New weight loss medications, including semaglutide (Ozempic, Wegovy) and tripeptide (Mounjaro), were originally developed for diabetes and became best-seller drugs for their remarkable efficacy and weight loss. Yet many people taking these endure severe side effects, especially when taken with other medications. Some individuals may develop serious complications. That’s why it’s essential to understand the long-term health risks of using these weight loss medications known as GLP1 agonists, hopefully avoiding unpleasant complications and negative impacts on other medicines you might be taking.

Medication and health risks of weight loss drugs

You’ve probably heard that despite the slimming effect, rapid weight loss treatments can have side effects such as gastrointestinal discomfort, mood changes, and skin appearance alterations. Additionally, changes in hormone levels and liver function associated with weight loss can significantly impact metabolism and dosage for other medications you may be taking. This article outlines medical complications that can arise from taking Ozempic, Mounjaro, or other GLP1 agonists and ways to reduce your risk.

Impact on organs and certain cancers

The new weight loss drugs work by stimulating glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) that regulate the neuroendocrine system functions, including appetite. These drugs can enhance function in the pancreas, thyroid, and other cells with these receptors, including some cancer cells, which have faster growth if they can express these proteins. Therefore, drug labels for semaglutide (Ozempic, Wegovy) and tripeptide (Mounjaro) warn not to prescribe these drugs for people with a personal or family history of medullary thyroid carcinoma (MTC), Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). It’s worth noting that GLP-1 agonists decrease the risk of colorectal cancer more than other antidiabetic therapies.

Bowel and pancreatic complications

When researchers compared the incidence of serious health complications of GLP-1 agonists versus bupropion-naltrexone (Contrave), another commonly used weight loss drug, it was found that semaglutide and tripeptide drastically increased the risk of

• pancreatitis – 9 times compared with “baseline”
• bowel obstruction – 4 times increased risk
• delayed stomach emptying (gastroparesis) – 3.6 times increased risk

Your DNA, diet, and lifestyle also directly affect the risk of pancreatitis and bowel obstruction. Consumption of alcohol, spicy foods, or smoking are known pancreatitis risk factors – avoiding these risk factors can make GLP1 treatment safer for you. However, individuals with specific genetic variations in PRSS1 and CFTR1 genes are at elevated risk of pancreatitis and should consider alternative weight loss treatments.

Actions you can take to minimize bowel issues

If you experience bloating and bowel obstruction, there are some steps you can take to alleviate the symptoms. Incorporating high-fibre foods with healthy oils, staying hydrated, practicing yoga, and doing exercises that stimulate bowel movements can also be helpful. However, if you are dealing with chronic constipation, you may need additional interventions. In such cases, it is important to seek medical help, especially if you experience severe abdominal pain, fever, vomiting, or other severe gastrointestinal symptoms. It is also important to inform your healthcare provider that you are taking a weight loss drug to ensure effective treatment.

Be aware: Surgeries and medical procedures under anesthesia

If you take medications such as Ozempic, Wegovy, or Mounjaro, you should talk to your doctor at least a week before any procedures requiring deep sedation, such as surgeries or colonoscopies. An empty stomach before these procedures is crucial, which means not eating or drinking for at least 16 hours beforehand. Any remaining food or liquid in the stomach can increase the risk of aspiration and other complications. However, GLP1 agonists can slow down stomach emptying, so it may be necessary to stop taking these medications for a few days (or a week for patients on weekly injections) before anesthesia. Inform your surgeon and anesthesiologist ahead of time about your weight loss medications and follow your doctor’s instructions to ensure a safe and successful procedure.

Important to note for colonoscopy and GI surgery

It is a well-known fact that GLP1 agonists can cause delayed intestinal transit. This can lead to inadequate gut emptying or cleansing before a colonoscopy or GI surgery, which often results in the need for a repeat procedure within a year. However, you can easily avoid this unnecessary and unpleasant experience by suspending the use of weight loss drugs such as Ozempic, Wegovy, or Mounjaro and paying extra attention to your diet and cleansing protocol before the procedure.

