Insulins differ significantly in their action profiles. Rapid-acting insulins, which are used at mealtimes or for correction, rise quickly in the blood and decline just as fast. In contrast, intermediate-/long-acting (basal) insulins have a completely different profile, sometimes lasting more than 24 hours. It is important to know the action profile of your insulin in order to assess or avoid overlaps. This is an important topic in diabetes education.
Explanations on the Duration of Insulin Action
Insulins are injected subcutaneously (s.c.), that is, into the subcutaneous fat tissue. The duration of action of an insulin depends on its dose: the higher the dose, the longer the duration. A regular insulin, for example, can act much longer than 4 hours at high doses. The same applies to intermediate-/long-acting insulins.
The information found on the internet and in various tables only provides approximate ranges of action; they do not represent exact times. The onset of insulin action, the time to maximum effect, and the duration of action are all dose-dependent. In particular, the duration of insulin action can be greatly prolonged with very high doses.
The information provided by manufacturers in the patient leaflet or product information refers to “normal” insulin dosages. Furthermore, in practice, a number of uncertainties arise that explain differences compared with values determined in pharmacological standard studies. These include, among others, insulin absorption in the subcutaneous tissue, which depends for example on the injection site (abdomen, arm, leg) and skin temperature. A person’s insulin resistance also plays a role: it is lower during or after physical activity, but higher in situations such as illness or colds. Medication use also has an impact. Therefore, pharmacological data on insulin should only be regarded as indicating a range of possible values.
Finally, the insulin levels shown in documents following an injection/infusion only reflect the pharmacokinetics of the preparation. What really matters is the insulin’s effect in the individual’s body. It should also be kept in mind that insulin is only one of many factors influencing blood glucose levels. There are numerous influences—on the website Making Sense of Diabetes by the DiaTribe Foundation, no fewer than 42 such factors are listed (Fig. T1D 1 [1]).
Food:
Carbohydrate quantity, Carbohydrate Type, Fat, Protein, Caffeine, Alcohol, Meal timing, Dehydration, Personal microbiome
Medication:
Medication dose, Medication timing, Medication interactions, Steroid administration, Niacin (Vitamin B3)
Physical activity
Light exercises, High intense and moderate exercises,Level of Fitness, Time of day, social pressure,
Biological
insufficient sleep, stress and illness, recent hypoglycemia, During sleep blood sugar levels, Dawn phenomenon, Infusion set issues, Scar tissue/lipodystrophy, Intramuscular insulin delivery, Allergies, High blood sugar levels, Periods (menstruation), Puberty, Celiac disease, Smoking
Enviromental
expired insulin, inaccurate blood glucose reading, outside temperature, sunburn, altitude
Behavior and decision-making
More frequent blood glucose measurements, Default options and choices, Decision making biases, Family and social pressure.
Which insulins are available for treatment?
The principle of rapid-acting insulin analogs
The principle behind the development of short-acting insulin analogs was primarily the modification of the insulin molecule’s structure:
In solution, insulin molecules cluster together, forming hexamers when six molecules are bound, or dimers when two are bound. These hexamers are stabilized by zinc ions. By substituting certain amino acids in regular insulin, these hexamers can be made to dissociate more quickly in the subcutaneous fat tissue after injection.
Ultra-rapid-acting insulin analogs
An even faster absorption of insulin molecules into the bloodstream can be achieved through additives in the insulin formulation, such as EDTA/citric acid, magnesium, Bio-Chaperone, or niacinamide. The addition of niacinamide (vitamin B3) to insulin aspart leads to faster absorption (faster aspart, Fiasp), an ultra-rapid-acting insulin analog introduced in 2017.
By contrast, Lyumjev (ultra-rapid lispro) is a formulation of insulin lispro containing citrate and treprostinil. Citrate increases local vascular permeability, while treprostinil, a prostacyclin analog, dilates local blood vessels, thereby accelerating absorption of insulin lispro. Lyumjev has been available since 2020 and can be detected in the serum of patients with type 1 diabetes 5–6 minutes earlier, resulting in a 7.2-fold higher insulin exposure during the first 15 minutes. These ultra-rapid-acting insulin analogs provide better control of postprandial blood glucose spikes and have a shorter duration of action.
