A quarter of patients diagnosed with diabetes take a GLP-1 medication. In recent years, this number has been increasing as patients see the effectiveness of the drugs for both weight loss and controlling their diabetes symptoms.

At the same time, many of these patients are also taking insulin, an essential hormone for regulating blood sugar when damaged beta cells in the pancreas can no longer produce enough. However, insulin can also cause a host of negative side effects including weight gain and hypoglycemia. For these reasons, many patients with diabetes hope that taking GLP-1 medications will help them to reduce or discontinue their need for insulin.

Now, in a new study published in the Annals of Internal Medicine, researchers looked to answer this question by comparing the rates of insulin discontinuation in patients taking a variety of diabetes medications. As part of the study, researchers looked at the electronic health records data of nearly 9000 US Department of Veterans Affairs (VA) patients taking either a GLP-1 agonist, SGLT2 inhibitors, or DPP-4 inhibitors.

SGLT2 inhibitors help the body to remove extra sugar through urination and DPP-4 inhibitors help to control blood sugar levels after meals. For the study, researchers found little difference in GLP-1 medications vs these other diabetes medications. But researchers contend that these results aren’t the whole picture.

“The lesson may be that prescribing a GLP-1 receptor agonist is only the first step,” lead study author Kasia Lipska, MD, MHS, an associate professor of medicine at Yale School of Medicine in New Haven, Connecticut, said in a press release. “If we want to help people safely come off insulin, we also need to know when and how to withdraw it. Right now, clinicians have very little guidance for doing that.”

Previous research has already shown that patients taking mealtime short-acting insulin are often able to discontinue use when they are also taking a GLP-1 medication. One study found that short-acting insulin dose reductions or discontinuations promoted positive patient outcomes including the prevention of hypoglycemia and increased weight loss.

The Annals study looked specifically at basal insulin, the long-acting insulin taken once a day that keeps insulin levels steady between meals and overnight, and whether patients could stop taking it with the help of a GLP-1 medication.

Factors Affecting the Decision 

While this is a good first step in the research, the data have some shortcomings that skew its results, said Carolynn Francavilla, MD, a nationally recognized obesity physician who owns and operates Green Mountain Partners for Health and Colorado Weight Care, both in Denver.

In this study, only around 17% of patients were able to discontinue the use of insulin on either the GLP-1 medication or the SGLT2 and DPP-4 inhibitors. While this is a small percentage, the data come from older patients who have likely been taking insulin longer, which makes it more difficult for them to come off the medication. These were VA patients older than 65 years who had an A1c level greater than 9%, meaning they had uncontrolled diabetes.

In these patients, the pancreas and its insulin-producing beta cells are damaged to the point that they can no longer produce enough insulin to control blood sugar. Diabetes is a progressive disease, and as a result, over time it may be more difficult to get off insulin.

“These results don’t surprise me in this patient population because the longer someone has diabetes and the longer they are on insulin, the harder it is to get them off,” said Francavilla.

The study was also mostly done in primary care clinics with only about 10% of patients being seen by an endocrinologist who specialized in diabetes medicine. This means that some of the steps that could have been taken proactively might not have been. Physicians might also have been more cautious in discontinuing use of insulin.

Not to mention that this study only followed semaglutide and not tirzepatide, which is the more powerful of the GLP-1 medications. There’s a question of whether using just one of the medications might have further skewed the results. When compared in a head-to-head study, researchers found that participants lost an average of 20.2% of their weight on tirzepatide and 13.7% on semaglutide. While it hasn’t been studied, the increased weight loss might also affect the need for insulin.

“We often see patients who have maxed out on the benefits of semaglutide see further benefits from tirzepatide,” said Sumeet Jain, MD, an endocrinologist at Rush University in Chicago.

The Full Picture Still Includes GLP-1s

These medications should be used as an incentive for people to make other lifestyle modifications, including diet and exercise, because when people start to see weight loss and health progress, it’s a motivating factor to continue these positive lifestyle changes, said Jain. He added that one weakness of the study is that we don’t know whether diet and exercise education were provided at the same time to help patients succeed in reducing the need for insulin.

“In my clinic, I’m able to help a fair amount of people taking a GLP-1 agonist to get off of insulin, but I don’t tend to find that just prescribing a GLP-1 medication alone and doing nothing else is enough,” said Jain. “It’s the combination of GLP-1s and lifestyle modifications that result in the discontinuation of insulin.”

Ziyad Al-Aly, MD, a renowned epidemiologist who studies GLP-1 medications, contends that the study population is also too small, and if it were higher, researchers might see that GLP-1 drugs can reduce insulin dependence more than the other medications. Though that’s not something we can know for sure unless researchers study a larger population of diabetes patients.

“The results as they presented them show that there is no significant difference between the use of GLP-1s and SGLT2 or DPP-4 inhibitors, but that might not be the whole story,” said Al-Aly.

Additionally, Al-Aly said that this still shouldn’t take away from the broader picture of what we already know about GLP-1s and their association with a laundry list of benefits including weight loss, reduced insulin resistance, improved insulin sensitivity, and reduced cardiovascular events compared with the benefits of SGLT2 or DPP-4 inhibitors.

“I would still favor the use of a GLP-1 vs the others knowing that the benefits that one gets from a GLP-1 are significant in people with diabetes and those with obesity,” said Al-Aly.

The experts cited in this article had no relevant disclosures.