GLP-1s Preserving Muscle with Training

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GLP-1 receptor agonists (e.g., semaglutide branded as Ozempic or Wegovy, tirzepatide branded as Mounjaro or Zepbound) are injectable drugs that mimic the gut hormone GLP-1 to slow digestion, blunt hunger, and improve blood sugar control (Wikipedia contributors, 2025a). Originally designed for type 2 diabetes, they exploded in popularity when clinical trials showed 15–25% average weight loss, far surpassing most diet or lifestyle programs (PubMed, 2024). This “Hollywood drug” reputation made them a cultural phenomenon—fueled by celebrity stories, TikTok testimonials, and mainstream media hype (Los Angeles Times; People.com).

But popularity has downsides. Off-label use for mild vanity weight loss, compounded “gray market” injections (often mislabeled or overdosed), and micro-dosing hacks shared online are increasingly common (FDA; Verywell Health, 2025). Some users push doses higher than indicated, hoping for faster fat loss, while others cut pens into dozens of “microdoses” to save money—both practices raise safety concerns (People.com, 2025). The result is a widening gap between how these drugs are meant to be used under supervision, and how they’re actually being used in gyms, clinics, and home bathrooms worldwide.

• Weight & body-comp: Semaglutide and tirzepatide produce large fat loss; lean mass typically falls ~20–40% of total weight lost without countermeasures (Neeland, 2024; Rodríguez-Jiménez, 2024; Look, 2025; Ramos, 2025).
   
• Head-to-head, real-world: Tirzepatide tends to outperform semaglutide for weight loss (L.A. Times, 2025).
   
• Doses (on-label): Wegovy starts 0.25 mg weekly → step up to 1.7–2.4 mg; Zepbound starts 2.5 mg weekly → step up to 5/10/15 mg (2.5 mg is not a maintenance dose) (FDA labels).
   
• Compounded/micro-dosing risks: FDA has flagged dosing errors (5–20× overdoses) and counterfeit compounded products; shortages eased in 2025, so compounding crackdowns followed (FDA; People.com).
   
• Muscle preservation: Target ~1.6 g/kg/day protein and 20–40 g protein within ~2 h post-training; prioritize progressive resistance training (Morton, 2018; Schoenfeld, 2018; Wilkinson, 2023).
   
• Practical training guidance: PT groups and clinical orgs emphasize strength first while on GLP-1s (Hinge Health).
   

1. Zepbound (2.5→5 mg, ~5–8 weeks): 20 lb in a month, minimal side effects beyond constipation. Appetite control improved at 5 mg. (WebMD Zepbound, Aug 2025).
    
2. Zepbound (2.5 mg, ~2 months): ~12 lb loss; no nausea; planned increase to 5 mg when appetite returned. (WebMD, Jan 2025).
    
3. Zepbound (maintenance, ~9 months): 103 lb loss, only complaint hair loss. (WebMD, Jul 2025).
    
4. Zepbound (5→7.5→10 mg, age 72): Broke plateau at 10 mg; learned trigger foods. (WebMD, Jul 2025).
    
5. Zepbound (2.5→7.5 mg, 3.5 months): ~20 lb loss; better sleep; mild hair thinning early. (WebMD, Jun 2025).
    
6. Mounjaro (2.5→15 mg, 10 months): 115 lb loss; nausea only at start; very structured diet. (Drugs.com).
    
7. Mounjaro (2.5 mg, 2 months): ~40 lb loss at lowest dose; appetite vanished. (Drugs.com).
    
8. Mounjaro (5 mg, 3 months, T2D): A1C 8.4→5.9, 30 lb loss, minimal side effects. (WebMD, May 2025).
    
9. Ozempic (0.25→1.0 mg, 9 months): 40 lb loss, A1C 8.1→5.6; early nausea faded. (Drugs.com).
    
10. Ozempic (0.25 mg, 12 weeks): 24 lb loss with gym + Noom; didn’t increase dose. (WebMD).
     

1. Zepbound (first shot): Severe diarrhea/nausea, wanted lower dose. (WebMD).
    
2. Zepbound (10→15 mg): Severe nausea/diarrhea, hypotension episode. (WebMD).
    
3. Zepbound (2.5 mg, first week): Nausea, headache, fatigue. (WebMD).
    
4. Mounjaro (~10 weeks): Hospitalized for paralytic ileus (rare). (Drugs.com).
    
5. Mounjaro (weight loss use): Vomiting/diarrhea, dizziness after shot; rapid weight drop but intolerable. (WebMD).
    
6. Ozempic (0.25 mg single dose): ER visit; sulfur burps, nonstop vomiting/diarrhea. (Drugs.com).
    
7. Ozempic (first week): “Sick as a dog,” chills/nausea; discontinued. (Drugs.com).
    
8. Ozempic (0.5 mg, 2 months): Daily vomiting, dehydration, back pain; lost 30 lb but miserable. (Drugs.com).
    
9. Ozempic (1.0 mg): Severe constipation weekly requiring laxatives. (Drugs.com).
    
10. Ozempic (long-term): Non-responder; weight gain, anemia, heart concerns. (WebMD).
     

Pattern: Success = right dose + gradual titration + diet/exercise; failures = too-rapid dose jumps, GI intolerance, lack of nutrition support, or counterfeit/compounded sources.

• Wegovy® (semaglutide): 0.25 mg for 4 wks → 0.5 → 1.0 → 1.7 → 2.4 mg maintenance. (FDA label).
   
• Zepbound® (tirzepatide): Start 2.5 mg for 4 wks → 5/7.5/10/12.5/15 mg. (FDA label).
   
• Why differences? Diabetes control often achieved at lower doses; maximal weight loss requires higher. Some stop at lower doses if satiety is adequate. GI-sensitive patients may titrate slower. Microdosing trends (0.05–0.125 mg semaglutide) lack evidence and pose safety risks (Verywell Health, 2025).
   

• Strength training 2–4×/week with progressive overload (Hinge Health, 2025).
   
• Protein target: ~1.6 g/kg/day, with 20–40 g within 2 h post-training (Morton et al., 2018; Schoenfeld et al., 2018).
   
• Expect some lean mass loss (25–30% of total weight lost) but fight it with resistance training, adequate calories, hydration, and sleep (Neeland, 2024; Ramos, 2025).
   

• Stick to FDA-approved pens; avoid compounding/counterfeits (FDA alert, 2025).
   
• Stop if severe abdominal pain, vomiting, or dehydration persists; seek medical evaluation for gallbladder, pancreatitis, or rare ileus risks (Drugs.com reports).
   
• Plan for maintenance phase: stopping GLP-1s often leads to regain unless lifestyle changes or lower-dose maintenance are in place (Frontiers in Endocrinology, 2024).