Thus, while rapid-acting insulin analogs typically have an onset of action at 10–20 minutes, a peak effect at about 1 hour, and a duration of action of 4–5 hours, ultra-rapid-acting analogs have an onset of 5–10 minutes, a peak effect at 45 minutes, and a duration of 3–4 hours. Fig. T1D 2 illustrates these differences in postprandial glucose concentrations following a standard meal and subcutaneous injection of the rapid-acting insulin analogs Humalog and NovoRapid
Fig. T1D 2: Comparison of postprandial glucose concentration after a standard meal and subcutaneous injection of the rapid-acting insulin analogs (Humalog and NovoRapid) and the ultra-rapid-acting insulin analogs Fiasp and Lyumjev [2]
Rapid-acting insulin analogs available in Germany:
Additionally, there are so-called biosimilar insulins, such as:
Ultra-rapid-acting insulin analogs available in Germany:
Most rapid-acting and ultra-rapid-acting insulin analogs are available in a U100 concentration (100 units/milliliter) and come as 10 ml vials, cartridges for insulin pens, and prefilled pens. However, Humalog is also available in a U200 concentration as a prefilled pen, which is particularly useful for patients requiring high insulin doses.
In addition, NovoRapid and Fiasp are also available as PumpCards with a 1.6 ml filling volume for use in insulin pumps.
An overview of currently available insulin analogs can be found on diabetes-news.
Short-acting human insulins available:
Both are available in U100 concentration, in 10 ml vials, cartridges for insulin pens, and prefilled pens.
Another human insulin is the pump insulin:
For short-acting human insulins, onset of action occurs after 20–30 minutes, the peak effect at about 2 hours, and duration of action at 5–6 hours.
For basal insulin therapy, the focus was on extending the duration of action. This was already a goal in the early years of insulin therapy to reduce the number of painful daily injections (due to thick, poorly sharpened needles at the time).
The prolonged action of insulin is achieved by adding zinc and/or neutral protamine Hagedorn (NPH insulin)—through binding insulin to protamine. These insulins are cloudy suspensions, not clear solutions, and must be gently rolled at least 20 times (not shaken) before use to ensure even distribution of insulin molecules. The first NPH insulin became available in 1936. These intermediate-acting insulins played an important role in covering the basal insulin requirement in intensified conventional insulin therapy (ICT) and are still in use today.
Onset of action begins 1.5–2 hours after injection, peak effect occurs at 4–6 hours, and duration of action lasts 8–12 hours.
NPH insulins available in Germany:
Because many patients had to inject NPH insulins twice daily, the focus in recent decades was on developing longer-acting insulin analogs.
By substituting certain amino acids, insulin molecules adhere to each other longer in subcutaneous fat tissue and dissociate more slowly into monomers that enter the bloodstream. The first long-acting insulin analog was insulin glargine, effective for over 24 hours and available since 2000. Onset of action occurs after 1–2 hours. After the patent expired, chemically identical “biosimilars” were introduced by other companies. In addition, attaching a fatty acid chain (as in detemir/degludec) further prolongs the action, since these insulins bind to albumin in the blood and are released slowly.
Long-acting insulin analogs available in Germany:
Additionally:
The goal of further extending insulin action—ideally up to one week—led to the development of ultra-long-acting insulin analogs. By modifying amino acids, degradation is slowed, making the insulin more stable. This allows higher concentrations to be administered and remain in the bloodstream, without forming a depot in the skin. The insulin binds to albumin in the blood and has weaker binding to insulin receptors, extending its duration of action.
After the first injection, high daily levels are achieved without excessive glucose lowering. A steady state is reached after 3–4 weeks. A weekly dose of 70 units produces an effect comparable to a starting dose of glargine.
