GLP-1 receptor agonist

Semaglutide

A once-weekly GLP-1 receptor agonist that slows gastric emptying, improves insulin sensitivity, and quiets the appetite signaling centers in the brain.

Category: Weight loss Used in: Semaglutide · Wegovy®

How it works

Semaglutide is a long-acting analog of human glucagon-like peptide-1 (GLP-1). It binds the GLP-1 receptor on pancreatic β-cells (boosting glucose-dependent insulin secretion), in the gut (slowing gastric emptying), and in hypothalamic appetite centers (reducing hunger and 'food noise').

The evidence

The STEP 1 trial (2021, NEJM) reported an average ~14.9% body weight reduction at 68 weeks in non-diabetic adults on weekly semaglutide 2.4 mg vs. ~2.4% with placebo. The SELECT trial (2023) demonstrated a 20% reduction in major adverse cardiovascular events in overweight/obese patients with established cardiovascular disease. These trials studied the FDA-approved branded products that contain this molecule (Wegovy, Ozempic); compounded semaglutide is prepared by 503A pharmacies, is not FDA-approved, and was not the subject of these trials.

Typical dosing

Standard titration: 0.25 mg weekly subcutaneous injection for 4 weeks, doubling every 4 weeks (0.5 → 1.0 → 1.7 → 2.4 mg) as tolerated. Most members reach a maintenance dose between 1.0 mg and 2.4 mg weekly.

Side effects

Common

  • Nausea
  • Constipation
  • Diarrhea
  • Fatigue (early titration)
  • Reduced appetite

Less common

  • Acid reflux
  • Injection-site reactions
  • Gallbladder discomfort

Rare

  • Pancreatitis
  • Acute kidney injury (dehydration-related)

Drug interactions

  • Insulin and sulfonylureas — increased hypoglycemia risk; doses may need reduction
  • Oral medications with narrow therapeutic windows — slowed absorption due to delayed gastric emptying
  • Combined GLP-1 / GIP agonists (e.g. tirzepatide) — never co-administer

Frequently asked

Which products contain semaglutide?
Semaglutide is the active molecule in several FDA-approved products: Ozempic (type 2 diabetes), Wegovy (chronic weight management), and Rybelsus (oral). Compounded semaglutide is prepared by 503A pharmacies; it is not FDA-approved and is not an FDA-approved generic or equivalent of those branded products.
How long until results?
Appetite suppression begins within 1–2 weeks. Weight changes typically start at week 4–8 with steady titration.
Can I stop and restart?
Yes, but plan around your titration. Resuming at full dose after a long gap will reproduce early-titration side effects.

References

  1. STEP 1 — Wilding et al., NEJM 2021 (n=1,961): −14.9% mean body weight at week 68 vs −2.4% placebo
  2. SELECT — Lincoff et al., NEJM 2023 (n=17,604): 20% relative reduction in major adverse cardiovascular events
  3. STEP 4 — Rubino et al., JAMA 2021: weight regain after discontinuation vs continued treatment