The relationship between weight-loss drugs like Ozempic and thyroid health has become a topic of increasing interest and concern. While these medications have shown effectiveness in weight management and addressing health issues often linked to obesity, questions have arisen about their potential impact on the thyroid gland, particularly for individuals with pre-existing conditions like hypothyroidism. This article aims to provide a comprehensive overview of the current understanding of the interplay between Ozempic and hypothyroidism, drawing upon available research and expert opinions.
The Rise of Semaglutide for Weight Loss and Diabetes Management
In the past, appetite suppressants containing amphetamines, diuretics, laxatives, and thyroid hormones were marketed for weight loss. Today, drugs like Ozempic, Rybelsus, and Wegovy have emerged as potentially safer options for weight management. These medications fall under the generic identity of semaglutide and are glucagon-like peptide-1 (GLP-1) agonists.
Originally approved by the Food and Drug Administration (FDA) for treating Type 2 diabetes, Ozempic's longer-term studies revealed a significant side effect: weight loss. This discovery spurred interest in using it primarily as a weight-loss drug. Rybelsus is a daily pill, while Ozempic and Wegovy are weekly injections. Wegovy is specifically FDA-approved for weight loss.
How Semaglutide Works
Semaglutide, the active ingredient in these drugs, works by mimicking the effects of the GLP-1 hormone. This leads to increased insulin secretion and decreased glucagon production, which helps regulate blood sugar levels. Additionally, semaglutide slows down gastric emptying, increasing the time it takes for food to pass from the stomach to the intestines. This results in a feeling of fullness, leading to decreased appetite and subsequent weight loss.
FDA Warning and Potential Risks
Despite the benefits, the FDA issued a boxed warning for Ozempic and Wegovy, citing a potential risk of thyroid tumors and cancer. The warning specifically advises individuals with a personal or family history of medullary thyroid cancer (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2) to avoid these medications.
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Dr. McSpadden explains that earlier laboratory studies showed an increased incidence of medullary thyroid cancer, a rare form of thyroid cancer originating from parafollicular C cells. While research hasn't confirmed semaglutide directly causing thyroid cancer in humans, the initial correlation was strong enough for the FDA to issue the warning.
It's important to note that the FDA boxed warning applies to Rybelsus as well. Other potential side effects of semaglutide include pancreatitis, hypoglycemia, gallbladder issues, vision changes, increased heart rate, and depression or suicidal thoughts. The FDA has also issued warnings about overdosing and the potential for developing ileus, a blockage in the colon.
Considerations for Those on Thyroid Medications
Dr. McSpadden advises that semaglutide can affect medication levels, especially for those taking thyroid medications like Synthroid. The delayed gastric emptying caused by semaglutide can increase the absorption of thyroid medications, potentially requiring dosage adjustments.
Balancing Risks and Benefits
For individuals managing Type 2 diabetes and struggling with weight loss, the benefits of Ozempic, Rybelsus, and Wegovy may outweigh the potential risks. Better blood glucose control can positively impact various areas of the body, including the kidneys and cardiovascular system. Weight loss can also improve blood pressure and decrease sleep apnea.
However, individuals already on thyroid medications may need more frequent monitoring and adjustments due to absorption changes and weight loss. Routine thyroid checks are generally recommended, including physical examinations and thyroid function labs.
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Ozempic and Common Thyroid Conditions: Hypothyroidism and Hyperthyroidism
For most individuals with common thyroid conditions like hypothyroidism or hyperthyroidism, Ozempic is generally considered safe. Dr. Zaid Fadul, CEO of Bespoke Concierge MD, suggests that it may even be beneficial for those with hypothyroidism by aiding weight loss, which can potentially improve thyroid levels.
It's crucial to remember that individuals with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2) should not use Ozempic.
