These days you can hardly go anywhere without encountering conversation about GLP-1 medications. Whether it’s the doctor’s office, coworkers at work, commercials on TV, or social media, these medications seem to be ubiquitous. And yet, for all the talk about them, they seem to be raising a lot of questions for people, so our goal is to address some of the most common questions we hear people asking.
First, what exactly are these medications?
The medications we here about most commonly these days fall into one of two categories: GLP-1 (glucagon-like peptide-1) receptor agonists and GIP (gastric inhibitory polypeptide) agonist. This class of medications was originally developed to help control blood sugar levels in type 2 diabetes. Examples of GLP-1 agonists include Ozempic (semaglutide), Saxenda (liraglutide), and Trulicity (dulaglutide). Mounjaro (tirzepatide) is a similar medication, but it targets both GLP-1 and GIP receptors.
So, how do these medications work?
First, a bit of background. GLP-1 and GIP are hormones produced by the body that activate the release of insulin after eating carbohydrates. Insulin is the hormone that allows glucose (the end product of carbohydrate digestion) to be moved from the bloodstream into the cells to be used for fuel. In type 2 diabetes, the insulin response is impaired, so the body doesn’t produce enough as is needed to regulate blood sugar levels after eating. One of the primary ways these medications work is by stimulating increased insulin secretion in response to glucose levels, thereby improving blood glucose control.
In addition to helping control blood sugar levels, these medications also slow the movement of food through the digestive system, which means slower breakdown of food and therefore slower glucose release into the bloodstream. Sometimes this slowed digestion leads to side effects, more on that below. They also block the pancreas from producing glucagon (the hormone that stimulates release of glucose into the blood) if blood sugar levels are high. The slowed movement of food through the digestive system and the inhibition of glucagon also lead to decreased hunger levels. Yet another way they help in type 2 diabetes is to cause an increase in beta cell production (the cells that produce insulin) by the pancreas, and a decrease in beta cell death.
When it comes to type 2 diabetes, these medications are typically considered a second-line treatment after Metformin. Patients who are considered good candidates for GLP-1s include:
Those who do have not reached their target Hemoglobin A1c (a number reflecting average blood glucose levels over three months) after three to six months on other medication
Those who have co-occurring cardiovascular disease, particularly atherosclerosis
Those with heart failure or chronic kidney disease (typically as a third-line treatment alongside a sodium-glucose co-transporter-2 inhibitor [SGLT2i])
GLP-1s for Weight Loss?
Weight loss is a common side effect of this class of medications, so in recent years the FDA has approved formulations of semaglutide (Wegovy) and liraglutide (Zepbound) to be used at higher doses for weight loss in the absence of diabetes. This has many touting these as miracle pills, but there are also concerns that have risen connected to use of these medications, whether for diabetes management or weight loss. Here are a few things to consider:
GI Side Effects
One of the most common side effects of this class of medications is gastrointestinal distress, including nausea, vomiting, diarrhea, and stomach pain. For people with a history of GI issues, especially gastroparesis or inflammatory bowel disease, these medications are contraindicated, and even for those without GI problems, this can overshadow the benefits.
Mental Health Concerns
There has also been speculation that these medications contribute to increased depression and/or suicidal ideation. The labels for Wegovy and Saxenda warn of this possibility, as does the latest approved label for Zepbound. Anecdotally, social media accounts warn of worsening anxiety and panic attacks. However, a meta-analysis published in the American Journal of Geriatric Psychiatry earlier this year stated that these medications contribute to a decrease in depression. More research is required in this area, but it is certainly something to be aware of if you or a family member is taking one of these medications.
Thyroid Cancer
Similarly, there have been some concerns raised about increased risk of thyroid cancer when taking these medications. The journal Diabetes Care published an analysis in 2023 that examined thyroid cancer cases in a cohort of French subjects with type 2 diabetes who have taken GLP-1 receptor agonists. The researchers did find increased risk in people who had used GLP-1 medications for a period of one to three years. Data from retrospective cohort studies looking at long-term exposure to these medications also found a “potential association” with thyroid cancer. However, a study published earlier this year found no increased risk of thyroid cancer. Clearly there is more research to be done in this area.
Long-term Use
Another factor to consider is the fact that these medications are not short-term solutions. Whether being used for blood sugar control in diabetes or weight loss, patients will need to continue taking them to experience the benefits they get while on them. Add to that these medications are still relatively new and are being used in higher doses than previously prescribed, so we don’t have data about the impact of long-term use on overall health
The decision of whether or not to begin taking a GLP-1 agonist is not always straightforward. If you’re wondering whether you should be taking one of these medications, or if you’re already taking one, consider seeking the support of a dietitian. If you haven’t started taking the medication, an RD can assist you in processing through the decision and navigating the maze of information, and if you’re already taking one of these medications, an RD can provide support in making sure you’re getting adequate nutrition while taking the medication and navigating any GI distress you may be experiencing. Whether or not you’re taking medication, an RD can also be a resource for helping you improve your relationship with food and/or your body. You don’t have to figure this out on your own!
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Sources
Bezin, Julien, et al. “GLP-1 Receptor Agonists and the Risk of Thyroid Cancer.” Diabetes Care 46, no. 2 (2023): 384-90. doi: https://doi.org/10.2337/dc22-1148
Chen, Xinda, et al. “The Antidepressant Effects of GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis.” The American Journal of Geriatric Psychiatry 32, no. 1 (2023): P117-P127. doi: https://doi.org/10.1016/j.jagp.2023.08.010
Collins, L., and R. A. Costello. “Glucagon-Like Peptide 1 Receptor Agonists.” In StatPearls. (Treasure Island, FL: StatPearls Publishing, 2024). Available online at www.ncbi.nlm.nih.gov/books/NBK551568.
Gallwitz, Baptist, and Francesco Giorgino. “Clinical Perspectives on the Use of Subcutaneous Formulations of Semaglutide.” Frontiers in Endocrinology 12 (2021). doi: https://doi.org/10.3389/fendo.2021.645507
Garber, Alan J. “Long-Acting Glucagon-Like Peptide 1 Receptor Agonists: A Review of Their Efficacy and Tolerability.” Diabetes Care 34, Supp. 2 (2011): S279-S284. doi: https://doi.org/10.2337/dc11-s231
Hook, Monique, and Lozano, Raechel. “The Psychological Impact of GLP-1 Receptor Agonists: An Ongoing Investigation.” Pharmacy Practice in Focus: Health Systems 13, no. 2 (2024).
Lisco, Guiseppe, et al. “Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: Is It the Time to Be Concerned?” Endocrine Connections 12, no. 11 (2023). doi: https://doi.org/10.1530/EC-23-0257
Pasternak, B., et al. “Glucagon-Like Peptide-1 Receptor Agonist Use and Risk of Thyroid Cancer: Scandinavian Cohort Study.” BMJ (2024): 385:e078225. doi: https://doi.org/10.1136/bmj-2023-078225
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