Semaglutide

Overview

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist developed by Novo Nordisk. It is a synthetic analogue of the human GLP-1 hormone, modified for a long half-life so it can be dosed once weekly. It was first approved for type 2 diabetes in 2017 under the brand name Ozempic (injection) and Rybelsus (oral tablet), and in 2021 for chronic weight management under the brand name Wegovy.

Two structural modifications give semaglutide its durability: an amino-acid substitution at position 8 (Aib8) that resists DPP-4 enzymatic breakdown, and a C18 fatty-diacid chain that binds tightly to albumin in the blood, slowing kidney clearance. The result is a circulating half-life of roughly one week. Semaglutide is one of the most extensively studied peptides in modern medicine, with large randomised cardiovascular and weight-loss outcome trials.

Approved & studied uses

Semaglutide has approved indications as well as a growing body of trial evidence in adjacent areas:

• Type 2 diabetes: improves glycaemic control (HbA1c reduction); approved as Ozempic and Rybelsus.
• Chronic weight management: approved as Wegovy for adults with obesity, or overweight with a weight-related condition.
• Cardiovascular risk reduction: the SELECT trial showed reduced major adverse cardiovascular events in people with established cardiovascular disease and obesity.
• Metabolic-associated fatty liver disease (MASH/NAFLD): improvement in liver histology in phase II trials.
• Chronic kidney disease: the FLOW trial reported slowed kidney-disease progression in type 2 diabetes.
• Emerging research: studied for addiction, polycystic ovary syndrome, and neurodegenerative endpoints.

Beyond approved use, semaglutide is widely obtained through compounding pharmacies and “research” suppliers. Those products are not FDA-reviewed for purity or potency and fall outside the approved supply chain.

Mechanism of action

Semaglutide activates the GLP-1 receptor, reproducing and prolonging the effects of the body’s natural incretin response. Its actions span several systems:

• Glucose-dependent insulin secretion: stimulates the pancreas to release insulin only when blood glucose is elevated, lowering the risk of hypoglycaemia relative to insulin itself.
• Glucagon suppression: reduces glucagon output from the pancreas, decreasing hepatic glucose production.
• Delayed gastric emptying: slows the rate at which food leaves the stomach, prolonging fullness after meals.
• Central appetite regulation: acts on GLP-1 receptors in the hypothalamus and hindbrain to reduce hunger and food reward, lowering overall energy intake.

The combination of reduced appetite and slowed gastric emptying drives the weight-loss effect, while the insulin/glucagon actions account for glycaemic control. The fatty-acid/albumin-binding modification is what extends these effects across a full week.

Protocols

Quick Reference

Syringe units assume a compounded 10 mg vial reconstituted with 2 mL BAC water (5 mg/mL) drawn in a 1 mL / 100-unit insulin syringe. Approved pens (Ozempic/Wegovy) come pre-filled and pre-dosed.

Titration schedule

Semaglutide follows one standard escalating schedule: start low, step up every 4 weeks, then hold at the maintenance dose. This limits nausea while the body adapts. Units assume the 10 mg / 2 mL vial above (5 mg/mL).

Standard weight-loss titration (STEP trials ↗). For type-2 diabetes the maintenance target is typically 1–2 mg weekly (FDA label ↗); some clinicians hold at a conservative 1 mg for tolerability.

Administration Routes

Semaglutide is delivered subcutaneously once weekly, or as a daily oral tablet in a separate approved formulation.

Reconstitution Guide

Approved pens are pre-filled and require no mixing. The steps below apply only to compounded lyophilised semaglutide supplied as a powder. New to this? See Peptides 101 for the fundamentals.

Reconstitution Calculator

Enter your vial size, water volume, and intended dose to calculate the exact volume and syringe markings. Defaults to the 0.25 mg starting dose.

Active compound & chemistry

Semaglutide is a 31-amino-acid peptide analogue of human GLP-1 (7–37), sharing about 94% sequence homology with the native hormone. Its molecular formula is C₁₈₇H₂₉₁N₄₅O₅₉ and the molecular weight is approximately 4114 Da. Two engineered modifications define it: substitution of alanine at position 8 with α-aminoisobutyric acid (Aib8), which blocks degradation by the DPP-4 enzyme, and attachment of a C18 fatty-diacid chain via a γGlu-2×OEG linker, which drives strong, reversible binding to serum albumin.

That albumin binding reduces renal clearance and gives semaglutide its ~165-hour (roughly one-week) half-life, enabling once-weekly dosing. Look up the compound in PubChem for full structural data, canonical SMILES, and InChI.

Evidence summary

Semaglutide is supported by an unusually strong, independent evidence base for a peptide: multiple large randomised controlled trials with hard clinical endpoints.

Warnings & cautions

• Boxed warning: thyroid C-cell tumours. Semaglutide caused thyroid C-cell tumours in rodents. It is contraindicated in anyone with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
• Pancreatitis. Acute and necrotising pancreatitis have been reported. Stop use and seek care for severe, persistent abdominal pain.
• Gastrointestinal effects. Nausea, vomiting, diarrhoea, and constipation are common, especially during dose escalation. Severe cases include ileus and gastroparesis.
• Gallbladder disease & hypoglycaemia. Increased risk of gallstones; hypoglycaemia risk rises when combined with insulin or sulfonylureas.
• Not for type 1 diabetes or diabetic ketoacidosis. Use in pregnancy is not recommended.
• Compounded / “research” source quality is uncontrolled. Products sold outside the approved pharmacy supply chain are not FDA-verified for identity, purity, or dose.