Decoding 'The Big 3 Drugs'
The phrase 'the big 3 drugs' does not have a single, official definition in pharmacology. Its meaning is context-dependent and can refer to various groupings based on different metrics. In some contexts, it refers to specific antibiotic cocktails or drugs used in anti-doping [1.2.2, 1.2.3]. However, the most common interpretations focus on market and clinical impact. This article explores the top three drugs through three critical lenses: global sales revenue, the number of prescriptions written, and their historical, field-defining significance.
The Titans of Revenue: Best-Selling Drugs Worldwide
When measuring by financial success, the 'big 3' are dominated by highly specialized, often biologic, medications that command high prices. As of early 2025 data, these drugs generate tens of billions in annual sales.
1. Keytruda (pembrolizumab)
Keytruda is a revolutionary immunotherapy drug used to treat numerous types of cancer, including melanoma, lung cancer, head and neck cancer, and triple-negative breast cancer [1.6.3, 1.6.5]. With 2024 sales reaching approximately $29.5 billion, it stands as a giant in the pharmaceutical market [1.4.5].
- Mechanism of Action: Keytruda is a PD-1 inhibitor. It works by blocking the PD-1 pathway, which cancer cells often exploit to hide from the body's immune system. By blocking this pathway, Keytruda helps T-cells (a type of immune cell) to recognize and attack cancer cells [1.6.1, 1.6.2].
- Primary Uses: It is approved for a wide and growing list of cancers, often used for advanced or metastatic disease, and sometimes in earlier stages to prevent recurrence [1.6.1, 1.6.6].
2. Eliquis (apixaban)
Eliquis is a top-selling anticoagulant (blood thinner) with 2024 sales around $20.7 billion [1.4.5]. Its widespread use is driven by the need to prevent serious cardiovascular events in large patient populations.
- Mechanism of Action: Eliquis is a direct Factor Xa inhibitor. It works by blocking Factor Xa, a key protein in the blood clotting process (the clotting cascade). This action makes the blood less likely to form dangerous clots [1.8.1, 1.8.3, 1.8.5].
- Primary Uses: It is prescribed to reduce the risk of stroke in people with nonvalvular atrial fibrillation (AFib), treat and prevent deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevent DVT after hip or knee replacement surgery [1.8.4].
3. Ozempic (semaglutide)
Ozempic, a GLP-1 receptor agonist, has seen a meteoric rise, with 2024 sales hitting approximately $18.6 billion [1.4.5]. While approved for diabetes, its profound weight loss effects have driven massive demand.
- Mechanism of Action: Ozempic mimics a natural hormone called GLP-1. It stimulates insulin secretion in a glucose-dependent manner, lowers glucagon secretion, and slows gastric emptying. It also acts on brain centers to reduce appetite and increase feelings of fullness [1.7.2, 1.7.5].
- Primary Uses: Its primary FDA-approved indication is to improve glycemic control in adults with type 2 diabetes and to reduce the risk of major adverse cardiovascular events in those with established heart disease [1.7.3]. Its off-label use for weight loss is also widespread, with sister drug Wegovy (a higher dose of semaglutide) being approved for chronic weight management [1.7.1, 1.7.3].
The Workhorses: Most-Prescribed Drugs
The most-prescribed drugs are typically affordable, generic medications used to manage common, chronic conditions affecting millions of people, such as high cholesterol, high blood pressure, and hypothyroidism.
1. Atorvastatin (Lipitor)
With over 112 million prescriptions in one year, Atorvastatin is a dominant force in managing cholesterol [1.3.1]. It is used as a primary and secondary preventive measure against cardiovascular diseases [1.9.2].
- Mechanism of Action: As a statin, it works by inhibiting HMG-CoA reductase, an enzyme crucial for cholesterol synthesis in the liver. This reduces overall cholesterol levels in the bloodstream [1.9.2].
- Primary Uses: It is used to manage high cholesterol (hyperlipidemia), and to reduce the risk of stroke and heart attack in patients with risk factors like diabetes or a history of cardiovascular events [1.9.1].