The Impact of Weight Loss on Hypothyroidism
Weight loss associated with GLP-1s like Ozempic can be beneficial for individuals with hypothyroidism. Hypothyroidism occurs when the thyroid gland doesn't produce enough thyroid hormone, leading to symptoms like weight gain, fatigue, dry skin, and brain fog.
Elizabeth Van Dril, Pharm.D., a clinical pharmacist, notes that weight loss on Ozempic can lead to reductions in thyroid-stimulating hormone (TSH) levels, suggesting a potential improvement in thyroid function and a need for lower doses of thyroid replacement therapy.
Ozempic and Hyperthyroidism
Ozempic is also considered safe for individuals with hyperthyroidism. Dr. Cunningham states that there is no interaction between Ozempic and common hyperthyroidism medications like Tapazole (methimazole) and propylthiouracil. Additionally, there is no evidence that hyperthyroidism reduces the effectiveness of semaglutide.
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Ozempic and Thyroid Cancer: Emerging Research
While concerns exist regarding medullary thyroid cancer, some initial research suggests that Ozempic may be helpful in suppressing papillary thyroid carcinoma (PTC) growth and reducing tumor size. However, these findings are preliminary and require confirmation through clinical studies.
It's important to remember that Ozempic doesn't directly regulate thyroid levels like it regulates blood sugar levels. However, it may indirectly affect thyroid levels, especially for individuals with hypothyroidism. Dr. Fadul recommends follow-up thyroid testing every three to six months during the first year of Ozempic use and being prepared for potential dose adjustments of thyroid replacement medication.
Weight Loss with Hypothyroidism: A Complex Challenge
Losing weight can be particularly challenging for individuals with hypothyroidism. Even slight changes in thyroid hormone levels can lead to weight gain or difficulty losing weight. Hypothyroidism affects the regulation of growth and development, metabolism, breakdown of fat, sugar, and protein, and muscle control.
When the thyroid is underactive, it can't produce enough thyroid hormone, leading to a slowed metabolism, fatigue, changes in fat and blood sugar metabolism, and water retention, all contributing to weight gain. While thyroid replacement medication can lead to weight loss, studies suggest that this is primarily due to water excretion and that thyroid hormones can increase appetite and caloric intake.
Semaglutide (Wegovy) as a Weight Management Tool
Semaglutide (Wegovy) is an FDA-approved medication for chronic weight management. It belongs to the GLP-1 receptor agonist class, regulating appetite and calorie intake, leading to weight loss and a lower body mass index. Studies have shown that GLP-1 agonists can help reduce body weight in obese patients, regardless of diabetes status.
Semaglutide is administered as a weekly subcutaneous injection, with a gradual dose increase to minimize side effects. While Ozempic and Rybelsus are also brand names for semaglutide, they are primarily approved for treating diabetes, with different dosing regimens than Wegovy.
Effectiveness of Semaglutide for Weight Loss
Studies have consistently demonstrated the effectiveness of semaglutide in promoting weight loss when combined with lifestyle modifications. A 2021 study showed that half of the participants experienced an average weight loss of 15% or more, equating to an average 35-pound weight loss over 68 weeks. Semaglutide has also shown more significant weight loss compared to other GLP-1 RAs like liraglutide.
Safety and Side Effects of Semaglutide
The most common side effects reported in clinical studies are nausea and vomiting, with gradual dose increases helping to reduce these effects. Other potential side effects include diarrhea, constipation, abdominal pain, headache, fatigue, and dizziness. Although rare, acute pancreatitis and gallbladder disorders can also occur. Animal studies have suggested a potential link between semaglutide and thyroid cancer, leading to a recommendation against its use in individuals with a history of medullary thyroid carcinoma.
Semaglutide for Weight Loss in Hypothyroidism: Limited Research
Currently, no specific studies have focused on using semaglutide for weight loss in individuals with hypothyroidism. However, semaglutide has consistently demonstrated its effectiveness in causing weight loss in patients with or without diabetes by reducing appetite and caloric intake.
