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Metabolic

Semaglutide

Also known as Ozempic, Wegovy, Rybelsus (oral form), Sema

Semaglutide is a long-acting GLP-1 receptor agonist studied for type 2 diabetes glycemic control, chronic weight management, and cardiovascular risk reduction.

Molecular weight4113.58 g/mol
Half-life~165 hours (about 7 days)
CategoryMetabolic

Typical use cases

✓ Type 2 diabetes glycemic control✓ Chronic weight management / obesity✓ Appetite and food-craving reduction✓ Cardiovascular risk reduction in established CVD with overweight/obesity✓ Metabolic syndrome and insulin-resistance support✓ Investigational use in MASH/NAFLD (fatty liver)

Dosing guidelines

StartingCommonly reported in research/community protocols: 0.25 mg subcutaneously once weekly as an introductory/tolerance-building step.
MaintenanceCommonly reported maintenance ranges: 0.5-2 mg once weekly for glycemic-focused use; up to 2.4 mg once weekly for weight-management-focused protocols.
Max (studied)Highest commonly reported weekly dose is 2.4 mg subcutaneously (weight-management protocols); 2 mg in glycemic-focused protocols.

Titration

Protocols commonly describe a stepwise monthly escalation to limit gastrointestinal effects, e.g. ~4 weeks each at 0.25 mg, then 0.5 mg, then 1 mg, then 1.7 mg, then 2.4 mg once weekly. Steps are typically held longer if side effects are pronounced. Educational only; not a dosing instruction.

Reconstitution

Approved pens (Ozempic/Wegovy) are pre-filled liquid solutions requiring NO reconstitution. Lyophilized research-grade powder is commonly reconstituted with bacteriostatic 0.9% sodium chloride or sterile water; the volume is chosen to give a convenient concentration (e.g. 2 mg powder in 1 mL yields 2 mg/mL). Swirl gently rather than shaking.

Injection sites

Subcutaneous injection into the abdomen, thigh, or upper arm; sites are rotated each week.

Storage & handling

Refrigerate at 2-8 C (36-46 F); protect from light and do not freeze. Approved pens may be kept at room temperature (up to ~30 C / 86 F) for a limited in-use window (about 28-56 days depending on product). Reconstituted research-grade solution is typically refrigerated and used within a few weeks.

Side effects

  • Nausea Mild · Common
  • Vomiting and diarrhea Moderate · Common
  • Constipation and abdominal discomfort Mild · Common
  • Delayed gastric emptying / gastroparesis-like effects Moderate · Uncommon
  • Acute pancreatitis Severe · Rare
  • Gallbladder disease (cholelithiasis/cholecystitis) Moderate · Uncommon

Research summary

Semaglutide is among the most rigorously studied GLP-1 receptor agonists, supported by an extensive human evidence base spanning the SUSTAIN program (type 2 diabetes), the STEP program (obesity/weight management), and the SELECT cardiovascular-outcomes trial. It is a 94%-homologous analogue of native human GLP-1, modified at position 8 to resist DPP-4 degradation and acylated with a C18 fatty di-acid that promotes albumin binding, yielding a half-life near 1 week. In the STEP 1 trial, once-weekly 2.4 mg subcutaneous semaglutide produced roughly 15% mean body-weight reduction in adults with overweight or obesity without diabetes, far exceeding placebo. The SELECT trial (17,604 adults with established cardiovascular disease, overweight/obesity, no diabetes) reported a roughly 20% reduction in major adverse cardiovascular events, with prespecified analyses suggesting cardioprotection partly independent of weight loss. Long-term SELECT follow-up showed weight reduction sustained to roughly 4 years and signals of kidney benefit. Limitations include high rates of gastrointestinal adverse events, frequent weight regain after discontinuation, a rodent thyroid C-cell tumor signal of uncertain human relevance, and limited very-long-term safety data; oral semaglutide formulations exist but have markedly lower, food-sensitive bioavailability. Compounded and research-grade ("gray market") semaglutide is widely used outside approved channels, where potency, purity, and sterility are not guaranteed.

Key references

  • https://pubchem.ncbi.nlm.nih.gov/compound/Semaglutide
  • https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=adec4fd2-6858-4c99-91d4-531f5f2a2d79
  • https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b
  • https://pmc.ncbi.nlm.nih.gov/articles/PMC8089593/
  • https://pmc.ncbi.nlm.nih.gov/articles/PMC11271387/
  • https://pmc.ncbi.nlm.nih.gov/articles/PMC8736331/

Related compounds

Tirzepatide → Liraglutide Retatrutide → Cagrilintide Dulaglutide Exenatide

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Educational reference only — not medical advice. Dosing figures are commonly-cited ranges, not prescriptions. Consult a qualified clinician.

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