Does semaglutide cause cancer? An evidence-based guide
Could your weight loss or diabetes medication increase your cancer risk? Here’s a clear look at the evidence behind the warning.
Key highlights
- Semaglutide has a boxed warning for medullary thyroid carcinoma and MEN 2 syndrome, but human studies do not show any significant risk of these malignancies with semaglutide use.
- The FDA has issued these warnings based on rodent studies where GLP-1 medications caused hyperplasia of medullary C-cells, leading to medullary C-cell carcinoma.
- Large-scale clinical trials and real-world studies do not show any strong association between cancer and semaglutide use.
- Research studies indicate that semaglutide protects against obesity associated cancers indirectly by promoting weight loss, improving metabolic health, and maintaining blood sugar levels.
- If you plan to start semaglutide, consult with a licensed healthcare provider for a personalized risk assessment. If you have a personal or family history of thyroid or neuroendocrine cancers, the medication is contraindicated for you.
If you are currently using or thinking about starting semaglutide treatment, whether Ozempic, Wegovy, or Rybelsus, you have probably heard a lot about cancer risk with semaglutide. You might wonder, can semaglutide really cause cancer, and if there is any clinical evidence of a correlation between cancer and semaglutide use.
The U.S. Food and Drug Administration (FDA) has a boxed warning for thyroid cancer and MEN 2 syndrome. However, there is no evidence-based human study showing any clear link between semaglutide and increased risk of cancer. Instead, clinical data show that semaglutide helps manage obesity, which reduces the risk of cancer. The FDA has issued these warnings based on rodent studies where semaglutide was linked to increased risk of thyroid cancer and MEN 2 syndrome.
There is no simple “yes” or “no” answer. This article will explore why the concern exists, the specific types of cancer involved, and how the medication may actually provide protective benefits against other cancers.
Understanding the FDA’s black box warning
Black box warnings, issued by the FDA, indicate the major risks associated with the medication. The black box warning for semaglutide is based on animal studies where rats and mice developed thyroid tumors, including a rare type of thyroid cancer called medullary thyroid carcinoma (MTC).
Although no human studies have indicated an increased risk of cancer with semaglutide, the FDA mandates a boxed warning based on any concerning animal data to ensure utmost caution.
In rodents, semaglutide activates GLP-1 receptors in the thyroid, which stimulates calcitonin release, upregulates expression of the calcitonin gene, and causes hyperplasia of C-cells. Hyperplasia or C-cell overgrowth increases the risk of thyroid cancer in rodents.
In comparison, humans have a few GLP-1 receptors in thyroid C-cells, and GLP-1 receptor agonists like semaglutide do not activate calcitonin release or cause thyroid cancer. A research study shows that patients taking a GLP-1 medication (liraglutide) did not show high calcitonin levels after 2 years of taking the medication. Instead, calcitonin levels remained at the lower end of the normal range. These results indicate that GLP-1 (glucagon-like peptide-1) agonists are less likely to cause thyroid cancer in humans compared to rodents.
However, due to the FDA’s warning, semaglutide is not recommended for individuals with a personal or family history of medullary thyroid carcinoma (MTC) or a rare genetic disorder called multiple endocrine neoplasia syndrome type 2 (MEN2).
What large-scale clinical trials reveal: No proven cancer risk
Extensive human clinical trials, including the STEP (weight management) and SUSTAIN (type 2 diabetes) clinical trials, were conducted before the approval of Ozempic and Wegovy to assess the safety of these medications. Thousands of participants used semaglutide during these trials, but the risk of cancer was negligible.
