Insulins
Long-Acting & Rapid-Acting — The Major Brands

Insulin has been keeping people with diabetes alive since 1922. For Type 1, it is non-negotiable. For Type 2, it represents a different story — one of a disease that progressed further than oral medications could manage, or a diagnosis that came in so late the pancreas was already severely depleted. Needing insulin as a T2D patient is not a failure. It is biology. Understanding which insulin does what — and what the real risks are — matters whether you’re starting it, managing it, or trying to avoid it through better control of the variables you can actually change.

Basal vs. Bolus — The Two Jobs Insulin Does

Basal insulin handles background glucose suppression. Your liver continuously releases glucose into the bloodstream between meals and overnight — a process called hepatic glucose output. Basal insulin suppresses this background release and keeps fasting glucose from climbing while you sleep or go hours without eating. Basal insulins are long-acting or ultra-long-acting — they are designed to provide a slow, steady, peakless release over 24–42 hours.

Bolus (mealtime) insulin handles the glucose spike from eating. Rapid-acting insulins are injected before or at the start of a meal and peak within 1–2 hours to match the absorption of carbohydrates. In a fully functioning pancreas, insulin is released in two phases — a rapid first-phase spike within minutes of eating, followed by a sustained second phase. Rapid-acting insulins approximate the first phase pharmacologically, though never perfectly.

Many T2D patients on insulin start with basal-only therapy — a single long-acting injection at night — which addresses elevated fasting glucose without requiring mealtime injections. As the disease progresses, bolus insulin may be added at one or more meals, transitioning to a full basal-bolus regimen.

The Long-Acting Insulins — Newest to Oldest

Tresiba — Insulin Degludec (2015)

Tresiba (Novo Nordisk), FDA-approved in September 2015, is an ultra-long-acting insulin with a duration of action exceeding 42 hours — the longest of any commercially available insulin. It forms a subcutaneous depot after injection and releases slowly into the circulation via gradual monomer dissociation. The practical advantages are significant: it has an extremely flat, peakless profile (lower hypoglycemia risk than Lantus in head-to-head trials), and its long half-life makes it forgiving of missed or delayed doses. If you forget your Tresiba and take it 8 hours late, the pharmacokinetics barely change. The DEVOTE trial (2017) showed Tresiba produced 40% fewer severe hypoglycemic events vs. insulin glargine U-100 (Lantus). Dosing: once daily, any time of day, dose can flex by up to 8 hours without clinical consequence. Available in U-100 and U-200 concentrations.

Toujeo — Insulin Glargine U-300 (2015)

Toujeo (Sanofi), FDA-approved in February 2015, is the same molecule as Lantus (insulin glargine) but at three times the concentration — 300 units/mL vs. 100 units/mL. Higher concentration means smaller injection volume, slower absorption from the subcutaneous depot, and a more extended, flatter action profile than standard glargine. Duration of action: approximately 36 hours. The EDITION trials showed Toujeo produced significantly fewer nocturnal hypoglycemia events compared to Lantus, particularly in the first 8 weeks of therapy. Dosing: once daily, same time each day. The pen is non-interchangeable with Lantus — the higher concentration means a unit of Toujeo and a unit of Lantus deliver the same amount of insulin, but the volume per dose is different. Patients switching between them require careful re-education to avoid dosing errors.

Basaglar — Insulin Glargine Biosimilar (2016)

Basaglar (Eli Lilly/Boehringer Ingelheim), approved in December 2015 and launched in 2016, was the first biosimilar insulin approved in the United States. It is biosimilar to Lantus — same active ingredient, same mechanism, same clinical profile, same dosing. It was priced approximately 15–20% below Lantus at launch. Semglee (Mylan/Viatris, 2020) is a second interchangeable biosimilar to Lantus and was the first insulin designated as interchangeable by the FDA — meaning pharmacists can substitute it for Lantus without physician authorization. These biosimilars have been the primary driver of price competition in the long-acting insulin market.

Lantus — Insulin Glargine U-100 (2000)

Lantus (Sanofi) was FDA-approved in April 2000 and became the most prescribed insulin in the world within a few years of launch. For nearly two decades, it was the reference standard for basal insulin. It works by forming microprecipitates under the skin at physiological pH, releasing insulin glargine slowly over approximately 24 hours with a relatively flat profile and no pronounced peak — a significant improvement over the NPH insulins it replaced, which peaked at 4–12 hours and caused predictable nocturnal hypoglycemia. Lantus is now available as a generic (insulin glargine injection, 100 units/mL) following patent expiry, and Sanofi itself caps Lantus list price. Standard dosing: once daily, same time each day; typical starting dose in T2D is 10 units or 0.1–0.2 units/kg, titrated upward.

The Rapid-Acting Insulins

Novolog — Insulin Aspart (2000) / Fiasp (2017)

Novolog (Novo Nordisk), FDA-approved in 2000, is a rapid-acting analog that begins working within 10–20 minutes of injection, peaks at 1–3 hours, and is out of the system by 3–5 hours. It is typically injected 5–10 minutes before eating. Fiasp (faster aspart, approved 2017) is a reformulated version with niacinamide added to accelerate initial absorption — onset in as little as 4 minutes — approved for dosing at the start of or within 20 minutes after a meal. Novolog is one of the two most prescribed rapid-acting insulins globally.

