Thyroid issues with GLP1?

We're always on the look out for negative side effects of GLP1 Receptor Agonists.

It's easy to get caught in the upside, but knowing the negative side effects are just as important (if not more) than knowing the positive side effects.

5 second intro to the Thyroid

Your Thyroid is here:

Don't worry if you don't look exactly like the picture.

The job of your Thyroid is to produce hormones (loosely: chemicals that act as signals in your body), and cause your body to perform specific functions.

Here's a quick (old, but good) video to get you up to speed on the basics:

The case of Atrial Fibrillation & Thyrotoxicosis

Don't worry, the words sound very difficult but they basically mean two things:

• Atrial Fibrillation = Fast & Irregular heart rate
• Thyrotoxicosis = Hyperthyroidism = An overly active thyroid (producing an excessive amount of hormones)

You can read about them both online:

Atrial fibrillation - Wikipedia

Wikimedia Foundation, Inc.Contributors to Wikimedia projects

Hyperthyroidism - Wikipedia

Wikimedia Foundation, Inc.Contributors to Wikimedia projects

The 62 year old patient case study

There was a case study which found a 62 year old man experienced atrial fibrillation (a heart attack):

Tirzepatide-Induced Rapid Weight Loss–Related Thyrotoxicosis

This Teachable Moment describes a 62-year-old man with thyrotoxicosis due to excess levothyroxine exposure during tirzepatide treatment that induced rapid weight loss.

JAMA NetworkFor Authors

The facts of this case study are somewhat specific though:

• The patient was predisposed to hypothyroidism (under-active thyroid)
• The patient was prescribed with Levothyroxine (a synthetic form of thyroid hormone, used to treat deficiencies)
• The patient started taking GLP1 (Tirzepatide – active ingredient in Mounjaro and Zepbound)

This lead to an over production of thyroid hormones – which caused an irregular heart rate.

While of course, the outcome isn't nothing , there's less of outright danger due to GLP1s and more a combination of multiple factors causing an issue.

Association with Thyroid Cancer

The other commonly cited issue with GLP1s and Thyroids has been a possible link to Thyroid Cancer.

Papers like the following were first to start the trend/note the possibility of an issue:

Glucagon-like peptide 1 receptor agonists and thyroid cancer: is it the time to be concerned?

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have changed considerably the management of type 2 diabetes (T2D). However, recently published data from retrospective cohort studies suggest that chronic exposure to GLP-1RAs in T2D may increase the…

PubMed Central (PMC)Giuseppe Lisco

It turns out, GLP1s are not significantly associated with Thyroid cancer.

It took a year to get some research that could stand behind that assertion though –

Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study

Objective To investigate whether use of glucagon-like peptide 1 (GLP1) receptor agonists is associated with increased risk of thyroid cancer. Design Scandinavian cohort study. Setting Denmark, Norway, and Sweden, 2007-21. Participants Patients who started GLP1 receptor agonist treatment were compared with patients who started dipeptidyl peptidase 4 (DPP4) inhibitor treatment, and in an additional analysis, patients who started sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment. Main outcome measures Thyroid cancer identified from nationwide cancer registers. An active-comparator new user study design was used to minimise risks of confounding and time related biases from using real world studies of drug effects. Cox regression was used to estimate hazard ratios, controlling for potential confounders with propensity score weighting. Results The mean follow-up time was 3.9 years (standard deviation 3.5 years) in the GLP1 receptor agonist group and 5.4 years (standard deviation 3.5 years) in the DPP4 inhibitor group. 76 of 145 410 patients (incidence rate 1.33 events per 10 000 person years) treated with GLP1 receptor agonists and 184 of 291 667 patients (incidence rate 1.46 events per 10 000 person years) treated with DPP4 inhibitors developed thyroid cancer. GLP1 receptor agonist use was not associated with increased risk of thyroid cancer (hazard ratio 0.93, 95% confidence interval 0.66 to 1.31; rate difference −0.13, 95% confidence interval −0.61 to 0.36 events per 10 000 person years). The hazard ratio for medullary thyroid cancer was 1.19 (0.37 to 3.86). In the additional analysis comparing the GLP1 receptor agonist group with the SGLT2 inhibitor group, the hazard ratio for thyroid cancer was 1.16 (0.65 to 2.05). Conclusions In this large cohort study using nationwide data from three countries, GLP1 receptor agonist use was not associated with a substantially increased risk of thyroid cancer over a mean follow-up of 3.9 years. In the main analysis comparing GLP1 receptor agonists with DPP4 inhibitors, the upper limit of the confidence interval was consistent with no more than a 31% increase in relative risk. No additional data available. The data analysed in this study were based on Scandinavian nationwide register. Individual level data from the registers can only be accessed through secure servers and only export of aggregated data, as presented in research articles, is allowed. Permission to access data can be made only after fulfilling specific requirements to safeguard the anonymity of the study participants and other data safety issues. For these reasons, data cannot be made generally available.

The BMJView ORCID Profile

The important bits are the result:

Results The mean follow-up time was 3.9 years (standard deviation 3.5 years) in the GLP1 receptor agonist group and 5.4 years (standard deviation 3.5 years) in the DPP4 inhibitor group. 76 of 145 410 patients (incidence rate 1.33 events per 10 000 person years) treated with GLP1 receptor agonists and 184 of 291 667 patients (incidence rate 1.46 events per 10 000 person years) treated with DPP4 inhibitors developed thyroid cancer. GLP1 receptor agonist use was not associated with increased risk of thyroid cancer (hazard ratio 0.93, 95% confidence interval 0.66 to 1.31; rate difference −0.13, 95% confidence interval −0.61 to 0.36 events per 10 000 person years). The hazard ratio for medullary thyroid cancer was 1.19 (0.37 to 3.86). In the additional analysis comparing the GLP1 receptor agonist group with the SGLT2 inhibitor group, the hazard ratio for thyroid cancer was 1.16 (0.65 to 2.05).

Given a study of over 145,000 patients, it seems that the risk of GLP1s being explicitly linked to Thyroid cancer has been somewhat put to rest.

We're always on the look out for more information on negative side effects associated with GLP1 Receptor Agonists, but for now, it seems like GLP1s aren't unduly negatively affecting thyroids.