GLP-1//GUIDE

GLP-1 (glucagon-like peptide-1) is an incretin hormone released by the gut after eating. The medications mimic this signal at supra-physiological doses, producing four overlapping effects.

• Appetite suppression: central action on the hypothalamus reduces hunger and food noise
• Slowed gastric emptying: fullness lasts longer after meals, reducing intake
• Improved insulin response: better glucose control, reduced post-meal spikes
• Reward modulation: lower drive toward hyperpalatable foods and alcohol

Two molecules dominate clinical use. Both are weekly subcutaneous injections. Tirzepatide is generally more effective for weight loss; semaglutide has the longer track record.

Side effects are dose-dependent and largely avoidable with patient titration. The schedules below are FDA-approved starting points; many clinicians slow them further.

1. 1Semaglutide: 0.25mg weekly for 4 weeks → 0.5mg → 1.0mg → 1.7mg → 2.4mg. Increase only when current dose is well-tolerated.
2. 2Tirzepatide: 2.5mg weekly for 4 weeks → 5mg → 7.5mg → 10mg → 12.5mg → 15mg. Many people plateau effectively at 7.5–10mg.
3. 3Hold the dose: If side effects are intolerable or weight loss is steady, there is no requirement to keep escalating.
4. 4Re-titrate if interrupted: After a break of more than 2 weeks, drop back at least one step to avoid GI rebound.

Most side effects are GI and resolve within days of dose changes. The severe events (pancreatitis, gallbladder disease) are rare but real — know the warning signs.

• Nausea: Eat smaller meals, avoid high-fat foods, hydrate aggressively. Resolves in 1–2 weeks at each new dose.
• Constipation: Fiber (psyllium 5–10g/day), magnesium citrate, 2.5L water minimum.
• Fatigue: Often a calorie deficit symptom. Verify protein intake and electrolytes before blaming the drug.
• Loss of muscle: Up to 40% of weight lost can be lean mass without intervention. Resistance training + protein is non-negotiable.

The single biggest mistake on GLP-1s is treating them as a passive weight-loss tool. Without resistance training and adequate protein, you lose muscle, your metabolic rate drops, and the rebound is brutal.

1. 1Protein: 1.6–2.2g per kg of goal body weight. This is the floor, not the ceiling. Whey or casein when appetite fails.
2. 2Resistance training: 3–4 sessions per week. Compound lifts. Heavy enough to drive adaptation (RPE 7–9).
3. 3Steps: 8,000–10,000 daily. NEAT collapses on aggressive deficits — walking is the cheapest defense.
4. 4Creatine: 5g daily. One of the most evidence-backed muscle-sparing supplements during a deficit.

Run baseline labs before starting and recheck at 3 and 6 months. GLP-1s improve most metabolic markers but can mask developing issues.

Most people regain weight after stopping if no behavioral system was built. Treat the medication window as the time to install the operating system.

• Build the habit stack first: Training, protein, sleep, step count — these must be automatic before you taper.
• Taper slowly: Drop one step every 4–8 weeks rather than stopping cold.
• Maintenance dosing: Many do well at the lowest effective dose long-term — this is a valid strategy.
• Plan for 5–10% rebound: Some regain is normal. The system catches it before it compounds.