Diabetic and weight loss medications Saxenda®, Ozempic® and Wegovy® are increasingly prescribed for weight loss but are not without risks. And we've already had a patient likely at risk of thyroid cancer whose prescriber put her on it anyway!
Celebrity use and very encouraging statistics like administration of semaglutide, the generic name for the active ingredient in both Wegovy and Ozempic, being able to reduce the risk of serious heart problems such as heart attack, stroke or death in certain patients by 20%, (1) have led to a surge in popularity of these medications. Primary care doctors in particular, who typically have little training in obesity, have found themselves as gatekeepers for these injection drugs that are increasingly being sought by people who don't fit the parameters of study participants and about who it is not clear they should be taking them.
What's All the Hype?
With more than 2 in 5 adults (42.4%) having obesity(2) and the documented cardiovascular benefit of such cardioprotective glucose-lowering drugs among patients with a history of ischemic heart disease (IHD), heart failure (HF), and chronic kidney disease (CKD) as well as secondary prevention of atherosclerotic cardiovascular disease (ASCVD), (3) it is hard to not consider these medications.
Though both Ozempic® and Wegovy® are forms of semaglutide, they differ in dosages and approved uses. Ozempic® was approved in 2017 and marketed for medical use in the treatment of Type 2 diabetes "with weight loss as a secondary effect of the drug’s effects and mechanism of action." It is a lower dose than its counterpart, Wegovy®. If you’ve been prescribed Ozempic® and don’t have diabetes, this is considered off-label use. Ozempic® isn’t approved for use in people under 18 years old. Wegovy® is a higher dose and approved for weight loss but intended for people with a body-mass index (BMI) of 30 or greater. It may also be prescribed for people with a BMI as low as 27 if they have at least one other weight-related concern. Wegovy® is also approved for use among adolescents.
Victoza® and Saxenda® are prescription drugs that use a different generic, liraglutide, but shares the same mechanism of action and risk factors as those above. It is no comfort that the list of adverse side effects for liraglutide has over seventy symptoms and conditions, (4) though some are documented as "rare". Other medications that work the same way include Dulaglutide (Trulicity®)
Exenatide (Byetta®), Exenatide extended-release (Bydureon®) and Lixisenatide (Adlyxin®).
Yet another generic drug in this space is tirzepatide, which is sold under the brand name Mounjaro®, has been approved for use with diabetics but also gets frequent off-label use for weight loss. This is different from the above in that it is also imitates a second hormone, called 'glucose-dependent insulinotropic polypeptide' (GIP), which, along with reducing appetite, may also improve how the body breaks down sugar. And just five days ago it was announced that the Federal Drug Administration (FDA) approved Zepbound®, another form of tirzepatide, for chronic weight management in adults who are obese or overweight and have at least one weight-related health condition such as high blood pressure, high cholesterol, or type 2 diabetes.
How Do They Work?
All of the medications described in this article are classified as 'Glucagon-like peptide-1 agonists' (GLP-1s). They attain blood sugar control by stimulating insulin secretion and inhibiting glucagon secretion without the onset of hypoglycemia, or low blood sugar. "Although their weight loss effects are well known, the mechanism underlying these effects is still debatable. The most notable known mechanisms are linked with the central and peripheral nervous systems through direct activation of the hypothalamus and hindbrain or indirect activation via the vagus nerve, resulting in reduced appetite and food intake".(5) So they increase satiety. And these effects on the vagus nerve are likely how they slow stomach emptying.
And the Health Risks of Using Them Are Still Being Determined?
Just this month was published the first large, population-level study to examine adverse gastrointestinal events in non-diabetic patients using the drugs specifically for weight loss; it found use of the GLP-1s was associated with an increased risk of serious medical conditions including stomach paralysis, pancreatitis and bowel obstruction.(6) More specifically, the risks were determined as:
3.67 times higher risk of stomach paralysis (gastroparesis), which limits the passage of food from the stomach to the small intestine and results in symptoms like vomiting, nausea and abdominal pain.
9.09 times higher risk of pancreatitis, which can cause severe abdominal pain and, in some cases, require hospitalization and surgery and may even result in death.
4.22 times higher risk of bowel obstruction, whereby food is prevented from passing through the small or large intestine, resulting in symptoms like cramping, bloating, nausea and vomiting. Depending on the severity, surgery may be required.
As if that wasn't enough, these medications carry with them, according to a study published in February of this year, "... increased risk of all thyroid cancer and medullary thyroid cancer with use of GLP-1 RA, in particular after 1-3 years of treatment".(7)
My interest on this topic was particularly sparked after a patient, who is already being annually monitored for any of her over a dozen thyroid nodules progressing to a tumor, informed me she was on Saxenda®. I informed her that about the increased risks of thyroid complications and suggested she discontinue the medication immediately, as well as contact the prescribing physician about the matter.
It may not be enough that certain drugs are popular and trending, or even if your doctor prescribed something for you! That does not mean it is safe or the best option for your specific concerns. I often tell my patients that they have to be their own advocates in healthcare. And trendy prescriptions often being sold for off-label use are no exception.
References:
National Institute of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Diabetes Statistics. "Overweight and Obesity Statistics." https://www.niddk.nih.gov/health-information/health-statistics/overweight-obesity Accessed 11-19-2023,
Mahtta, Dhruv et al. “Utilization Rates of SGLT2 Inhibitors and GLP-1 Receptor Agonists and Their Facility-Level Variation Among Patients With Atherosclerotic Cardiovascular Disease and Type 2 Diabetes: Insights From the Department of Veterans Affairs.” Diabetes care vol. 45,2 (2022): 372-380. doi:10.2337/dc21-1815.
The content and any recommendations in this article are for informational purposes only. They are not intended to replace the advice of the reader's own licensed healthcare professional or physician and are not intended to be taken as direct diagnostic or treatment directives. Any treatments described in this article may have known and unknown side effects and/or health hazards. Each reader is solely responsible for his or her own healthcare choices and decisions. The author advises the reader to discuss these ideas with a licensed naturopathic physician.