Gut motility and weight loss impact other medications

Because these weight loss drugs are complex molecules not metabolized by liver enzymes, semaglutide and tripeptide have few drug-drug interactions. However, rapid changes in body weight can drastically affect the dosing of many medications. Synthroid (levothyroxine) is especially sensitive to body weight, and GLP1 agonists have direct hormonal effects on the thyroid, requiring careful monitoring and levothyroxine dosage adjustment.

Rapid weight loss and hormonal rebalancing after bariatric surgery can alter the activity of liver enzymes that metabolize over 80% of drugs. Weight loss, inflammation and other factors can significantly increase the activity of CYPC9 and CYP2B6 liver enzymes. Depending on your genetics for these enzymes, you may need a higher dose of chronic medications such as NSAIDs, blood thinners, epileptic medications (metabolized by CYP2C9), bupropion, or HIV medications (metabolized by CYP2B6).

Population studies flagged an increased risk of suicidal ideation in people receiving therapy with these weight loss medications, triggering FDA and European regulators to investigate these reports. It is not yet clear if the increased risk of depression is due to the direct effect of GLP1 agonists or through the diminished effectiveness of antidepressants.

Special considerations

For women of reproductive age

The effectiveness of medications is impacted by hormonal changes, especially in women of reproductive age and in peri-menopause. Weight loss drugs are known to reduce the effectiveness of contraceptives – that’s how the term “Ozempic” or “Mounjaro babies” came about. Weight loss drugs can improve symptoms of polycystic ovary syndrome (PCOS) and fertility. These changes may catch women who had difficulty conceiving off-guard. However, some forms of contraception, especially hormonal patches, might be ineffective due to the accelerated clearance of these medications. Mounjaro carries a warning about the reduced effectiveness of birth control pills. Other forms of contraception, such as IUDs, may be more effective for birth control in women taking weight loss drugs.

Eye disease in people with diabetes

Although clinical trials have shown that GLP1 agonists reduced HbA1c levels and reduced the incidence of stroke and heart complications, they do worsen the risk of diabetic retinopathy (DR). People with diabetes should be aware of this significant issue and must undergo regular eye exams. If early signs of eye disease are identified, a switch to alternative diabetic medication is recommended.

Summary

• Ozempic, Wegovy, Mounjaro and other GLP1 agonists are effective diabetes and weight loss medications that share common side effects and complications.
• Dietary counselling, physical exercise, and a healthy lifestyle are essential for achieving the best results and mitigating medication-induced complications.
• Special considerations and treatment discontinuation are required before surgery, colonoscopy or another serious medical procedure performed under anesthesia.
• Weight loss medications can impact the effectiveness of contraceptives and many other drugs – consult with your doctor and pharmacist regularly to adjust medications’ dosing as your body changes.
• A regular eye examination is vital for people with diabetes.
• Alternative diabetes and weight loss therapy should be considered for people with a personal or family history of pancreatitis, thyroid cancer or diabetic retinopathy.

Selected References

Yao R et al., EFFECT OF GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS ON BOWEL PREPARATION FOR COLONOSCOPY The American Journal of Gastroenterology, October 19, 2023. DOI: 10.14309/ajg.0000000000002564

Sodhi M et al., Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss JAMA. 2023;330(18):1795-1797. doi:10.1001/jama.2023.19574

Liz Scherer: Caution Urged for Obesity Drugs and Birth Control Pills Medscape Oct 18.2023

Ghasim H et al., Impact of Obesity and Bariatric Surgery on Metabolic Enzymes and P-Glycoprotein Activity Using the Geneva Cocktail Approach J Pers Med. 2023 Jul; 13(7): 1042

Wang L et al., GLP-1 Receptor Agonists and Colorectal Cancer Risk in Drug-Naive Patients With Type 2 Diabetes, With and Without Overweight/Obesity JAMA Oncol. 2023 Dec 7: e235573. doi: 10.1001/jamaoncol.2023.5573