Show 1453: From Lizard Spit to Ozempic: Rethinking How We Treat Diabetes

Diabetes is a serious metabolic disorder that affects close to 40 million Americans. Most of them have type 2 diabetes, which means their bodies produce insulin, but their cells are not very responsive to it. As a result, blood sugar builds up and people run the risk of cardiovascular complications like heart attacks or strokes, along with kidney disease or vision problems. Nerve damage and even dementia appear to be more common among people with diabetes. Should we be rethinking the way we treat diabetes?

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Rethinking How We Treat Diabetes:

Our guest, Dr. John Buse, is known for his decades of diabetes research. We began our conversation by asking about his most recent study, called CATALYST. It considered the effects of a medicine that is not usually thought of as a method to treat diabetes: mifepristone. This research highlighted the impact of high cortisol levels (Diabetes Care, Dec. 1, 2025). This placebo-controlled trial compared the effects of mifepristone, which moderates the effects of this stress hormone, to those of placebo.

Although many people found that mifepristone (Korlym) was difficult to take because of side effects, those who stuck with it lowered their HbA1c significantly. That is a measure of blood glucose over weeks rather than an instantaneous read-out. They also lost weight and waist circumference, on average about two belt notches. That made it a bit easier for their bodies to control their blood sugar. Consequently, some needed lower doses or fewer diabetes medicines.

One advantage of this study is that it may help explain why some people have hard-to-control diabetes. Until now, neither patients nor doctors knew why, even though they were trying hard, some patients couldn’t make any progress. Dr. Buse admits that physicians used to blame patients, assuming they were not following their diet or taking their medicines. Now, seeing the dramatic effects of mitigating cortisol, they are starting to re-evaluate those assumptions. This could change how we treat diabetes.

What Are the Side Effects of Mifepristone?

Despite the benefits, nearly half of the study participants assigned to mifepristone missed out on them. They found the fatigue, nausea, vomiting, headaches joint pain and swelling intolerable. These are the consequences of interfering with cortisol. Some people experience dizziness or increased blood pressure. One particularly dangerous side effect is a drop in potassium, which could affect heart rhythm. People who are having trouble controlling their blood sugar despite their best efforts might ask their physician to check their cortisol levels.

Where Does Lizard Spit Come In?

Several years ago, Dr. Buse talked about lizard spit in one of our interviews. Why in the world would he mention lizard spit? It turns out that one of the components in the saliva of the Gila monster led to the first GLP-1 agonist. Rather than a monster, this is actually a very large venomous lizard native to the Sonora desert. It is illegal to capture or kill a Gila monster in Arizona.

Researchers investigating the chemistry of its saliva developed the drug exenatide (Byetta). Subsequently, drug company researchers came up with a wide range of medications that work through GLP-1. You have probably heard of the best-known, which are semaglutide (Ozempic, Rybelsus, Wegovy) and tirzepatide (Mounjaro, Zepbound). These drugs are already changing the way we treat diabetes.

Can You Reverse Prediabetes?

The lifetime risk for prediabetes is one in three worldwide. But if we could identify and intervene before people actually develop diabetes, we might be able to prevent it. Doctors have been testing lifestyle changes and medications that might be able to keep people with prediabetes from progressing any further down that path. Physical activity can make a big difference, as it changes how the muscles utilize glucose. Changes in diet are also promising, although certainly far from easy for most of us. Doctors can also prescribe drugs like metformin as an early intervention. It is almost as effective as exercise.

Other drugs that are changing the way we treat diabetes include the glitazones (pioglitazone and rosiglitazone). Another category of diabetes drug, those similar to empagliflozin (Jardiance), is already making a difference. Of course, like all medicines, these also can cause adverse effects as well as benefits. One exciting treatment for the future will be gene-modifying technology to treat diabetes. Proof of concept studies have already been conducted.

This Week's Guest:

John Buse, MD, PhD, is the Verne S. Caviness Distinguished Professor of Medicine at the University of North Carolina at Chapel Hill, School of Medicine. He has received international recognition for innovative clinical care and efforts at prevention of type 1 diabetes, type 2 diabetes and their complications.

[caption id="attachment_137693" align="alignnone" width="768"] Dr. John Buse, UNC School of Medicine, Chapel Hill, NC[/caption]