The STEP and SUSTAIN trial data
In the STEP and SUSTAIN trials, the incidence of thyroid cancer was not higher in the semaglutide group compared to the placebo group. The following table shows the incidence of malignant tumors with semaglutide compared to the placebo in STEP trials:
| Trial | Semaglutide 2.4 mg | Comparator (Placebo / Liraglutide) |
|---|---|---|
| STEP 1 | 1.10% | 1.1% (Placebo) |
| STEP 2 | 1.20% | 2.0% (Placebo) |
| STEP 3 | 0.70% | 0.5% (Placebo) |
| STEP 4 | 1.10% | 0.4% (Placebo) |
| STEP 5 | 1.30% | 2.6% (Placebo) |
| STEP 8 | 2.40% | 2.4% (Liraglutide 3.0 mg) / 1.2% (Placebo) |
In the SUSTAIN 6 trial for Ozempic, the number of thyroid cancer cases was actually lower in the semaglutide group. The semaglutide group did not show any cases of medullary thyroid cancer. Additionally, only one case of pancreatic cancer was observed with semaglutide compared to 2 cases with the placebo.
Clinical trials are the gold standard evidence for drug safety in humans. Results from clinical trials of semaglutide show that semaglutide is safe and does not cause or increase the risk of cancer in humans.
SUSTAIN and PIONEER trials for semaglutide show the following results:
| Study Name | Participants (Semaglutide, Comparator) | Comparator Type | Reported Cancer cases (Semaglutide) | Reported Cancer cases (Comparator) |
|---|---|---|---|---|
| PIONEER 2 | 175, 175 | Empagliflozin | Pancreatic 0, Thyroid 0 | Pancreatic 0, Thyroid 0 |
| PIONEER 3 | 1,397, 1,392 | Sitagliptin | Pancreatic 1, Thyroid 0 | Pancreatic 1, Thyroid 0 |
| PIONEER 4 | 285, 284 | Liraglutide | Pancreatic 0, Thyroid 1 | Pancreatic 1, Thyroid 1 |
| PIONEER 7 | 253, 252 | Sitagliptin | Pancreatic 0, Thyroid 0 | Pancreatic 0, Thyroid 0 |
| PIONEER 9 | 146, 146 | Liraglutide | Pancreatic 0, Thyroid 1 | Pancreatic 0, Thyroid 0 |
| PIONEER 10 | 393, 392 | Dulaglutide | Pancreatic 0, Thyroid 1 | Pancreatic 0, Thyroid 0 |
| SURPASS 2 | 469, 468 | Tirzepatide | Pancreatic 0, Thyroid 1 | Pancreatic 0, Thyroid 0 |
| SUSTAIN 2 | 818, 818 | Sitagliptin | Pancreatic 0, Thyroid 1 | Pancreatic 0, Thyroid 0 |
| SUSTAIN 3 | 404, 405 | Exenatide | Pancreatic 0, Thyroid 0 | Pancreatic 0, Thyroid 0 |
| SUSTAIN 4 | 722, 721 | Insulin glargine | Pancreatic 1, Thyroid 0 | Pancreatic 0, Thyroid 0 |
| SUSTAIN 7 | 601, 600 | Dulaglutide | Pancreatic 0, Thyroid 1 | Pancreatic 0, Thyroid 1 |
| SUSTAIN 8 | 394, 393 | Canagliflozin | Pancreatic 0, Thyroid 0 | Pancreatic 0, Thyroid 0 |
| SUSTAIN 10 | 290, 291 | Liraglutide | Pancreatic 0, Thyroid 0 | Pancreatic 0, Thyroid 0 |
| SUSTAIN 11 | 874, 872 | Insulin aspart | All neoplasms 6 | All neoplasms 1 |
Beyond trials: What real-world evidence tells us
A systematic review included 37 randomized controlled trials and 19 real-world studies to assess the risk of cancer with semaglutide. This review indicates that semaglutide use is not associated with an increased risk of thyroid cancer or any other type of cancer.
The results of this review are as follows:
| Cancer Type | Participants (No. of RCTs) | Risk with Placebo | Risk with Semaglutide |
|---|---|---|---|
| Thyroid cancer | 11,823 (11 RCTs) | 0 per 1000 | 0 per 1000 |
| Pancreatic cancer | 9,945 (10 RCTs) | 1 per 1000 | 0 per 1000 |
| All neoplasms | 16,839 (21 RCTs) | 5 per 1000 | 5 per 1000 |
A closer look at semaglutide and specific cancer risk
Let’s explore whether semaglutide increases the potential risk of thyroid, pancreatic, and other cancers.
