GLP-1 Agonists
Glucagon-like peptide-1 receptor agonists for weight loss, metabolic optimization, and emerging anti-aging applications.
Evidence Summary
Robust RCT data for weight loss (15-20%) and diabetes. Cardiovascular benefits proven. Emerging evidence for NASH, addiction, and neurological conditions. Preclinical geroscience update (Sep 2026): in a peer-reviewed Nature study (Feng…Chen, 2 Sep 2026), semaglutide started at 20 months of age in female C57BL/6 mice extended median lifespan by ~12% (834 vs 742 days), improved endurance, spatial memory and glucose control, enhanced stem-cell regenerative capacity, and attenuated transcriptomic ageing hallmarks — recapitulating and in some domains exceeding matched calorie restriction. This is the first lifespan result for a GLP-1RA begun late in life. It is mouse-only, female-only and single-site; it does not establish a longevity effect in humans, where the only randomised ageing-biomarker signal to date is a ~9% slowing of PCGrimAge pace in a specific HIV-lipohypertrophy cohort (Nat Commun 2026).
Evidence Scale
Mechanism of Action
Mimics incretin hormone GLP-1, enhancing insulin secretion, suppressing glucagon, slowing gastric emptying, and reducing appetite through CNS effects.
Who Is This For?
Obesity, type 2 diabetes, metabolic syndrome, cardiovascular risk reduction. GI tolerance assessment.
Protocol & Dosing
Dose
Semaglutide: 0.25mg weekly, titrate to 1-2.4mg. Tirzepatide: 2.5mg weekly, titrate to 5-15mg.
Frequency
Weekly
Duration
Ongoing with monitoring
Protocol Summary
Weekly subcutaneous injection (semaglutide, tirzepatide) or daily oral. Titrate slowly to target dose.
Semaglutide vs. Orforglipron
Two paths to GLP-1 receptor activation — injectable peptide vs. oral small molecule.
| Semaglutide | Orforglipron Oral | |
|---|---|---|
| Class | GLP-1 receptor agonist (peptide) | Non-peptide GLP-1 receptor agonist (small molecule) |
| Route | Subcutaneous injection | Oral capsule |
| Typical dose | 0.25–2.4 mg weekly | 3 mg / 12 mg / 24 mg / 36 mg daily |
| Food restrictions | None | None (no fasting required) |
| Half-life | ~7 days | ~24 hours |
| Common use | Weight loss, T2D, cardiometabolic | Weight loss, glycemic control, T2D |
| Stage | FDA-approved (Ozempic / Wegovy) | FDA-approved (Foundayo) |
Oral GLP-1 (Orforglipron) — physician-vetted
Available in 3 mg and 12 mg capsules through BioXSciences, an independent third-party supplier.
Educational comparison only — not medical advice. Use under qualified physician supervision.
Interactions & Precautions
Contraindications
- Personal/family history of medullary thyroid cancer
- MEN2 syndrome
- Pancreatitis history
- Gastroparesis
Potential Risks
- •GI side effects
- •Muscle loss
- •Thyroid concerns (theoretical)
- •Cost
Potential Side Effects
Practitioner Notes
Clinical annotations from Dr. Goel
Protein intake critical to preserve muscle. Slow titration reduces GI effects. Consider cycling. Tirzepatide may be more effective. Monitor for muscle loss. Sep 2026: the Nature late-life mouse lifespan result (Feng…Chen) strengthens the calorie-restriction-mimetic rationale but should not be cited to patients as evidence that semaglutide extends human lifespan. Weigh against sarcopenia risk in older adults; body-composition monitoring and resistance training remain the priority. Watch the UTMB Moody tirzepatide-vs-epigenetic-clock trial and SURMOUNT-MMO for human ageing/mortality endpoints.
Dr. Sanjeev Goel
Chief Medical Officer, Peak Human
Cost & Access
Cost Range
$$$$
Accessibility
Availability varies by location
Sample member
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