Insulin: The Century-Old Drug That Still Shapes Modern Diabetes Care

By: Dr. Nima Mehran | MD

This article is for educational purposes only. Always consult your healthcare provider before starting or changing any medication.

Quick Hits

• Rapid-acting insulins: lispro (Humalog), aspart (Novolog), glulisine (Apidra). Fast onset (~15 minutes), used at mealtimes.

• Short-acting insulin: regular human insulin (Humulin R, Novolin R). Slower than rapid-acting; sometimes used in hospitals.

• Intermediate-acting insulin: NPH (Humulin N, Novolin N). Developed in the 1940s, peaks mid-day, still used in low-cost regimens.

• Long-acting insulins: glargine (Lantus, Basaglar, Toujeo), detemir (Levemir). Provide 24-hour “basal” coverage.

• Ultra-long-acting: degludec (Tresiba). Lasts up to 42 hours, offers flexibility.

• Premixed insulins: blends of intermediate + rapid/short (70/30, 75/25). Convenient, but rigid schedules.

• Delivery innovations: insulin pens, pumps, closed-loop “artificial pancreas” systems, and inhaled insulin (Afrezza).

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Insulin: The Drug That Saved Millions

A century ago, type 1 diabetes was a death sentence. Children diagnosed rarely survived more than a year or two, wasting away as their bodies starved despite food. Then in 1921, in a modest lab in Toronto, Frederick Banting and Charles Best isolated insulin from a dog’s pancreas. By 1922, a 14-year-old boy named Leonard Thompson, frail and near death, received the first insulin injection. Within days, he was sitting up, smiling, and eating.

That moment didn’t just change one boy’s life, it changed medicine forever.

Today, insulin is one of the most prescribed, most essential drugs in the world. Nearly 8.4 million Americans use insulin to manage type 1 diabetes, advanced type 2 diabetes, or gestational diabetes. Despite newer drugs and technologies, insulin remains the backbone of diabetes care.

Yet insulin is not one drug but a family of medications, engineered over decades to better mimic the body’s natural rhythms. From the first crude animal extracts to modern designer analogs and smart delivery systems, insulin’s story is one of both scientific triumph and human struggle, including debates about cost and access.

Rapid-Acting Insulins: Mimicking Nature’s Mealtime Spike

When you eat, your pancreas normally releases a burst of insulin to shuttle glucose into cells. In diabetes, that mealtime surge has to be replaced.

Enter rapid-acting insulins like lispro (Humalog), aspart (Novolog), and glulisine (Apidra). Engineered in the 1990s, these analogs kick in within 15 minutes, peak in an hour, and fade within 4 hours.

Why it matters: This speed allows patients to take insulin just before meals, matching their blood sugar rise. It’s a far cry from the older regular insulin, which forced patients to plan meals 30–45 minutes in advance.

Everyday life: A 22-year-old college student with type 1 diabetes can use an insulin pump filled with aspart. The pump delivers tiny continuous doses, plus mealtime “boluses.” With it, she has the freedom to eat pizza at midnight or skip breakfast without as much fear of a glucose rollercoaster.

Caveat: Rapid-acting insulins require careful carb counting and monitoring. If meals are skipped or delayed, hypoglycemia (dangerously low blood sugar) can occur.

Short-Acting Insulin: The Old Workhorse

Before the analog revolution, regular human insulin (Humulin R, Novolin R) was the standard mealtime insulin. It’s slower, kicking in after 30 minutes and lasting up to 8 hours.

Why it’s still around:

• Cheaper than newer analogs.

• Hospitals rely on it for IV infusions to control blood sugar in critically ill patients.

• In resource-limited settings, it remains the mainstay.

But in daily life, its slower onset means patients must plan meals in advance, a burden in today’s fast-paced world.

Intermediate-Acting Insulin: NPH and the 1940s Breakthrough

In 1946, scientists added a protein (protamine) to insulin, creating NPH (Neutral Protamine Hagedorn) insulin. For the first time, insulin could last 12–18 hours, reducing the need for multiple daily injections.

Today’s role:

• Still widely used globally, especially where cost is an issue.

• In the U.S., it’s sometimes used for gestational diabetes or in combination with short-acting insulins.

Drawback: NPH has a pronounced peak 4–12 hours after injection. If meals don’t match that curve, blood sugar can crash. For many patients, this unpredictability has been replaced by smoother long-acting insulins.

Long-Acting Insulins: Smoothing the Basal Line

The 1990s brought a revolution: long-acting insulin analogs designed to provide a flat, 24-hour background level of insulin, much like a healthy pancreas does between meals.

• Glargine (Lantus, Basaglar, Toujeo): The first “basal” analog, releasing steadily for about 24 hours. Toujeo is a concentrated form lasting a bit longer.