Important Considerations for Semaglutide Use
It's crucial to address the foundations of health, such as diet and lifestyle changes, before considering medications like semaglutide for weight loss, especially in the context of hypothyroidism. Reducing inflammation and implementing a whole-foods-based diet can be beneficial.
Practical Guidance for Patients with Hypothyroidism Considering Ozempic
For most adults with primary hypothyroidism managed with levothyroxine, Ozempic is not automatically off-limits. The main warning is for individuals with a personal or family history of medullary thyroid carcinoma (MTC) or MEN-2.
Hypothyroidism Alone is Not a Contraindication
The FDA prescribing information only lists MTC, MEN-2, and prior serious hypersensitivity as absolute disqualifiers.
Weight Loss May Lower Levothyroxine Dose
A 10 kg weight drop can decrease the daily T4 replacement dose. Regular TSH re-testing after each Ozempic dose increase is essential to prevent over-replacement.
Semaglutide Has No Direct Effect on Thyroid Hormone Conversion
It acts on GLP-1 receptors in the gut and brain and doesn't alter peripheral deiodinase activity.
Stagger Dosing to Protect Levothyroxine Absorption
Take levothyroxine, wait at least 30â60 minutes, and then administer Ozempic later in the day to avoid any drop in thyroid-hormone uptake.
Recognizing Warning Signs
Seek immediate care if neck swelling or dysphagia appears. Persistent hoarseness longer than 2 weeks requires laryngoscopy. Unexplained diarrhea plus weight loss could indicate hyperthyroidism. Severe fatigue despite normal glucose merits a TSH check. New shortness of breath without a lung cause is a thyroid red flag.
Will Ozempic Change How You Take Your Daily Levothyroxine Tablet?
Inject Ozempic at least 2 hours after swallowing levothyroxine. Split morning supplements away from both drugs. Use a consistent injection day to stabilize the gastric emptying pattern. Re-check TSH after introducing semaglutide.
Self-Care Steps to Keep Both Your Thyroid and Weight Loss on Track
Aim for 1.0â1.2 g of protein per kg of ideal body weight. Hydrate with at least 2 L of water daily. Add resistance training twice a week. Track resting heart rate weekly. Schedule routine thyroid lab checks while on GLP-1 therapy.
Labs and Medications to Review Before and After Starting Ozempic
Establish a baseline TSH, free T4, and anti-TPO antibodies. Aim for a TSH between 0.5â3.0 mIU/L before adding Ozempic. Detect semaglutide's LDL drop with a fasting lipid panel. Clarify glucose benefit with HbA1c. Review other gastric-emptying drugs like opioids. Document kidney and liver function at baseline and during therapy.
GLP-1 Receptor Agonists and Thyroid Function: A Deeper Dive
The increasing use of GLP-1 RAs in managing type 2 diabetes mellitus has raised interest regarding their impact on thyroid function. While these agents are well-known for their efficacy in glycemic control and weight management, their association with thyroid disorders requires clarification due to the complex interplay between thyroid hormones and metabolic pathways.
Thyroid Dysfunction and Diabetes Mellitus
Thyroid dysfunction and diabetes mellitus are conditions frequently seen in clinical practice and often coexist. Both hyperthyroidism and hypothyroidism are more common in patients with T2DM compared to those without diabetes. Studies have shown a significantly higher prevalence of thyroid dysfunction among patients with T2DM compared to the general population.
Potential Mechanisms Linking T2DM and Thyroid Cancer
Insulin resistance, dysglycemia, high body mass index (BMI), and hypertension significantly increase the incidence of thyroid cancer. Hyperinsulinemia can reduce cell apoptosis and induce cell proliferation through insulin and the insulin-like growth factor-1 (IGF-1) pathway. Insulin receptors are overexpressed in most thyroid tumors as an early step in thyroid carcinogenesis.
