What’s New in Primary Care: Spring ‘25
Hello everyone!
I hope everyone is enjoying the Spring weather with nature awakening from its
slumber and blooming around us. I’ve decided to devote this entire writing to discuss a class of
medication called GLP-1 agonists. You may have already heard of the brand names Ozempic,
Wegovy (semaglutide), Mounjaro, and Zepbound (tirzepatide).
What is GLP-1 and what does it do?
GLP-1 stands for glucagon like peptide-1. This is a naturally occurring hormone in the
human body, which helps regulate blood sugar, energy intake, and other metabolic processes.
When we eat a meal, GLP-1 is released when our stomachs start to fill. In addition when the
food gets digested and released into the small intestine more GLP-1 gets released into the
bloodstream. The hormone sends signals to other places in our bodies including our brains,
which results in feeling full from the meal as well as lowering our blood sugars.
Because of the blood sugar lowering effect, these drugs were initially developed to treat
diabetes. As time went on, more discoveries were made regarding the beneficial effects of
the medications in multiple other areas of the body- with the most well known and publicized effect of these drugs was the remarkable ability for patients to lose weight even in people without diabetes.
What are some of the other effects of the GLP-1 medications being discovered?
There have been many findings showing improvement/prevention of illnesses in other
areas of the body:
-In the brain there is mounting evidence regarding prevention of dementia, and patients
taking GLP-1s have had fewer strokes. In addition there are ongoing studies regarding
treatment of depression and substance abuse disorders (alcohol and other drugs of abuse)
which look quite promising.
-Heart patients have had fewer heart attacks and less hospitalizations for heart
failure.
-Patients’ liver fat levels have been shown to decrease resulting in less “fatty Liver” which
affects approximately 30 percent of Americans. Fatty liver can lead to liver inflammation and a
life threatening condition called cirrhosis.
-GLP-1’s in the bloodstream have been shown to lower harmful cholesterol molecules known as triglycerides, which may prevent hardening of the arteries, and in the vascular system it has been noted that blood pressure is lower- helping to further prevent strokes and heart attacks as well as hardening of the arteries in the legs.
-Additionally, with regards to the kidneys, it has been found the medications lower the risk of developing worsening chronic kidney disease, and in the joints there have been improvements in arthritis symptoms.
Sleep Apnea is now being treated with tirzepatide (FDA approved).
Weight loss averages 15% or more of body weight in patients who are overweight who
take the drugs for approximately one year with many patients achieving higher weight loss
results.
What are potential side effects and other negative factors in taking GLP-1 therapy?
The main limiting side effects of these drugs are nausea/vomiting, heartburn,
constipation, and diarrhea. In addition there are reports of increased problems with gallstones.
Usually, the side effects can be overcome by starting a low dose first and gradually increasing
the dose over a period of weeks to achieve the desired weight loss effects. A full list of currently studied side effects can be found HERE.
Another hindering factor is cost–these medications are relatively expensive, and many
patients have trouble affording them. Insurance coverage is quite variable as of this writing but
in general they are not well covered by insurers. It is felt coverage will improve with time given
the many beneficial effects summarized.
Finally, the fact that these drugs have to be injected into the body weekly can be a major hurdle for some, as a handful of patients cannot tolerate giving themselves shots. On the horizon are oral forms of these medications, so the shot issue should not be as much of a factor in the future.
The final common pathway–overcoming “insulin resistance”
Insulin resistance simply means it takes more insulin to lower blood sugars in tissues in
our bodies to keep our blood sugars balanced compared to baseline. The more adipose (fat) tissue we carry around- especially in our mid sections- the more insulin resistance we develop. Ultimately, some people will develop Type 2 (adult onset) diabetes. It is becoming more apparent high insulin levels can lead to developing increased insulin resistance and “metabolic syndrome”- an all-encompassing term for insulin-derived health issues.
Insulin is pro-inflammatory and therefore may lead to damaged blood vessels (strokes, heart
attacks, kidney problems) as well as other inflamed tissues (arthritis, liver problems). Because
the GLP-1 agonists lower insulin resistance by several mechanisms, they are being shown to help treat/prevent the detrimental effects of insulin resistance and metabolic syndrome on a person’s health.
In summary: the GLP-1 agonists are a new potentially powerful tool in our armamentarium to
treat as well and prevent multiple detrimental metabolic processes in our bodies that can lead to
multiple diseases. The future looks quite promising for this emerging class of medication.
George Bell, MD