, 20267 studies

Semaglutide linked to reduced cigarette craving in 24 smokers

GLP-1 drugs like semaglutide and tirzepatide are making headlines for dramatic weight loss. But this week's research reveals these medications might have effects far beyond the scale—from helping smokers quit to protecting hearts and kidneys in ways scientists are still figuring out.

🚬 Semaglutide May Help Smokers Quit Without Trying

  • 24 daily smokers received 9 weeks of semaglutide (building up to 1.0 mg) or placebo in a controlled trial
  • Semaglutide significantly reduced cigarette craving compared to placebo, though it didn't increase lab-measured smoking resistance or reduce weekly cigarette consumption
  • Participants weren't trying to quit—they were recruited as "non-treatment-seeking" smokers who used at least 5 cigarettes daily

Why it matters: This suggests semaglutide might reduce nicotine addiction even when people aren't actively trying to quit smoking, potentially opening new pathways for smoking cessation treatment.

🥈 Top 2% journal 🔗 JAMA network open Randomized Controlled Trial 🗓️ May 26

Key Findings

🏥 Tirzepatide Beats Semaglutide for Extreme Weight Loss

  • Network analysis of 25 trials involving 12 different obesity medications found tirzepatide 15 mg produced the greatest weight reduction at 17.97%
  • For patients achieving ≥20% weight loss, CagriSema (a combination drug) showed the strongest effect with 27.82 times higher odds than placebo, followed by tirzepatide 15 mg at 23.70 times higher odds
  • Gastrointestinal side effects increased across all treatments, but serious adverse events remained comparable to placebo
💡 Dual-pathway drugs like tirzepatide may represent the new gold standard for patients needing substantial weight loss.
Top 20% journal 🔗 Endocrinology, diabetes & metabolism Network Meta-Analysis 🗓️ May 28

❤️ Semaglutide Cuts Death Risk Across 39,000 Patients

  • Meta-analysis of 8 trials with 39,204 patients found semaglutide reduced all-cause mortality by 16% and cardiovascular death by 17%
  • Major heart attacks dropped by 25%, and worsening heart failure decreased by 16% compared to placebo
  • Benefits extended to kidney outcomes, with an 17% reduction in kidney disease progression
💡 Semaglutide appears to protect multiple organ systems simultaneously, not just aid weight loss.
🥈 Top 2% journal 🔗 Cardiovascular diabetology Journal Article 🗓️ May 26

🧠 GLP-1 Drugs May Fight Addiction Beyond Food

  • Comprehensive review of preclinical studies shows GLP-1 receptor agonists consistently reduced intake and seeking behaviors for alcohol, nicotine, opioids, and stimulants
  • Early clinical trials revealed therapeutic potential for reducing alcohol use and supporting smoking cessation
  • Effects appear to work through modulation of brain reward pathways, specifically mesolimbic dopamine signaling
💡 These medications might help treat multiple addictions by targeting shared brain reward circuits.
Top 20% journal 🔗 Pharmacology, biochemistry, and behavior Review 🗓️ May 25

⚖️ Muscle Loss Emerges as Key Concern

  • Analysis of 43 trials with 3,379 participants found GLP-1 drugs substantially reduced total body fat, visceral fat, and liver fat
  • High-dose versions (liraglutide 1.8 mg daily, semaglutide 1.0 mg weekly, tirzepatide 15 mg weekly) significantly decreased lean muscle mass
  • No significant differences in total lean tissue percentage were observed, suggesting the muscle loss may be proportional to overall weight reduction
💡 The muscle-preserving effects of these drugs may depend heavily on dosage and individual patient factors.
🔗 Diabetes, obesity & metabolism Journal Article 🗓️ May 28

👁️ Eye Condition Risk Linked to Semaglutide

  • Meta-analysis of 8 studies covering over 14 million participants found semaglutide users had 3.36 times higher risk of developing NAION (a form of sudden vision loss) at 1-year follow-up
  • Risk remained elevated at 2.37 times higher even after 5 years of use in patients with type 2 diabetes
  • NAION is a rare but serious condition that can cause permanent vision loss in one eye
💡 This rare but serious eye complication may require monitoring in long-term semaglutide users.
Top 20% journal 🔗 Graefes Arch Clin Exp Ophthalmol Review 🗓️ May 27

🤰 Pregnancy Risks Emerge from Real-World Data

  • Study of 429 pregnant women exposed to semaglutide found 2.88 times higher odds of excessive weight gain during pregnancy compared to non-users
  • Risk of gestational diabetes increased by 59%, and cesarean delivery risk jumped 3.35 times higher
  • Former users who stopped before pregnancy showed similar risks, suggesting rebound effects rather than direct drug toxicity
💡 Stopping semaglutide before pregnancy may not eliminate risks, pointing to complex metabolic rebound effects.
🥉 Top 5% journal 🔗 Obstetrics and gynecology Journal Article 🗓️ May 28

Implications

This week's research reveals GLP-1 drugs are far more than weight-loss medications—they're emerging as multi-system therapies that may help with addiction, protect hearts and kidneys, but also carry previously unknown risks. The challenge now is understanding how to maximize benefits while managing side effects like muscle loss and rare complications.

Studies in this issue

Primary sources used for this newsletter.

  1. Weekly Semaglutide treatment in adults who smoke daily: A randomized clinical trial
    main storyJAMA network open2026-05-26PMID 42189538
  2. Semaglutide and the risk of sudden optic nerve damage in type 2 diabetes: A systematic review and meta-analysis
    key findingGraefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie2026-05-27PMID 42201355
  3. Comparing the Effects of CagriSegma, Semaglutide, Cagrilintide, and Tirzepatide for Treating Overweight and Obesity
    key findingEndocrinology, diabetes & metabolism2026-05-28PMID 42207966
  4. Body Composition Changes Linked to Different GLP-1 Medications in Overweight or Obese Adults With or Without Type 2 Diabetes
    key findingDiabetes, obesity & metabolism2026-05-28PMID 42209204
  5. Semaglutide's impact on death rates, heart, and kidney health across related metabolic conditions
    key findingCardiovascular diabetology2026-05-26PMID 42186086
  6. How GLP-1 receptor drugs relate to both obesity and addiction: shared brain mechanisms and evidence from research
    key findingPharmacology, biochemistry, and behavior2026-05-25PMID 42184906
  7. Weight Gain During Pregnancy and Birth Results After Taking Semaglutide
    key findingObstetrics and gynecology2026-05-28PMID 42208070

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