Thyroid cancer
Thyroid cancer is the primary area of concern, as semaglutide has a boxed warning for thyroid cancer. However, these warnings are based on rodent studies only.
A SUSTAIN 6 clinical trial was conducted to assess the safety and efficacy of semaglutide for managing cardiovascular diseases and type diabetes mellitus. Adverse events of the medication were also studied. No case of medullary thyroid carcinoma was reported with semaglutide or placebo.
A systematic literature review of semaglutide assessed the risk of thyroid cancer with Ozempic (semaglutide) for type 2 diabetes and obesity. Across 10 studies, the incidence of thyroid cancer was less than 1%, which suggests that there is no significant risk of thyroid cancer associated with semaglutide use in humans.
Pancreatic cancer
Early reports raised concerns that GLP-1 drugs, including semaglutide, might increase the risk of pancreatic cancer because some patients experienced pancreatitis (inflammation of the pancreas). However, these concerns have not been confirmed in human studies.
In the SUSTAIN-6 clinical trial, the incidence of pancreatic cancer was 0% and 0.1% with 0.5 mg and 1 mg semaglutide doses, respectively, compared to 0.2% with the placebo.
Data from multiple large-scale randomized controlled trials and meta-analyses have consistently shown no increase in pancreatic cancer incidence among people treated with semaglutide compared to placebo or other diabetes medications. For example, in the combined data from 10 major trials, the risk of pancreatic cancer in the semaglutide group was 0 per 1,000 people, compared to 1 per 1,000 in the placebo group. These findings provide strong evidence that semaglutide does not increase the risk of pancreatic cancer.
Other cancers
The current evidence does not indicate an elevated risk of other types of cancer, such as breast, kidney, and colorectal cancer, with semaglutide use for most people.
A small preclinical study showed semaglutide may stimulate growth in neuroendocrine tumors that express GLP-1 receptors. However, these effects are unknown in humans. As per the FDA’s recommendation, patients with neuroendocrine cancers or MEN2 syndrome should exercise caution.
| Cancer Type | Risk Reported | Summary |
|---|---|---|
| Thyroid (Medullary Thyroid Carcinoma – MTC) | Sigificant risk in Rodents, less than 1% risk in humans | Animal studies showed thyroid C-cell tumors in rodents, but large human clinical trials have not demonstrated an increased risk. The FDA includes a warning for individuals with a personal or family history of MTC or Multiple Endocrine Neoplasia type 2 (MEN2). |
| Pancreatic Cancer | Negligible | Multiple large-scale randomized controlled trials and meta-analyses have found no evidence of an increased risk of pancreatic cancer in people using semaglutide. Early concerns were linked to reports of pancreatitis, but these have not been supported by human data. |
| Colorectal and Obesity related cancer | Possible reduction | Some observational and emerging studies suggest that semaglutide and other GLP-1 drugs may lower the risk of certain cancers due to weight loss, improved metabolic health, and reduced inflammation, though more research is needed. |
| Neuroendocrine Tumors (NENs) | In Rodent studies only | Preclinical cellular studies have shown potential effects on neuroendocrine tumor cells, but there is no clinical evidence of increased risk in humans. Patients with a history of neuroendocrine tumors or MEN1 should use caution. |
| All Malignant Neoplasms (General) | No | Across more than 16,000 participants in the STEP and SUSTAIN trials, there was no overall increase in cancer incidence among semaglutide users compared to placebo. |
Who should be concerned about cancer risk on semaglutide?
Semaglutide is contraindicated in patients with a personal or family history of medullary thyroid cancer and MEN 2 syndrome.
People with a personal or family history of Medullary Thyroid Carcinoma (MTC) and MEN Syndrome
Medullary thyroid carcinoma is a type of tumor that develops in the thyroid gland (located in front of the neck, below your Adam’s apple). This tumor forms inside the medulla of your thyroid gland. Medulla contains parafollicular C cells. When these cells become malignant or cancerous, medullary thyroid cancer is formed.
