You've probably heard of tirzepatide and semaglutide, as these medications have become very popular for the management of both diabetes and obesity. Choosing between these medications and knowing which one is best to manage your condition can be a challenge.
GLP-1 receptor agonists are a drug class approved for managing type 2 diabetes. Several of them have also been approved to treat obesity. This class of medications has opened new avenues for diabetes management and is among some of the more effective medicines for treating obesity.
This guide comprehensively compares tirzepatide and semaglutide, including benefits, mechanisms, side effects, and cost considerations.
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Overview of Tirzepatide and Semaglutide
Tirzepatide and semaglutide are commonly prescribed medications for diabetes management and the treatment of obesity.
What Are They?
Tirzepatide is marketed under the brand name Mounjaro for diabetes and Zepbound for obesity and obstructive sleep apnea (OSA).
Tirzepatide works on glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. This combination medication is the first medication in its class.
Tirzepatide is a second-line medication for the treatment of diabetes, meaning that it is usually used if another medication is not effective.
Semaglutide is sold under the brand name Ozempic for type 2 diabetes and the reduction of risk for major adverse cardiovascular events and Wegovy for obesity.
Semaglutide is a GLP-1 receptor agonist. It is also available as an oral medication under the brand name Rybelsus for type 2 diabetes.
Semaglutide was first approved for the treatment of diabetes in 2017. It was then approved for chronic weight management in 2021 and placed on the drug shortage list in 2022.
Tirzepatide was initially approved in 2022 for diabetes. In 2023, it was also approved to treat obesity and weight-related medical problems.
Recently, in 2024, tirzepatide received approval for treating moderate to severe obstructive sleep apnea in adults with obesity.
How Do They Work?
GLP-1 receptor agonists stimulate insulin secretion in response to glucose through the incretin pathway. They act on the GLP-1 receptor and, through its activation, decrease glucagon production and increase insulin production.
In addition, they promote weight loss by decreasing appetite and slowing the rate at which the stomach empties. GLP-1 medications also show potential benefits for other diseases, such as cardiovascular disease.
Tirzepatide is unique because it acts on GIP receptors in addition to its GLP-1 receptor agonist effects. This dual mechanism of action decreases appetite and blood glucose levels more than medications that act solely on the GLP-1 receptors.
Clinical trials have observed these effects, but they may vary depending on individual factors. Consult a healthcare provider for personalized advice.
Effectiveness in Diabetes Management
Both tirzepatide and semaglutide are effective medications for diabetic management.
Clinical Trial Results
Clinical trials for semaglutide have shown a decrease in hemoglobin A1c of 1.2-2.2%, depending on the dose.
Additionally, studies have shown significant benefits in cardiovascular outcomes for patients at a high risk for poor cardiovascular outcomes. There is an improvement in the risk of cardiovascular death, nonfatal heart attacks, and nonfatal stroke.
Clinical trials for tirzepatide have shown a decrease in hemoglobin A1c of 1.87-2.59%, depending on the dose.
Additionally, tirzepatide has been shown to decrease the apnea-hypopnea index by 20-29.9 events per hour.
Head-to-head studies suggest tirzepatide provides comparable or more significant reductions in hemoglobin A1c compared to semaglutide at 40 weeks for all doses.
Impact on Weight Loss
Tirzepatide and semaglutide are both approved for the treatment of obesity and overweight, in addition to their indication for diabetes.
Studies have shown that semaglutide results in a mean weight loss of 14.9% of total body weight. At 68 weeks, the body weight decreased by 15.3 kg, substantially more than the placebo.
Tirzepatide showed a mean total body weight decrease of 15% at 72 weeks.
Comparing tirzepatide and semaglutide in head-to-head comparisons, a 2024 study published in JAMA showed that most people had a weight loss of at least 5%, and tirzepatide showed greater weight loss benefits.
Side Effects and Safety Profiles
The GLP-1 medications are associated with many positive outcomes but are also associated with side effects.
