Once-Weekly Basal Insulins: Better Blood Sugars with Fewer Injections

Updated 7/15/24

If it weren’t for all the data supporting the benefits of once-weekly basal insulin, we might think a once-a-week injection of basal was too good to be true. But clinical trials have shown weekly basal injections to be as beneficial (if not more so) than their daily counterparts in reducing A1c in people with type 2 diabetes. With 52 injections per year as opposed to 365, weekly basal insulin could mean a significantly reduced diabetes management burden for millions of people. Novo Nordisk’s once-weekly basal insulin is under FDA review and may be receiving a decision this month. Lilly’s weekly basal isn’t too far behind, so U.S. approval of this ground-breaking therapy may be closer than we think. European regulatory authorities have already recommended Novo Nordisk’s weekly basal for approval, and final marketing authorization from the European Commission is expected in about two months.

What is Basal Insulin?

Basal insulin is defined as long-acting insulin that is meant to keep glucose levels steady throughout the day and night. It is typically injected once or twice per day depending on the type of insulin (some examples are Lantus, Toujeo, and Tresiba) and individual need. Basal insulin is designed to have no peak or a mild peak, unlike short-acting mealtime insulin. Everyone with type 1 diabetes must take basal insulin, and many people with type 2 diabetes take basal insulin if other medications are not able to get their A1c level to goal.

What Is the Difference between Basal and Bolus Insulin?

Basal insulin provides a steady amount of insulin to control blood sugar between meals and during sleep. In contrast, bolus insulin is short-acting and taken before meal times to prevent blood sugar spikes. It is also taken at other times to correct for unexpected elevated blood sugars.

Types of Basal Insulin

Basal insulin comes in several forms, each designed to meet diverse patient needs and lifestyles. Understanding the types of basal insulin is crucial for choosing the most appropriate therapy. Here’s a breakdown:

Traditional Long-Acting Insulin

These include well-known older options like Lantus and Levemir, which are generally administered once or twice a day. The newer ones, Toujeo and Tresiba, are known for their reliable, steady control over glucose levels throughout the day and night. And no one should be using NPH (a very old intermediate-acting insulin) as their basal in 2024.

Innovative Extended Long-Acting Insulin

Recent advancements have led to the development of extended long-acting insulins like insulin icodec and efsitora alfa, which are designed for less frequent dosing. Administered once weekly, these insulins maintain consistent blood glucose levels with a minimal risk of hypoglycemia, reflecting a major evolution in basal insulin dosing strategies.

How Once-Weekly Basal Insulin Works

Currently, two once-weekly basal insulins are leading the pack in development and clinical trials. As mentioned above, one is from Novo Nordisk and is called insulin icodec. The other is from Lilly and is called efsitora alfa (also sometimes called basal insulin Fc or BIF). Both insulins will get a marketing name once they are approved by the FDA. The effect that allows for weekly insulin administration is a longer half-life of the medication, which means it stays in the body longer than daily insulin. A typical half-life for the daily basal insulin is around 12 hours, versus these new weekly insulins that have a half-life ranging from 8-17 days.

Because the half-life is longer than daily insulins, the weekly insulins also exhibit a more consistent release of insulin and avoid large variability in activity like the peaks and valleys sometimes seen in daily insulin injections. In addition, the weekly insulins will be more concentrated, so giving a week’s worth of insulin won’t actually require a large volume.

Many studies have been ongoing to evaluate the safety and efficacy of weekly insulin, and the results have been positive so far. Icodec was found to be superior in increasing time in range (time in range is the percentage of time that you are between the target blood glucose range of 70 and 180 mg/dL) and lowering A1c when compared to daily insulin. Trials for efsitora alfa have shown that once-weekly dosing was as good as daily dosing with the current basal insulins without any increased risk for hypoglycemia. Many studies have been centered on people with type 2 diabetes specifically. These studies have found that once-weekly insulins show equal blood glucose lowering and no increased risk of hypoglycemia in the type 2 population.

The Benefits of Once-Weekly Basal Insulin

A weekly insulin dosing option could be life-changing for many people because it could help simplify day-to-day diabetes management and cut down on the number of insulin injections. As mentioned above, this has the potential to greatly reduce treatment burden. Weekly basal insulin could also make the process of starting insulin easier for people with type 2 diabetes who would benefit from the therapy but are hesitant to start. It’s been shown to have good tolerability and could also be beneficial for people who live in a medical facility where insulin is administered by a healthcare team.

The Downsides of Once-Weekly Basal Insulin

You may be wondering…what’s the catch? Well, if something were to change dramatically with a person’s health (e.g. they’re suddenly hospitalized and unable to eat), it would be more difficult to change course in managing glucose levels. Keenly aware of this, the developers of these new insulins underwent specific studies to test this by intentionally giving the wrong dose and monitoring closely. They concluded that the risk of hypoglycemia in accidentally doubling or tripling the dose was equivalent to the risk from doubling and tripling the dose of a daily injection, which would be remedied by taking glucose as needed and monitoring blood sugars closely.

There will also be some differences in dosing strategies. Transitioning from a daily basal insulin to a weekly basal insulin will involve a higher loading dose for the first week (giving more of it at first), followed by a maintenance dose. These doses will be in higher unit quantities than a daily basal insulin which may cause confusion, but the doses are not comparable to the daily insulins.

When Will Once-Weekly Basal Insulin Be Available?

As of now, weekly insulins are undergoing evaluation for FDA approval for people with type 2 diabetes. Insulin icodec may be approved as early as this month. Once-weekly insulin is undergoing further studies to evaluate its safety in those with type 1 diabetes.

Could Once-Weekly Insulin Be Right For You?

Once-weekly insulin will ultimately be available for anyone with type 1 or type 2 diabetes, but it will first be commercially available for those with type 2. There are challenges to be aware of and addressed, but it will be a good option for people who simply want fewer injections and a reduced burden of self-management. It will also be beneficial for people who live in a medical facility where insulin is administered by a healthcare team. When approved, weekly basal insulin will have the potential to offer improved adherence, reduced treatment burden, and improved long-term outcomes for many of the millions of people living with diabetes around the world.

Additional Resources:

Overbasalization in Type 1 and Type 2 Diabetes: You Can Have Too Much of a Good Thing!

Higher Dose Basal Insulin in Type 2 Diabetes: Challenges and Solutions

Editor’s Note:

In May 2024, an FDA advisory panel expressed concerns about the potential for insulin icodec to have a higher risk of hypoglycemia in people with type 1 diabetes. 

In July 2024, the FDA rejected Novo Nordisk’s application for insulin icodec, siting manufacturing and other concerns. Novo Nordisk said it is committed to bringing icodec to the U.S. market and will work closely with the FDA to fulfill its requests, though it isn’t likely to happen in 2024. Novo Nordisk has already won approval in the European Union, Canada, Australia, Japan, and Switzerland to sell insulin icodec under the brand name Awiqli for both type 1 and type 2 diabetes. The medicine is also approved in China for type 2 diabetes.