MEN 2 syndrome, or multiple endocrine neoplasia type 2 syndrome, is a rare type of genetic disorder that affects the endocrine systems of the body, such as thyroid glands, adrenal glands, and parathyroid glands. It occurs due to the mutation of the RET gene. Affected glands produce high levels of hormones, which can cause kidney stones and high blood pressure. Additionally, MEN2 syndrome can increase the risk of pheochromocytoma, medullary thyroid carcinoma, and parathyroid cell cancer.
Semaglutide is not recommended for people with a personal or family history of MTC or those with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). This is the reason your doctor asks about your personal and family history before prescribing. If you have a history of thyroid cancer in your family, inform your doctor to avoid any complications.
When taking semaglutide, look for the following symptoms of thyroid tumors:
- A feeling of fullness or tightness in the throat
- Difficulty swallowing (dysphagia)
- Hoarseness or voice changes
- Enlarged lymph nodes in the neck
- Pain in the front of the neck that may radiate to the ears
- Persistent cough without respiratory tract infection
- Difficulty breathing or shortness of breath
Consult your doctor for a detailed evaluation if you experience these symptoms.
Can semaglutide prevent cancer?
Obesity and diabetes are major risk factors for many types of cancers, including colorectal, endometrial, pancreatic, liver, gallbladder, and breast cancer. Clinical studies show that 5% increase in body mass index (BMI) is associated with a 10% increased risk of cancer-related deaths. Obesity and diabetes cause hyperglycemia, which causes metabolic dysfunction, leading to the growth and proliferation of cancer cells.
GLP-1 receptors, including semaglutide, are effective for managing the triad of obesity, diabetes, and cancer. These medications maintain blood glucose levels, suppress appetite, enhance the sensitivity of insulin, and promote insulin release from beta cells of the pancreas. These effects promote weight loss and improve glycemic control and metabolism, which lowers the risk of obesity related cancers.
In a clinical study involving 1,651,452 patients with type 2 diabetes, semaglutide decreased the development of 10 out of 13 obesity-associated cancers, which include the following:
- Colorectal cancer
- Meningioma
- Endometrial cancer
- Gallbladder cancer
- Multiple myeloma
- Kidney cancer
- Ovarian cancer
- Pancreatic cancer
- Esophageal cancer
- Hepatocellular carcinoma
These results suggest that GLP-1 receptor agonists can protect against cancer.
Weighing the risks and benefits
Although there has been a lot of chatter about the potential link between semaglutide and thyroid cancer in humans, current clinical evidence does not confirm this association. In contrast, both obesity (BMI 30 or more) and type 2 diabetes are significant risk factors for several types of cancer.
Research studies show that losing as little as 5–10% of body weight can significantly reduce the risk of cancer. Semaglutide is FDA-approved for promoting weight loss, improving blood sugar control, and providing cardiovascular protection. Therefore, the proven cancer risk associated with obesity is substantial, but the potential cancer risk of semaglutide is still theoretical and unproven in humans.
Based on large-scale trials data, the health benefits of semaglutide outweigh the very low and unproven risk of cancer. If you plan to start your treatment with semaglutide, consult a licensed clinician for a personalized risk assessment and a detailed discussion to make an informed choice.
Frequently asked questions
Should I stop taking my semaglutide because of cancer fear?
No, do not stop taking a prescribed medication without first discussing your concerns with your doctor. The risk of cancer is negligible with semaglutide unless you have a personal or family history of thyroid cancer or MEN 2 syndrome. In any case, consult your doctor before stopping any GLP-1 medication, as abruptly stopping these medications can lead to adverse effects.
What symptoms of thyroid cancer should I watch for?