2. Levothyroxine (Synthroid)
This medication is used to treat hypothyroidism (underactive thyroid), a condition where the thyroid gland doesn't produce enough thyroid hormone. It is the second most prescribed drug, with over 102 million prescriptions annually [1.3.1].
- Mechanism of Action: Levothyroxine is a synthetic version of the thyroxine (T4) hormone. It replaces the hormone that the thyroid is unable to produce, helping to regulate the body's energy and metabolism [1.3.1].
- Primary Uses: Its main use is treating hypothyroidism. It is also used to treat or prevent goiter (an enlarged thyroid gland) [1.3.1].
3. Lisinopril (Prinivil, Zestril)
As a widely used treatment for high blood pressure, Lisinopril accounts for nearly 92 million prescriptions per year [1.3.1].
- Mechanism of Action: It is an ACE (angiotensin-converting enzyme) inhibitor. It works by blocking the production of angiotensin II, a substance that narrows blood vessels. This relaxes the blood vessels, which lowers blood pressure and makes it easier for the heart to pump blood [1.3.1].
- Primary Uses: Primarily used to treat high blood pressure (hypertension), it is also used for heart failure and to improve survival after a heart attack [1.3.1, 1.3.6].
Comparison Table: Revenue Titans vs. Prescription Workhorses
| Drug (Brand Name) | Primary Use | Metric of Dominance | Mechanism of Action |
|---|---|---|---|
| Keytruda | Cancer (various types) | ~$29.5 Billion Sales (2024) [1.4.5] | PD-1 Inhibitor (Immunotherapy) [1.6.2] |
| Eliquis | Blood Clot Prevention/Treatment | ~$20.7 Billion Sales (2024) [1.4.5] | Factor Xa Inhibitor [1.8.1] |
| Ozempic | Type 2 Diabetes | ~$18.6 Billion Sales (2024) [1.4.5] | GLP-1 Receptor Agonist [1.7.2] |
| Atorvastatin | High Cholesterol | ~112 Million Prescriptions/Year [1.3.1] | HMG-CoA Reductase Inhibitor (Statin) [1.9.2] |
| Levothyroxine | Hypothyroidism | ~102 Million Prescriptions/Year [1.3.1] | Synthetic Thyroid Hormone [1.3.1] |
| Lisinopril | High Blood Pressure | ~92 Million Prescriptions/Year [1.3.1] | ACE Inhibitor [1.3.1] |
Pillars of Medicine: Historically Significant Drugs
A third interpretation of 'the big 3' involves drugs that fundamentally changed medicine and public health.
- Penicillin: Discovered in 1928, Penicillin was the first true antibiotic [1.5.5]. Its introduction started the antibiotic era, transforming the treatment of bacterial infections and saving countless lives from conditions that were once death sentences [1.5.6].
- Aspirin (Salicylic Acid): Derived from willow bark in the 19th century, aspirin is one of the most widely used drugs in history [1.5.4]. It is a foundational non-steroidal anti-inflammatory drug (NSAID) used for pain, fever, and inflammation, and its later discovery as an antiplatelet agent made it a staple for cardiovascular disease prevention.
- Morphine: Isolated from the opium poppy, morphine provided a powerful and reliable method for pain relief, revolutionizing surgery and palliative care [1.5.4]. It became the gold standard for treating severe pain and the progenitor for a vast class of opioid analgesics.
Conclusion
So, 'What are the big 3 drugs?' The answer is a mosaic. From a financial perspective, Keytruda, Eliquis, and Ozempic are the modern titans, reflecting innovation in oncology, cardiology, and metabolic disease. From a daily healthcare perspective, Atorvastatin, Levothyroxine, and Lisinopril are the indispensable workhorses, managing the chronic conditions of millions. And from a historical viewpoint, Penicillin, Aspirin, and Morphine are the foundational pillars upon which much of modern pharmacology was built. Each group of three tells a different but equally important story about medicine.
For further reading on drug development and discovery, a valuable resource is the National Center for Biotechnology Information (NCBI).
