Peptide education
Semaglutide
Also known as: GLP-1 receptor agonist — Glucagon-like peptide-1 (GLP-1) receptor agonist
Semaglutide is the outlier on this list: a peptide with large, published randomized trials and regulatory approval — for specific indications, under prescription. Its inclusion illustrates what real evidence looks like.
Regulatory status
FDA-approved for specific indications (type 2 diabetes; chronic weight management under defined criteria) — by prescription only. Compounded and gray-market versions are a separate, FDA-warned category.
What the evidence shows
STEP 1 (NEJM 2021) showed ~14.9% mean weight loss over 68 weeks versus 2.4% with placebo. SUSTAIN-6 demonstrated cardiovascular safety signals in type 2 diabetes. Efficacy and adverse-event profiles are well characterized within approved use.
Human evidence
Multiple large phase-III RCTs; post-marketing surveillance ongoing.
Animal & preclinical evidence
Full regulatory preclinical package; rodent thyroid C-cell tumor signal drives a boxed warning.
Proposed mechanism
Agonizes GLP-1 receptors: enhances glucose-dependent insulin secretion, suppresses glucagon, delays gastric emptying, and reduces appetite via central pathways.
Potential risks
- GI adverse events (nausea, vomiting) are common
- Boxed warning: thyroid C-cell tumors in rodents — contraindicated with relevant history
- Gallbladder events and pancreatitis reports
- Compounded/gray-market versions carry dosing and purity risks the approved product does not
Contraindications
- Personal/family history of medullary thyroid carcinoma or MEN 2
- History of pancreatitis (caution)
- Pregnancy
Common research endpoints
- Body weight change vs placebo
- HbA1c reduction
- Major adverse cardiovascular events
Questions to ask a licensed clinician
- Do I meet the approved criteria for prescription?
- What is the plan for GI side-effect management and dose titration?
- What happens to weight and metabolic markers on discontinuation?
- Why should I avoid compounded or gray-market versions?
References
- Wilding JPH, Batterham RL, Calanna S, et al. (2021). Once-weekly semaglutide in adults with overweight or obesity (STEP 1). New England Journal of Medicine. SourcePhase-III RCT
- Marso SP, Bain SC, Consoli A, et al. (2016). Semaglutide and cardiovascular outcomes in patients with type 2 diabetes (SUSTAIN-6). New England Journal of Medicine. SourcePhase-III RCT
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