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Stack • Goal: Sustained weight reduction

Modern Fat Loss Stack

The two incretin-based therapies driving the modern weight-loss revolution — semaglutide as the accessible default, tirzepatide as the higher-efficacy option.

Duration
12+ months
Experience
beginner

Peptides in this stack

This isn't really a "stack"

Unlike research-peptide stacks where compounds are combined, the fat-loss decision is either/or. You pick one GLP-1 agent and titrate it. Combining GLP-1 drugs is not clinically validated and significantly increases GI side-effect risk.

Choosing between them

FactorSemaglutide (Wegovy)Tirzepatide (Mounjaro)
Mean weight loss~15% over 68 weeks~20% over 72 weeks
Head-to-headBaselineSuperior in SURMOUNT-5
UK NHS accessTightly controlledExpanded 2025
Private cost£150–£250/month£150–£200/month
MechanismGLP-1 onlyDual GIP/GLP-1

For most people starting out, tirzepatide is the rational choice given superior efficacy at similar cost and tolerability. Semaglutide remains a strong option for those already stable on it or where supply is an issue.

What comes next

  • Retatrutide (Phase 3): triple agonist with ~24% weight loss in Phase 2. Expected approval 2027+.
  • Oral GLP-1s: Rybelsus (oral semaglutide) exists but has much lower bioavailability. Orforglipron is a non-peptide oral GLP-1 in late-stage development.

Practical considerations

  • Plan for 4–6 months of titration to reach therapeutic dose.
  • GI side effects are worst during titration and usually settle.
  • Discontinuation without lifestyle change leads to weight regain — plan for long-term use or a structured taper with dietary and resistance-training support.
  • Lean mass preservation matters: pair with adequate protein (≥1.6 g/kg) and resistance training.