How GLP-1 RAs Work
GLP-1 RAs exert their effect on glucose control through multiple mechanisms based on the incretin effect. GLP-1 facilitates insulin secretion. GLP-1 generates physiological responses by binding with GLP-1R, which is located on specific target cells. The stimulation of GLP-1R initiates an intricate intracellular signaling cascade, culminating in the activation of the protein kinase A (PKA) pathway through the generation of cyclic adenosine monophosphate (cAMP).
GLP-1R Distribution in Various Tissues
In addition to the pancreas, GLP-1R is distributed in various tissues, including the lungs, kidneys, central nervous system, stomach, cardiomyocytes, and vascular endothelial cells. Some studies have demonstrated the presence of GLP-1R in hepatocytes, in thyroid cells, and in thyroid C cells.
GLP-1 RAs and Thyroid Cells: Research Findings
Studies examining the expression of insulin receptor (IR), IGF-1 receptor (IGF-1R), and GLP-1R in normal thyroid tissue, papillary thyroid carcinoma (PTC) tissues, and PTC cells have shown that all three receptors were detected in both PTC tissues and PTC cell lines, as well as in normal thyroid cells. GLP-1R was found to be overexpressed in human PTC tissues/cells. Researchers concluded that GLP-1 RAs may not influence cell proliferation or energy metabolism in PTC cells.
Another study investigated primary cultures of rat and human thyroid cells to assess the expression and function of GLP-1R in C cells. GLP-1R expression was observed in primary rat C cells but was not detected in primary human C cells. Stimulation with GLP-1 RAs resulted in a modest increase in calcitonin release and expression in primary rat thyroid cultures; however, no functional response to GLP-1 RAs was observed in human thyroid cultures.
GLP-1 RAs and Weight Loss: Clinical Evidence
Numerous studies have investigated the impact of GLP-1 RAs on body weight. A meta-analysis evaluating the efficacy of 16 different GLP-1 RAs concluded that the combination of cagrilintide and semaglutide was the most effective in reducing body weight. Another systematic review suggests that semaglutide induces a weight reduction of approximately 1â2% every 10 weeks in patients with T2DM and is more effective than other GLP-1 RAs, with the exception of tirzepatide.
Safety and Tolerability of GLP-1 RAs
The adverse effects associated with GLP-1-based therapies predominantly manifest in the gastrointestinal tract with symptoms such as nausea, vomiting, and diarrhea. However, these effects seem to primarily range from mild to moderate severity, with a tendency to diminish over time.
Study Links GLP-1s and Reduced TSH Levels After Weight Loss
Patients with a history of hypothyroidism who were prescribed a glucagon-like peptide (GLP)-1 medication and lost more than 5 pounds saw a reduction in their thyroid-stimulating hormone (TSH) levels, according to a study conducted by Epic Research. Additionally, those who gained weight had no statistically significant change in their TSH levels.
The Impact of Weight Loss on Thyroid Hormone Homeostasis
A 2014 study demonstrated that moderate dietary restriction resulted in weight loss, and T3 decreased significantly in the absence of significant changes in TSH or free T4. Additionally, the T3 to free T4 ratio decreased significantly in those who lost more than 5% of their body weight.
GLP-1 Medications and TSH Levels: A Closer Look
Patients who were prescribed semaglutide and lost over 5 pounds saw the greatest reduction of their TSH levels. Semaglutide had different effects in the "lost 0 to 5 pound" group and weight gain group, demonstrating TSH changes of -0.27 mU/L and 0.04, respectively.
GLP-1 Medications and Thyroid Dysfunction: Conflicting Results
A June 2024 review aimed to find a deeper understanding of GLP-1 medicationsâ interactions with thyroid dysfunction and confirmed an interaction between thyroid dysfunction and metabolic conditions. They suggested that thyroid function tests in routine screening of patients with diabetes should be performed, particularly on those who are being treated with GLP-1 medications.
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