Common Side Effects
Side effects of semaglutide may include:
- Belching
- Bloating
- Change in taste
- Constipation
- Diarrhea
- Dizziness
- Excessive gas
- Fatigue
- Fever
- Hair loss
- Headache
- Heartburn
- Low blood sugars
- Nausea and vomiting
- Skin changes or pain at the injection site
- Shakiness
- Stomach pain
- Weakness
- Yellowing of the skin or eyes
Tirzepatide is also associated with side effects. Some of these include:
- Dehydration
- Eye problems
- Gallstones or gallbladder inflammation
- Injection site reactions
- Low blood sugar
- Nausea and diarrhea (up to 10% of the time)
- Pancreatitis
- Rapid heart rate
Rapid and excessive weight loss can also have side effects on your body. In addition to fat loss, rapid weight loss will decrease metabolism and can result in the loss of muscle mass.
Muscle loss can further decrease your metabolism due to muscle calorie-burning effects. Other side effects associated with rapid weight loss include:
- Decreased immune system
- Electrolyte imbalances
- Fatigue
- Hair loss
- Inadequate nutrients
- Loss of bone density
- Loss of strength/muscle
Side effects are one of the reasons that many people may stop using semaglutide, tirzepatide, and other GLP-1 medications. The discontinuation rate is as high as 36.5% at 12 months.
Patients should review potential risks and benefits with their healthcare provider to determine whether these medications suit their health needs.
Long-Term Safety Concerns
GLP-1 medications are generally considered safe for long-term use.
There are concerns for pancreatic and thyroid cancer, but researchers have been unable to find a definitive link between the medications and these conditions due to the infrequency with which these conditions occur. There is limited long-term data for tirzepatide.
Some populations should not take semaglutide or tirzepatide and similar medications. These medications are not recommended for use in people who are pregnant or trying to get pregnant.
A study in BMJ Open showed no evidence of harm from GLP-1 medications in early pregnancy, but there is some evidence that GLP-1 medications may affect fetal growth.
The American Board of Obesity Medicine recommends stopping these medications at least 2 months prior to getting pregnant.
Other groups that should avoid GLP-1 medications include those with:
- A history of pancreatitis or pancreatic cancer
- Acute gallbladder disease
- A family or personal history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN2)
People with a history of suicide attempts or active suicidal thoughts may want to avoid the medication due to mixed data on whether this medication could increase suicidal ideation.
Cost and Accessibility
If you think that semaglutide or tirzepatide are medications that could benefit you, one of the things you may wonder about is the cost and whether you have access to these medications.
Pricing Comparison
Name-brand semaglutide costs between $1000 and $1500 per month without insurance. No generic FDA-approved version of the medication is currently available, but some compounding pharmacies may offer non-FDA-approved versions at a lower cost.
Tirzepatide costs around $1000-$1200 without insurance. Like semaglutide, no generic FDA-approved medication exists, but compounded medications may be available.
Insurance coverage for these medications can vary. Many insurance companies exclude medicines for treating obesity.
GLP-1 medications may be better covered for treating Type-2 diabetes and other medical conditions. Talk to your insurance provider to find out if your company covers these medications.
Accessibility Challenges
Access to GLP-1 medications has been challenging for several years. There have been shortages, making it difficult for patients to get a consistent supply.
Even if people can get insurance coverage or have the ability to buy the medication out-of-pocket, they may not be able to get the prescription filled due to the shortages.
Key Considerations for Choosing the Right Medication
Both semaglutide and tirzepatide are effective for managing diabetes and obesity as chronic diseases. Choosing which medication to use can be a challenge, as various factors must be considered.
Personalized Factors
Tirzepatide may be the right choice if you have obstructive sleep apnea or a higher hemoglobin A1c.
Semaglutide may be a better choice for people with heart disease. Your provider can help determine which medication is right for you based on your health history, risk factors, insurance coverage, and other financial factors.
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Key Takeaways
- Both semaglutide and tirzepatide have indications for management of diabetes and obesity.
- Tirzepatide is an additional indication for the treatment of obstructive sleep apnea.
- Semaglutide has additional indications for cardiovascular disease.
- GLP-1 medications are not recommended for use in breastfeeding or pregnancy.
- Insurance coverage is a challenge for many people seeking management of obesity.
- Ultimately, which medication you choose should be determined through a discussion between you and your healthcare provider.
- To learn more about GLP-1 medications or managing your healthcare conditions, consult your healthcare provider today.
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