Life with diabetes usually includes many injections of the blood sugar–controlling hormone insulin. Recent research investigating a once-weekly shot finds it might help lessen the burden a bit for some with the disease.
Two pharmaceutical companies have developed weekly insulin formulations and have tested the drugs in late-stage clinical trials. This September, in the New England Journal of Medicine, researchers reported promising results for efsitora, from Eli Lilly. For adults with type 2 diabetes, the drug worked as well as a once-daily formulation of insulin. But a trial of adults with type 1 diabetes, reported the same month in the Lancet, found there were more episodes of dangerously low blood sugar in the group on efsitora than in the group taking a once-daily insulin shot.
Meanwhile icodec, from Novo Nordisk, has received approval for use in adults with diabetes by the European Union and by Canada and a few other countries. But the U.S. Food and Drug Administration announced in July that it is not ready to approve the company’s application for icodec. In May, an FDA advisory committee had voted against moving the drug forward in part due to safety concerns from the increased risk of hypoglycemia — the clinical term for blood sugar that’s too low — for those with type 1 diabetes.
It will likely take time before things shake out on whether, when and for whom weekly insulin will become available in the United States. For now, the clinical trials provide some insight into the usefulness and limitations of a weekly formulation. Science News talked with two experts about weekly insulin, what’s challenging when trying to mimic the body’s system for regulating blood sugar and what else would be helpful for people managing diabetes.
What is diabetes, and how is it treated?
Diabetes develops when blood levels of glucose become too high, because the body has lost the ability to properly regulate this sugar — the body’s main fuel — with the hormone insulin. Type 1 diabetes is an autoimmune disease that destroys the cells in the pancreas that make insulin. With type 2 diabetes, these cells don’t make enough insulin or the body doesn’t respond to insulin effectively, or both. Over time, high levels of blood sugar can harm the kidneys, heart, eyes and nerves.
An estimated 38 million people have diabetes in the United States, nearly 12 percent of the population, according to the U.S. Centers for Disease Control and Prevention. Close to 2 million of those have type 1.
Managing diabetes means monitoring blood sugar levels throughout the day and, for those with type 1 and some with type 2, figuring out how much insulin to take. If an insulin dose is too high, blood sugar drops too much. The effects can be quickly felt, and can include shakiness, nausea, fatigue, hunger, dizziness and irritability, among other symptoms. If blood sugar levels become severely low, a person can become confused, feel weak, have difficulty walking and even lose consciousness. Severe hypoglycemia is a medical emergency.
With diabetes, there’s “a lot of thinking about food and thinking about numbers,” says Laura Young, an endocrinologist specializing in diabetes care at the University of North Carolina School of Medicine in Chapel Hill. “It doesn’t ever stop.”
People with type 1 and some with type 2 can face multiple daily injections of insulin. Short-acting insulin covers the spike in glucose that comes with meals. Long-acting insulin lasting around 24 hours manages the time between meals and at night. Covering three meals and the rest of the day and night adds up to “at least four shots, and that’s probably the minimum,” Young says.
How does the body usually regulate blood sugar, and why is this hard to copy?
Special cells in the pancreas, called beta cells, make insulin (SN: 12/11/07). The beta cells detect the amount of glucose in the blood and secrete the needed amount of insulin, responding to changes in glucose due to meals, exercise, illness and stress. In the body, there’s “continuous regulation to keep sugar in a good range, even if we don’t eat,” says endocrinologist Giulio Romeo of Harvard Medical School and the Joslin Diabetes Center in Boston. “It’s hard to replicate our body’s ability to fine tune” this process, Romeo says.
Insulin injections can’t mimic the responsiveness of beta cells. How quickly a shot of insulin is absorbed into the blood depends upon where the injection is given. And while researchers have made innovative chemical modifications to insulin formulations, creating versions that last for 24 hours or more, long-acting insulins aren’t able to provide the same steady management of glucose between meals that beta cells can.
Instead, there are small highs and lows as long-acting insulin is released, Romeo says. That means there can be a bit too much or a bit too little insulin available over time. Plus, once a dose is taken, “you can’t change it,” Romeo says. If a long-acting dose turned out to be more than needed for the next 24 hours, a person may end up with low blood glucose levels.
How would once-weekly insulin be used?
Once-weekly insulin is meant to take the place of a once-daily long-acting shot. It could make a difference for people’s quality of life “to have to take one less shot a day,” Young says. But the key thing is going to be “making sure that it’s the right dose,” she says. With a once-daily shot, if the dose is too high, “it’s a lot easier to deal with hypoglycemia for that period of time versus the whole entire week.”
In the clinical trials of the two weekly formulations, there were more episodes of severe hypoglycemia in participants with type 1 diabetes taking once-weekly insulin compared with those taking once-daily. This wasn’t an issue with trials of participants with type 2 diabetes.
People with type 2 diabetes “still make a little bit of their own insulin,” Young says, and “for the most part, have lower variability in their blood sugar” than people with type 1 diabetes. That may reduce the risk of ending up with hypoglycemia. Weekly insulin “is certainly promising” for type 2 diabetes, she says. For type 1, “I think they’re going to have to show some more data and be a little more precise” about which people with type 1 might benefit, she says, in terms of their blood sugar variability and other factors.
It’s harder to make needed adjustments “when you’re committing to a medication that is injected once a week,” Romeo says. “I think people with type 1 need a system level of fine-tuning on a day-to-day basis that makes the weekly insulin possibly not the best option in general.”
What other health care improvement would help people manage diabetes?
“Affordability of continuous glucose monitoring systems is really key,” Romeo says, to help broaden access to these devices. Continuous glucose monitors read blood sugar levels 24 hours a day via a sensor placed under the skin. Without this technology, people test for glucose by pricking the finger for drops of blood multiple times a day. The use of continuous glucose monitors to manage diabetes can reduce hospitalizations and improve the quality of life for those on intensive insulin schedules. But it can be difficult to meet the eligibility requirements insurance companies impose to get coverage for the devices, which could cost several thousand dollars out-of-pocket.
Young wishes more people had access to and took advantage of diabetes education, which includes how to monitor blood sugar, how to inject insulin, understanding the impact of activity and different foods on blood glucose and more. A study published in 2022 found that only half of adults with diabetes reported receiving diabetes education. Those who did were more likely to take steps to manage their diabetes and get clinical care than those who didn’t. Diabetes education “seems a little old-fashioned,” Young says, “but it’s really important.”