Humalog — Insulin Lispro (1996) / Lyumjev (2020)

Humalog (Eli Lilly), FDA-approved in 1996, was the first rapid-acting insulin analog — a milestone that ended the era of regular human insulin as the primary mealtime option. It has a nearly identical pharmacokinetic profile to Novolog (onset 15–30 min, peak 1–2 hours, duration 3–4 hours). Lyumjev (ultra-rapid lispro, 2020) is Lilly’s faster formulation, with onset under 15 minutes. Humalog has biosimilar competition from Admelog (Sanofi, 2017) and Civica/Mark Cuban’s CivicaRx, which offers insulin lispro at $35/vial — the most significant insulin affordability initiative in US history.

Humulin / Novolin — Human Insulin (1982 / 1991)

These are recombinant human insulins — chemically identical to the insulin the human pancreas produces, manufactured via bacterial fermentation. Humulin (Lilly, 1982) was the first recombinant human insulin ever approved by the FDA and replaced animal-derived insulins that had been used since the 1920s. Novolin (Novo Nordisk, 1991) followed. They are available over-the-counter at Walmart for $25/vial — the lowest-cost insulin option in the US. The trade-off: human regular insulin has a slower onset (30–60 minutes) and longer duration than analogs, requiring injection 30 minutes before meals — a timing requirement that is behaviorally difficult and metabolically imprecise. NPH (neutral protamine Hagedorn) is the intermediate-acting human insulin — duration 12–18 hours with a peak at 4–12 hours, which causes predictable nocturnal hypoglycemia and has largely been replaced by analogs except in cost-constrained settings.

Insulin Type Quick Reference

When Insulin Becomes Necessary in T2D

Type 2 diabetes is a progressive disease. Beta-cell function — the pancreatic cells that produce insulin — declines by approximately 4–5% per year after diagnosis regardless of what medications are used. Eventually, many T2D patients reach a point where their remaining beta-cell mass simply cannot produce enough insulin to keep up with demand, even with optimal oral or injectable agents. That is when insulin becomes necessary.

The ADA 2023 guidelines recommend considering insulin initiation when: HbA1c remains above target despite optimized multi-drug therapy; HbA1c is extremely elevated at diagnosis (above 10–11%); symptoms of hyperglycemia are severe; or there is concern for Type 1 or LADA (latent autoimmune diabetes in adults) misclassified as Type 2.

Starting with basal insulin alone is appropriate for most T2D patients. Continuing non-insulin agents alongside basal insulin is recommended — metformin and GLP-1s or SGLT2s in particular can be continued with insulin and reduce total insulin dose requirements.

Side Effects

Hypoglycemia — The most important risk. Unlike GLP-1s or SGLT2s, insulin lowers blood glucose regardless of what glucose level you start from. Too much insulin — from an excessive dose, a missed meal, unplanned exercise, or alcohol — causes blood glucose to drop dangerously. Severe hypoglycemia (below 54 mg/dL with symptoms, or any level with unconsciousness) is a medical emergency. Every person on insulin should have glucagon rescue available and should educate household members on its use.

Weight gain — Insulin is anabolic. It promotes fat storage, increases appetite, and causes fluid retention. T2D patients starting insulin typically gain 2–4 kg in the first year. This is the metabolic paradox of insulin therapy: the medication necessary to control glucose also makes weight management harder — and weight is a primary driver of insulin resistance. Combining insulin with a GLP-1 or SGLT2 can substantially offset weight gain.

Lipohypertrophy — Repeated injections at the same site cause fatty tissue to build up under the skin. Lipohypertrophic tissue absorbs insulin erratically — absorption may be delayed, irregular, or variable, causing unpredictable glucose excursions. Rotating injection sites systematically prevents this. If you have been injecting in the same spot for months or years, feel for firm, rubbery patches — that is lipohypertrophy.

Injection site reactions — Redness, itching, and bruising are common, especially early in therapy. True insulin allergy is rare with modern recombinant human insulins.

Dawn phenomenon and Somogyi effect — Two causes of elevated morning glucose. The dawn phenomenon is a natural cortisol and growth hormone surge in the pre-dawn hours that raises glucose. The Somogyi effect (now debated in its frequency) involves rebound hyperglycemia following nocturnal hypoglycemia. CGM data helps distinguish them. Adjusting basal insulin timing or dose addresses both.

The Cost Crisis — And What Changed

Insulin pricing in the United States became a national scandal in the 2010s. List prices for Lantus, Humalog, and Novolog rose by 400–700% between 2001 and 2019 — the result of a rebate system that inflated list prices while PBMs and insurers captured the spread. People were rationing insulin. People were dying from rationing insulin.

The policy response came in stages. The Inflation Reduction Act (2022) capped insulin cost-sharing at $35/month for Medicare beneficiaries. Eli Lilly unilaterally capped out-of-pocket insulin costs at $35/month in 2023 for all patients; Novo Nordisk and Sanofi followed. Walmart partnered with Civica to offer $35/vial private-label insulin. Biosimilar approvals (Basaglar, Semglee, Admelog) created price competition for the first time. The insulin pricing crisis is not fully resolved, but the worst abuses have been partially addressed — at least for the time being.

1. Marso SP, et al. (2017). Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes. NEJM. DEVOTE trial.
2. Riddle MC, et al. (2000). The Treat-to-Target Trial: Randomized Addition of Glargine or Human NPH Insulin to Oral Therapy of Type 2 Diabetic Patients. Diabetes Care. Lantus pivotal trial.
3. American Diabetes Association (2023). Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2023. Diabetes Care.
4. Lipska KJ, et al. (2019). Use of Preventive Drugs Among People with Diabetes at High Risk for Hypoglycemia. JAMA Intern Med.
5. Cefalu WT, et al. (2018). Insulin Access and Affordability Working Group: Conclusions and Recommendations. Diabetes Care.