• Detemir (Levemir): Another long-acting option, sometimes requiring twice-daily dosing but predictable and steady.

Impact: Long-acting insulins reduced nighttime hypoglycemia and simplified regimens. Instead of juggling NPH peaks, patients could take a once-daily injection and not worry about timing meals so rigidly.

Real-world story: A 60-year-old man with type 2 diabetes struggling on pills is started on glargine at bedtime. His morning sugars stabilize, his A1C drops, and he avoids the dangerous lows he had on NPH.

Ultra-Long-Acting Insulin: Freedom in Flexibility

Insulin degludec (Tresiba), introduced in the 2010s, pushed boundaries further. With a half-life over 25 hours, it provides stable coverage for up to 42 hours.

Why it’s different: Patients no longer have to take insulin at the exact same time every day. Miss a morning shot? Take it in the evening. Travel across time zones? Adjust without chaos.

Evidence: Trials show degludec reduces hypoglycemia episodes compared to glargine, making it a favorite for those with unpredictable schedules, from night-shift nurses to frequent travelers.

Premixed Insulins: Convenience at a Cost

For patients who want fewer daily injections, premixed insulins combine rapid- or short-acting insulin with intermediate insulin in fixed ratios (like 70/30 or 75/25).

Pros:

• Two-in-one shot simplifies regimens.

• Useful for patients with consistent meal schedules.

Cons:

• Less flexible, insulin peaks may not match irregular eating habits.

• Harder to adjust one component without affecting the other.

Beyond the Needle: New Delivery Systems

For decades, insulin meant vials and syringes. Today, options abound:

• Pens: Disposable or refillable, with easy dose dialing and less stigma.

• Pumps: Continuous infusion of rapid-acting insulin, paired with “boluses” for meals.

• Closed-loop systems (“artificial pancreas”): umps linked to continuous glucose monitors (CGMs) that automatically adjust insulin, a major step toward automated care.

• Inhaled insulin (Afrezza): A needle-free powder inhaled before meals. Fast-acting, though not suitable for people with lung disease.

Safety: The Double-Edged Sword

Hypoglycemia: The most feared side effect. Too much insulin, too little food, or too much activity can send glucose plummeting. Symptoms include shakiness, sweating, confusion, and — in severe cases — seizures or coma.

Weight gain: As insulin helps the body store glucose, weight gain is common, especially in type 2 diabetes.

Injection site issues: Repeated use of the same spot can cause lumps (lipohypertrophy), affecting absorption.

Despite these concerns, insulin remains one of the most effective, life-sustaining drugs ever created.

The Future: Smart Insulins and Beyond

Researchers are developing “smart insulins” that activate only when blood sugar rises, reducing hypoglycemia risk. Others are working on once-weekly insulin injections and improved closed-loop systems that act almost like a natural pancreas.

Yet even as technology advances, insulin affordability remains a pressing issue. In the U.S., high prices have forced some patients to ration doses, with tragic consequences. Efforts are underway to cap insulin costs and expand access to generics and biosimilars.

Popular Insulins at a Glance

Insulin: Old Medicine, Ever-New

Insulin is both a 100-year-old discovery and a modern marvel. It turned a fatal disease into a manageable condition, saving millions of lives. Over the decades, scientists have refined it into faster, longer, smoother versions — and built delivery systems that give patients more freedom.

But at its core, insulin remains what it has always been: a lifeline. For patients with diabetes, it is not just a drug but a daily companion, sometimes frustrating, sometimes empowering, but always essential.

Sources

American Diabetes Association. Standards of Medical Care in Diabetes—2024. Diabetes Care, vol. 47, suppl. 1, 2024, pp. S1–S210.

Bliss, Michael. The Discovery of Insulin. University of Chicago Press, 1982.

Centers for Disease Control and Prevention (CDC). Insulin Therapy for Diabetes. CDC, 2023, www.cdc.gov/diabetes/diabetesmedications/insulin.html.

Heise, Tim, and Lutz Heinemann. “Insulin Therapy: Current and Future Trends.” Diabetes Care, vol. 44, no. 2, 2021, pp. 398–407.

Hirsch, Irl B., and Matthew C. Riddle. Insulin Therapy in Diabetes. American Diabetes Association, 2021.

Nathan, David M., et al. “Management of Hyperglycemia in Type 2 Diabetes: A Consensus Report by the American Diabetes Association and the European Association for the Study of Diabetes.” Diabetes Care, vol. 46, no. 9, 2023, pp. 2129–2145.

Rodbard, David. “The Evolving Role of Insulin Therapy in Type 2 Diabetes.” Postgraduate Medicine, vol. 131, no. 4, 2019, pp. 251–263.