Watch for the following symptoms of thyroid cancer:
- A feeling of fullness or tightness in the throat
- Trouble swallowing (dysphagia)
- Hoarseness or persistent voice changes
- Pain in the front of the neck that may radiate to the ears
- Persistent cough not caused by a cold or infection
- Difficulty breathing or shortness of breath
- Enlarged lymph nodes in the neck
Remember, medullary thyroid carcinoma is very rare with semaglutide use. If you have any of these symptoms, consult a licensed healthcare provider to rule out other health conditions. Have regular follow-ups with your doctor for continuous monitoring and to prevent the risk of side effects.
Are there any ongoing studies?
Yes, the U.S. Food and Drug Administration is continuously monitoring the safety of these medications. Additionally, large and long-term studies are also ongoing to provide more definitive results about the correlation between semaglutide use and cancer.
Does this apply to all GLP-1 drugs?
Yes, the FDA’s black box warning for medullary thyroid carcinoma and MEN 2 syndrome applies to the entire class of GLP-1 receptor agonists, which include liraglutide (Saxeda and Victoza), dulaglutide (Trulicity), semaglutide (Ozempic, Rybelsus, and Wegovy), and tirzepatide (Mounjaro and Zepbound).
Can semaglutide cause thyroid cancer in humans?
Currently, the risk of thyroid cancer is negligible with semaglutide use, and there is no clinical evidence of a correlation of semaglutide with cancer development in humans. However, the FDA has still issued a warning based on rodent studies. This is why semaglutide is contraindicated if you have a personal or family history of medullary thyroid carcinoma or MEN2 syndrome.
Are overall cancer rates higher in GLP-1 users?
No, the overall cancer rates are not higher in GLP-1 users. Large systematic reviews and clinical trials show no significant increase in cancer risk with semaglutide use.
Do GLP-1s actually protect against cancer?
Yes, GLP-1 RAs (glucagon-like peptide-1 receptor agonists) may indirectly protect you against cancer. Obesity and diabetes are risk factors for cancer. GLP-1 medications promote weight loss, improve metabolism, and treat type 2 diabetes, which decreases the risk of cancer. Early data suggest that weight loss drugs like semaglutide decrease the risk of colorectal cancer.
Should I worry about neuroendocrine tumors?
If you have a personal or family history of any neuroendocrine tumor, you should be cautious about using semaglutide. Talk to your doctor before starting the medication, as cellular studies suggest that semaglutide may cause MEN 2 syndrome. Although human data are still lacking, the FDA does not recommend using the medication if you have a history of MEN 2 syndrome.
What to discuss with your doctor
You can discuss the following concerns with your doctor:
- “I’ve read about a thyroid cancer warning. What does that mean for me?”
- “Can we schedule baseline thyroid labs or ultrasounds?”
- “Given my personal/family cancer history, is semaglutide still right for me?”
- “How do the benefits of weight loss and glucose control compare with theoretical risks?”
- “What signs and symptoms should I look for while taking the medication?”
- “Is there any risk of MEN2 syndrome based on my history?”
Conclusion: Understanding the cancer risks of semaglutide
Although semaglutide has a boxed warning for thyroid cancer and MEN 2 syndrome, the warning is based on animal studies. No human studies have shown any proven cancer risk, and large-scale human data do not indicate any established link between semaglutide use and cancer.
Contrary to this, human data suggest that semaglutide may decrease the risk of obesity related cancers indirectly by improving body weight and metabolism. The risk of neuroendocrine tumor and medullary carcinoma with semaglutide is mainly hypothetical and still under investigation. However, semaglutide is currently contraindicated for patients with a personal or family history of medullary thyroid carcinoma (MTC) and MEN 2 syndrome.
There is no simple “yes” or “no” answer to this query. It’s a complex risk-benefit analysis that is unique to your health, your family history, and your goals. For most patients who do not have a specific family history of thyroid or neuroendocrine disorders, the proven health benefits of semaglutide appear to far outweigh a theoretical and unproven risk.
If you plan to start semaglutide treatment, consult a licensed healthcare provider. Have a detailed conversation and discuss your concerns and questions. Your doctor will help you make a more informed decision about whether semaglutide is safe for you after knowing your complete medical and family history.
