by Jessica Pyhtila, PharmD, BCPS, BCGP
If you have insulin-dependent diabetes, you often will take a long-acting basal insulin such as Lantus (insulin glargine) or Levemir (insulin detemir). This may be in combination with a short-acting insulin like Novolog (insulin aspart).
However, within the past few years, several ultra-long-acting insulins have hit pharmacies. Like long-acting insulins, ultra-long-acting insulins are basal insulins. It can be hard to know the difference between long and ultra-long insulins. This article will explore the differences between long-acting and ultra-long-acting insulins, and how to decide with your doctor about which one is right for you.
What is Basal Insulin?
Insulin is produced by the beta cells in your pancreas. Normally, the pancreas produces a steady amount of insulin during the day, whether you are sleeping or awake. This is called basal insulin. After you eat, your pancreatic beta cells produce a burst of insulin, called bolus insulin.
When you have diabetes, your pancreatic beta cells no longer produce enough basal and/or bolus insulin. For this reason, you need to use long-acting (or ultra-long-acting) insulin to replace the basal insulin, and short-acting mealtime insulin to replace your bolus insulin.
Both long and ultra-long-acting insulins have chemical modifications that allow them to release into your bloodstream at a steady rate to mimic basal insulin. These modifications include changes to amino acids, which are the building blocks of all proteins including insulin.
By having slightly altered amino acid structures, long and ultra-long-acting insulins do not become immediately active in your bloodstream once you inject them. Instead, after the liquid is injected under your skin, the insulins either form microprecipitates (insulin glargine) or depots (insulin degludec, insulin detemir), from which insulin is slowly released into your bloodstream to mimic your natural basal insulin production.
What Are Long-Acting Insulins and How Do They Work?
Long-acting insulins keep a relatively steady amount of basal insulin in your bloodstream. However, even though the amount of insulin released is generally consistent, long-acting insulins do have a peak effect around halfway through their duration of action. They don’t start working immediately, but rather have both a slow onset and wearing-off time. Generally, they start working within 2 to 4 hours after injection. As their name suggests, they work for a long time – up to 24 hours.
|Long-acting Insulin Brand Name||Generic name||Time to onset||Time to peak effect||Duration of effect|
|Levemir||Insulin detemir||~2 hours||8 hours||14-24 hours|
|Lantus, Basaglar||Insulin Glargine U-100 (100 units of insulin per mL)||2-4 hours||8-12 hours||20-24 hours|
What Are Ultra-long-acting Insulins and How Do They Work?
Ultra-long-acting insulins were developed after long-acting insulins, in an attempt to model the body’s natural basal insulin more accurately than long-acting insulins. They are similar to long-acting insulins in that they both start working slowly and wear off slowly. However, ultra-long-acting insulins may take even longer to start working and even longer to wear off.
An important difference between long-acting insulins and ultra-long-acting insulins is that ultra-long-acting insulins do not reach a peak level in your body. Instead, they release a consistent level of insulin in your body over the entire time they are active, with no fluctuations. This is what makes ultra-long-acting insulins better physiological matches to how your pancreas works than long-acting insulins, which have a peak. Having no peak effect also reduces the risk of hypoglycemia, or low blood sugar levels.
On average, ultra-long-acting insulins start working within 6 hours, although the exact amount of time can vary depending on the drug. Generally, they last even longer than long-acting insulins. This can be helpful for people who are not getting a full 24-hour benefit from their long-acting insulin, or for people like shift workers who may need to vary the times at which they inject their insulin.
It is important to remember that there is no standard definition of long vs. ultra-long-acting insulins. For this reason, some people may categorize the same insulins in different ways. Some organizations, for example, consider Tresiba to be a long-acting insulin, while others consider it to be an ultra-long-acting insulin.
|Ultra-Long-Acting Insulin Brand name||Generic name||Time to onset||Time to peak effect||Duration of effect|
|Toujeo||Insulin Glargine U-300 (300 units of insulin per mL)||6 hours||No peak||30 hours|
|Tresiba||Insulin Degludec U-100, U-200 (100 or 200 units of insulin per mL)||~2 hours||No peak||42 hours|
Is Insulin Glargine a Long-Acting or an Ultra-Long-Acting Insulin?
Insulin glargine can either be a long-acting or ultra-long-acting insulin, depending on its formulation. When formulated as Lantus, insulin glargine is considered a long-acting insulin which starts working within 4 hours and lasts up to 24 hours. However, when formulated as Toujeo, the insulin is considered ultra-long-acting as it takes up to 6 hours to kick in and lasts for 24 hours or more.
Is Long-Acting Insulin Safer Than Ultra-Long-Acting Insulin?
Long-acting insulin is not necessarily safer than the ultra-long-acting alternative. Research shows that ultra-long-acting insulin has less hypoglycemic risk than long-acting insulin. This is likely because long-acting insulin eventually reaches a small peak level around halfway through the dosing interval, while ultra-long-acting insulin has no peak level.
This lack of a peak also translates into ultra-long-acting insulin putting a person at lower risk for nighttime (nocturnal) low blood sugar events, which also improves safety.
Does Long-Acting Insulin Work Better Than Ultra-Long-Acting Insulin?
Studies have shown that both long-acting and ultra-long-acting insulin work about equally well at controlling blood sugar.
Am I More Likely To Gain Weight on Long-Acting or Ultra-Long-Acting Insulin?
Unfortunately, all insulins are linked to weight gain. Research suggests no difference between the weight a person gains on long-acting insulin versus ultra-long-acting insulin.
In conclusion, both long-acting and ultra-long-acting insulins are good choices to help you control your blood sugar and help mimic the normal insulin release from your pancreas. Both types of insulin work equally well. However, ultra-long-acting insulins may be safer because they carry less of a risk of low blood sugar because they have no fluctuations or peak effect. By working closely with your doctor to manage your diabetes, you can determine whether long-acting or ultra-long-acting insulin is right for you.
University of Michigan Health. “Types of Insulin.” August 31, 2020. Retrieved from: https://www.uofmhealth.org/health-library/aa122570
Davis, Courtney S.; Fleming, Joshua W.; Malinowski, Scott S.; et al. “Ultra-long-acting insulins: A review of efficacy, safety, and implications for practice.” Journal of the American Association of Nurse Practitioners, July 2018. Retrieved from: https://alliedhealth.ceconnection.com/ovidfiles/01741002-201807000-00005.pdf
Drugs.com. “Basaglar.” September 1, 2021. Retrieved from: https://www.drugs.com/pro/basaglar.html