What Is Semaglutide?

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist developed by Novo Nordisk. It mimics the effects of the naturally occurring incretin hormone GLP-1, which is released after eating and plays a crucial role in glucose metabolism and appetite regulation.

Type: GLP-1 receptor agonist Molecular Weight: 4,113.58 g/mol Half-life: ~7 days (allowing weekly dosing) Brand Names: Ozempic® (diabetes), Wegovy® (weight), Rybelsus® (oral) FDA Approval: 2017 (diabetes), 2021 (weight management)

Semaglutide has become one of the most significant pharmaceutical developments in metabolic medicine, with dramatic effects on both blood sugar control and body weight.

Key Characteristics

  • Administration: Weekly injection or daily oral tablet
  • Approved Uses: Type 2 diabetes, chronic weight management
  • Weight Loss: ~15-17% average in clinical trials
  • Mechanism: GLP-1 receptor agonist

Mechanism of Action

GLP-1 Receptor Activation

Semaglutide works by activating GLP-1 receptors throughout the body:

  • Pancreas: Enhances glucose-dependent insulin secretion
  • Brain: Reduces appetite and increases satiety
  • Stomach: Slows gastric emptying
  • Liver: Reduces glucose production

Blood Sugar Control

Multiple mechanisms improve glycemic control:

  • Stimulates insulin release when blood sugar is elevated
  • Suppresses glucagon secretion (glucose-dependent)
  • Slows carbohydrate absorption via delayed gastric emptying
  • Reduces hepatic glucose output

Weight Loss Mechanisms

Semaglutide induces weight loss through:

  • Reduced appetite and food cravings
  • Increased satiety (feeling full faster)
  • Delayed gastric emptying
  • Central nervous system effects on reward pathways

Clinical Trial Results

SUSTAIN Trials (Diabetes)

Trial Result HbA1c Reduction
SUSTAIN 1-6 Superior to comparators 1.5-1.8%
SUSTAIN 6 (CV outcomes) 26% reduction in CV events -

STEP Trials (Weight Management)

Trial Population Weight Loss
STEP 1 Obesity (no diabetes) -14.9% (vs -2.4% placebo)
STEP 2 Obesity with diabetes -9.6%
STEP 3 With intensive behavioral therapy -16.0%
STEP 4 Maintenance study Continued vs regain

SELECT Trial (Cardiovascular)

The SELECT trial (2023) demonstrated:

  • 20% reduction in major cardiovascular events
  • In patients with obesity but without diabetes
  • First GLP-1 to show CV benefit independent of diabetes

Approved Formulations

Semaglutide Products

  • Ozempic®: Weekly injection for type 2 diabetes (0.25mg, 0.5mg, 1mg, 2mg)
  • Wegovy®: Weekly injection for weight management (2.4mg)
  • Rybelsus®: Daily oral tablet for diabetes (3mg, 7mg, 14mg)

Side Effects

Common Side Effects

  • Nausea (most common, usually improves)
  • Vomiting
  • Diarrhea
  • Constipation
  • Abdominal pain
  • Headache

Serious Risks (Rare)

  • Pancreatitis
  • Gallbladder disease
  • Thyroid C-cell tumors (boxed warning; seen in rodents)
  • Hypoglycemia (when combined with insulin/sulfonylureas)
  • Acute kidney injury (from dehydration)

Contraindications

  • Personal/family history of medullary thyroid carcinoma
  • Multiple Endocrine Neoplasia syndrome type 2
  • History of pancreatitis (use with caution)

Ongoing Research

Active research areas for semaglutide:

  • NASH/Fatty liver: Trials showing liver fat reduction
  • Heart failure: STEP-HFpEF showing benefits
  • Kidney disease: FLOW trial results
  • Addiction: Early research in alcohol use disorder
  • Alzheimer's: EVOKE trials investigating cognitive effects

Key Published Research

Year Study Key Finding Journal
2016 SUSTAIN 6 Cardiovascular benefit in diabetes NEJM
2021 STEP 1 ~15% weight loss in obesity NEJM
2023 SELECT CV benefit in obesity without diabetes NEJM
2023 STEP-HFpEF Benefits in heart failure NEJM

Prescription Medication

Semaglutide (Ozempic, Wegovy, Rybelsus) is a prescription medication that should only be used under medical supervision. It is not available for research purchase. This information is for educational purposes about the science of GLP-1 agonists. Always consult healthcare providers for medical decisions.

Summary

Semaglutide represents a major advancement in metabolic medicine. Its dual approval for both diabetes and obesity, combined with proven cardiovascular benefits, has made it one of the most impactful medications in recent pharmaceutical history. The ongoing research into additional applications — from fatty liver to neurodegenerative diseases — suggests we're only beginning to understand the full potential of GLP-1 receptor agonism.

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