GLP-1 & Thyroid Cancer: Separating Fact from Fear!

GLP-1 Medications: From Diabetes Management to Weight Loss

While reducing weight has been shown to decrease both the risk of chronic diseases and early death in people with obesity, it can be difficult to achieve and sustain. The intestinal hormone GLP-1 (glucagon-like peptide-1) has become known not only to stimulate insulin release to control blood sugar levels but also acts on the brain to reduce appetite and delay the emptying of the stomach, both of which promote satiety. Medications that mimic the activity of GLP-1 (“agonists”) have shown promising results in both managing diabetic metabolism and facilitating excess weight loss.

The efficacy of GLP-1 medications in promoting excess weight loss in diabetic patients has sparked interest in their potential as dedicated anti-obesity treatments. Clinical trials have demonstrated significant reductions in body weight, far exceeding the effects of lifestyle interventions alone. These findings herald a new frontier in obesity therapy, offering hope for individuals struggling to achieve meaningful weight loss.

Effects of Different GLP-1 Medicines on Obesity

Areesha Moiz, from McGill University in Montreal, and colleagues published a review on the efficacy and safety of GLP-1 RAs and co-agonists for obesity treatment in January 2025. They summarized 26 studies of “placebo-controlled randomized controlled trials (RCTs)” in otherwise healthy adults with overweight or obesity.

What does “placebo-controlled randomized controlled trials (RCTs)” mean? Let us explain such clinical study designs:
Participants of a study are divided into different groups by drawing lots (“randomized”). One group gets an injection containing GLP-1 medicine, the other group gets an injection containing only water (placebo). As the participants often go to the study nurses and doctors and get weight and blood controls, this care alone can have some effect, called “the placebo effect”. The effect of the medicine is therefore measured against the placebo treatment, the placebo group is the “control”. Neither the participants nor the study nurses or treating doctors know whether the injections carry the medicine or not (“double-blind” study design). Only the study manager wo perform the final scientific evaluation know by codes which patient received medication, and which received placebo.

In summary, 15,491 participants and 12 agents (three commercially available and nine premarket), were included in the reviewed studies. The researchers at McGill University Montreal found that

tirzepatide (15 mg once weekly, “Zepound”) resulted in weight loss of up to 17.8% after 72 weeks,
semaglutide (2.4 mg once weekly, “Wegovy”) resulted in weight loss of up to 13.9% after 68 weeks,
liraglutide (3.0 mg once daily, “Saxenda”) resulted in weight loss of up to 5.8% after 26 weeks,
retatrutide (12 mg once weekly, not approved for prescription yet) resulted in weight loss of up to 22.1% after 48 weeks

compared with placebo.

Tirzepatide and Retatrutide are examples of the new class of “dual-action” weight loss injections targeting GLP-1 (like Wegovy) and GIP, another hormone involved in metabolism and appetite regulation. Their weight loss effect is even more pronounced than the classical GPL-1 medicines. However, a healthy weight loss is assumed to be no more than 2 kg per month. If excess weight is reduced too fast, people not only loose fat mass, but – unwanted – also muscle tissue. This should be prevented, and first trials with new medications addresses this aspect. Healthy weight reduction should be regarded as a marathon, not a sprint, and should be accompanied by enhancing physical activity and a healthy diet to have the chance to be sustainable.

Side-Effects of GLP-1 Medicines – The Thyroid Cancer Concern

The most common side effects of GLP-1 medicines include loss of appetite, nausea, vomiting, or diarrhea. These side effects are more likely to happen when starting the medication or taking an increased dose. A severe — but rare — side effect of GLP-1 treatment can be pancreatitis.

