Ultimate Longevity Bible

Intervention

GLP-1 Agonists (Semaglutide, Tirzepatide, Liraglutide)

Last updated Sun May 17 2026 00:00:00 GMT+0000 (Coordinated Universal Time)

What they are

GLP-1 receptor agonists mimic the gut incretin hormone GLP-1. The incretin-class drugs in widest use:

  • Liraglutide (Saxenda, Victoza) — daily injection.
  • Semaglutide (Ozempic, Wegovy, Rybelsus) — weekly injection or oral.
  • Tirzepatide (Mounjaro, Zepbound) — weekly injection; dual GLP-1 + GIP agonist.
  • Retatrutide (in development) — triple GLP-1/GIP/glucagon agonist.

Why they matter for longevity

  • Weight loss: 15–25% body weight reduction sustained over months in obese populations.
  • Cardiovascular events: SELECT trial showed semaglutide reduced major adverse cardiovascular events by 20% in obese non-diabetics.
  • Kidney outcomes: FLOW trial showed kidney-event reduction in T2D with diabetic kidney disease.
  • Cognition: signals for reduced Alzheimer’s incidence in observational data; RCTs underway.
  • Substance use: emerging evidence for reduced cravings (alcohol, nicotine, opioids).

Mechanism

  • Slows gastric emptying → satiety.
  • Acts on hypothalamic appetite centres.
  • Enhances glucose-dependent insulin secretion.
  • Anti-inflammatory effects in vascular endothelium.

Safety

GI side effects (nausea, vomiting) are common at start. Rare but documented: pancreatitis, gallstone disease, increased pulse rate. Black-box warning for thyroid C-cell tumors (rodent data; uncertain in humans). Significant loss of lean mass alongside fat — resistance training matters here.

Related entries

Type 2 diabetes, Cardiovascular disease, SELECT trial.

References

  • Lincoff, A. M. et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). N. Engl. J. Med. 389, 2221–2232 (2023).

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