Available ultra-long-acting insulin in Germany:
Awiqli® (insulin icodec, U700 in prefilled pen; duration approx. 8 days)
| Insulin Type / Analog | Some Brand Names / Notable Products | Europe | USA | India / Indian / local brands & biosimilars |
|---|---|---|---|---|
| NPH insulin (intermediate human insulin) | Humulin N, Novolin N | Available in many European countries under Humulin N / Novolin N | Humulin N, Novolin N | Often available as human NPH insulin under generic or branded versions |
| Insulin glargine (long-acting analog) | Lantus, Basaglar / Abasaglar, Lusduna, Semglee, Rezvoglar, Toujeo (300 U/mL) | Lantus (originator), Abasaglar (biosimilar in EU) (Wikipedia) Also Lusduna, Semglee in EU (Wikipedia) | Lantus, Basaglar (biosimilar) (NCBI) Also Toujeo (concentrated 300 U/mL glargine) (Wikipedia) Semglee and Rezvoglar (biosimilars) (Wikipedia) | In India, manufacturers offer glargine / glargine biosimilars (e.g. “Basalog”) via Indian companies (e.g. Biocon) (Wikipedia) |
| Insulin detemir (long-acting analog) | Levemir | In European markets under the brand Levemir (Novo Nordisk) (NCBI) | Levemir (same) (NCBI) | Available in India under same brand / licensed forms |
| Insulin degludec (ultra-long-acting analog) | Tresiba | Marketed in Europe under Tresiba (Novo Nordisk) (Wikipedia) | Tresiba (U100 / U200) in USA (Wikipedia) | Present in India under same brand or via distribution (some Indian sources list degludec) |
| Glargine 300 U/mL (concentrated glargine) | Toujeo | Available in Europe as a more concentrated form of glargine (300 U/mL) under Toujeo | U.S. uses Toujeo for glargine 300 U/mL (Wikipedia) | Toujeo has been launched in India (as a long-acting basal analog) (Wikipedia) |
| Insulin icodec (once-weekly basal analog) | Awiqli (brand name in EU) | Approved in Europe under brand “Awiqli” for once-weekly basal insulin (icodec) (Reuters) | As of now (2025), not yet fully on the U.S. market / under review (Reuters) | Not widely marketed in India yet (no strong public brand listing found) |
Fig. T1D 3: Action profiles of different basal insulins (NPH insulin vs. insulin analogs) according to pharmacodynamic studies (clamp trials) [3]
As obesity continues to increase, ever-higher insulin doses are needed to normalize blood glucose. This creates a problem with the amount of liquid injected at one site. Until recently, all insulins had a concentration of 100 IU/ml. Normally, no more than 40 units should be injected subcutaneously at one site. If higher doses were needed, the patient had to inject twice. For this reason, insulin manufacturers developed higher-concentration insulins. For example, Humalog is also available in a concentration of 200 IU/ml. In the USA, insulins with 500 IU/ml are even approved. With insulin glargine formulated at 300 IU/ml (Toujeo), the higher concentration also results in an extended duration of action of 32 hours (compared to 24 hours at U100).
NPH insulins and long-acting insulin analogs are used in so-called BOT (basal-supported oral therapy). If the individually targeted HbA1c cannot be achieved with tablets or GLP-1 receptor agonists, basal-supported oral therapy (BOT) is often the next step.
In basal-bolus therapy or intensified conventional therapy (ICT), regular insulin or rapid-acting insulin analogs are administered at mealtimes in addition to a basal insulin.
For selected patients, especially older adults with type 2 diabetes, premixed insulins are available to reduce the number of daily injections and simplify therapy. Premixed insulins are a ready-made combination of a human insulin or a rapid-acting insulin analog with a basal insulin. They are usually injected before breakfast and before dinner. Due to the basal insulin component, they also cover insulin needs around lunchtime, including smaller meals. However, premixed insulins do not achieve physiological insulin levels. Essentially, food intake must be adjusted (“eating against the insulin curve”) at times when insulin levels are excessive. This often results in additional food intake, which must be considered in meal planning. For patients with type 1 diabetes, premixed insulins are obsolete and are reserved for exceptional cases, to be evaluated by the diabetes care team together with the patient.
Premixed insulins available in Germany:
Analog/NPH mixes:
Human insulin/NPH mixes:
Note: The first number indicates the proportion of short-acting insulin; the second number (only in Berlinsulin H 30/70) indicates the proportion of long-acting insulin.
There are also combinations of long- or ultra-long-acting insulin analogs with a GLP-1 receptor agonist:
In addition, the analog insulin mix insulin degludec/insulin aspart (Ryzodeg® 70/30) is available, also only through foreign pharmacies.
Porcine insulins are also available through foreign pharmacies, including:
[1] 42 Factors That Affect Blood Glucose?! A Surprising Update | DiaTribe, last accessed: 26.05.2025
[2] Heise T, Linnebjerg H, Coutant D, et al. Ultra rapid lispro lowers postprandial glucose and more closely matches normal physiological glucose response compared to other rapid insulin analogues: A phase 1 randomized, crossover study. Diabetes Obes Metab. 2020;22(10):1789–1798
[3] Basal insulin in type 2 diabetes – Endocrinology & Diabetology, last accessed: 14.05.2025
.