Can GLP-1s Help People Stop Insulin?

A new study led by Kasia Lipska, MD, MHS, associate professor of medicine (endocrinology and metabolism) at Yale School of Medicine, examined the impact of Glucagon-like Peptide-1 Receptor Agonist (GLP-1) therapy on rates of insulin discontinuation in people with type 2 diabetes compared with other oral medications typically prescribed to help manage blood sugar levels. The findings were published in Annals of Internal Medicine.

While insulin therapy is an effective treatment for many individuals with type 2 diabetes, it can be burdensome to take, requiring daily injections and frequent monitoring, and can result in low blood sugar reactions. Studies have shown that GLP-1s can reduce daily insulin requirements, but researchers have yet to determine whether these newer medications can enable safe discontinuation of insulin in people with type 2 diabetes.

For the study, the researchers used U.S. Department of Veterans Affairs (VA) electronic health records data to match 9,000 sets of people based on similar health traits, which they then analyzed by what type 2 diabetes treatment they received: GLP-1, sodium–glucose cotransporter-2 inhibitor, or dipeptidyl peptidase-4 inhibitor. They then analyzed three years of records to see the rate at which those who started each type of medicine were able to stop using insulin. Insulin discontinuation was measured based on when patients stopped filling their insulin prescriptions at the VA.

GLP-1s performed comparably to the other prescription medicines used to treat diabetes, researchers found. All groups discontinued insulin at a similar rate.

The results came as a surprise, says Lipska. “I was wondering how big the effect of GLP-1s would be, not whether there was any effect at all.”

Lipska has several ideas as to why the study did not show that GLP-1 therapy increases the rates of patients stopping insulin therapy. Because the study was not a randomized clinical trial, the data were gathered from routine interactions with clinicians and patients.

“It's very complex,” says Lipska. “Patients often add or switch medications over time, so it becomes very difficult to disentangle,” she says.

Lipska also noted that patients in the study did not advance to a full dose of GLP-1s and were using a weaker version than those currently on the market, which may have dampened the effect.

This study points to a larger issue in diabetes care: There is no standard protocol for discontinuing insulin, Lipska says.

“Most training for diabetes care is about starting and adjusting dose, not stopping or withdrawing,” says Lipska. She explains that when someone is achieving their target blood sugar numbers and taking incrementally smaller doses, that is usually a cue to stop. Even so, many people with type 2 diabetes remain on insulin, possibly because many clinicians are uncertain about stopping it.

“The lesson may be that prescribing a GLP-1 receptor agonist is only the first step,” Lipska says. “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.”

Other Yale authors of the study include Pradeep Mutalik, MD; Barbara Gulanski, MD, MPH; Mihaela Aslan, PhD; and Lei Yan, PhD.