Recent findings raised the question, whether GLP-1 medicines might also increase the risk to develop thyroid cancer. It’s critical to properly evaluate scientific findings and draw the right conclusions. For your better comprehension, let’s talk about an article written by Nancy A. Melville and published in Medscape Public Health at the end of January 2025:

Thyroid cancer concerns surrounding GLP-1 RAs stem from experimental studies showing a risk for medullary thyroid cancer in mice and rats, resulting in a warning from the US Food and Drug Administration recommending that those with a family history of the condition should avoid these medicines. More recent studies showing that human papillary thyroid cancer cells have GLP-1 receptors and might be activated by GLP-1 medicines has further raised concerns of a risk beyond medullary thyroid cancer. However, recent studies evaluating the risk have been inconclusive.

The notably increased rate of thyroid cancer detections is limited only to the first year after drug initiation — but not later. And this higher thyroid cancer findings are coupled with an increased rate of thyroid cancer screening during that period.

Rozalina G. McCoy, from the University of Maryland School of Medicine, Baltimore, US, told Medscape Medical News “Our study confirms the increased likelihood of being diagnosed with what appears to be low-risk thyroid cancer after treatment with GLP-1 RAs — but not because patients treated with GLP-1 RAs are more likely to develop thyroid cancer but rather because they are more likely to be diagnosed with it because we, as clinicians, are more likely to look for it.”

The important finding of McCoy and her colleagues was that the risk for thyroid cancer was significantly higher only within the first year after GLP-1 treatment initiation. With the latency period for the development of thyroid cancer from external exposures taking several years (such as radiation, taking approximately 2.5 years), it is implausible for a cancer to develop so soon. Therefore, cancers detected that rapidly after starting a medical treatment are considered to likely have been found due to stepped up screening resulting from an increased concern of thyroid cancer with GLP-1 use. In support of that theory, the study showed that those in the GLP-1 group had a significantly higher rate of receiving thyroid ultrasounds than those in the study groups receiving other control medications. This raises the suggestion that a thyroid cancer concern among the millions of patients taking the immensely popular GLP-1 drugs could exacerbate the already problematic over-detection of incidental thyroid cancers.

Another recent study performed by Bjorn Pasternak, Department of Medicine, Karolinska Institute, Stockholm, Sweden evaluated the risk for thyroid cancer among patients receiving GLP-1s with a longer follow-up of 3.9 years. He and his colleagues reported similar findings — the overall risk for thyroid cancer with GLP-1s was not increased, and the risk beginning 1 year after treatment initiation was even lower. However, only looking at the first year alone the risk in was again higher. “Our analyses indicating a nominally increased risk restricted to the first year after starting treatment might be consistent with an increased detection of thyroid cancer among patients using GLP-1 RAs,” he told Medscape Medical News.

Rise in Incidental Thyroid Cancer Detection, An Ongoing Concern

The advent of more advanced imaging and thyroid cancer testing in recent years has already led to a significant problem of over-detection and sometimes over-treatment of incidental, small thyroid cancers that will likely remain harmless in the majority of patients.

With approximately 64 million prescriptions of GLP-1 RAs dispensed between 2000 and 2015 and the percentage increasing at a rate of about 10%-30% per year, increased thyroid testing among those patients could indeed add to the problem.

Meanwhile, thyroid testing is currently not recommended for patients on GLP-1s who do not have a thyroid cancer risk, and the results from the current and Pasternak’s studies, as well as several other recent studies, appear to support those recommendations.

McCoy underscored that overdiagnosis can have important implications, sharing her own personal experience on the receiving end of a cancer diagnosis. “Overdiagnosis of these low-risk thyroid cancers may ultimately lead to more harm for the patient than not making the diagnosis, since surgery for thyroid cancer carries real risks (including of death) and there are downstream consequences to having your thyroid removed and relying on lifelong hormone replacement. As a cancer survivor myself, though of lymphoma, not thyroid cancer, I also know the profound impact that a cancer diagnosis has on the individual and their loved ones,” McCoy said. “It is not something I would wish for anyone, which is why I always speak to my patients about searching for something we may not want to—or need to—find.”