Tirzepatide vs Semaglutide for Weight Loss: Which is Better?

Two drugs show promise in the field of weight loss and diabetes management—Tirzepatide and Semaglutide. How well do they fare if they’re stacked up together? This guide will discuss the mechanisms, efficacy, side effects, and costs of Tirzepatide vs Semaglutide.

What Is Tirzepatide?

Tirzepatide is a new medication that caught the attention of medical professionals because of the dual action it exerts in managing blood glucose levels as well as weight. The Tirzepatide brand name is Mounjaro—and it has been around since May 2022 and approved by the Food and Drug Administration (FDA) in the treatment of type 2 diabetes mellitus (T2DM). The drug is injectable and the dosing is once a week. Its function is similar to the two hormones that control appetite and blood sugar namely—glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP). The dual function sets Tirzepatide apart from other treatments available. According to a study in 2023, the drug significantly reduces weight in patients with type 2 diabetes and those with obesity, which makes it a promising therapy for weight loss. And, apart from its potential to be a therapeutic regimen for weight loss, it also showed significant reduction in blood sugar.

What Is Semaglutide?

Semaglutide is a GLP-1 receptor agonist that has been approved by the FDA marketed as Ozempic, Wegovy, and Rybelsus. It has been around a bit longer in comparison, but has been popular in the treatment of diabetes. It targets only the GLP-1 pathway in lowering the blood sugar levels as well as reducing the appetite. It is also available as an injection once a week and efficient in glycemic control and weight loss.

The Rybelsus is an oral tablet approved as a supplement to exercise and diet particularly in improving glycemic control of adults with T2DM. Ozempic, on the other hand, is an injectable and approved only for T2DM glycemic control.

Wegovy is also offered as a subcutaneous injection, and has been approved for chronic weight management as a therapy supplementary to reduced-calorie diet and increased physical activity for patients with obesity—particularly those whose BMI is > 30 kg/m² or overweight at BMI > 27 kg/m². However, an additional requirement for its use in such patients is the presence of at least one weight-related comorbid condition, such as T2DM or dyslipidemia.

Mechanism of Action

The way medications work once inside the body will determine how effective it is—Tirzepatide vs Ozempic (Semaglutide) have distinct mechanisms that make them highly efficient.

Differences in Their Mechanisms

Both Tirzepatide and Semaglutide target the GLP-1 receptor—Ozempic’s mechanism of action functions similarly to the naturally-occurring GLP-1 hormone: It activates GLP-1 receptors in the gut, brain, and pancreas. Generally, the Semaglutide mechanism of action involves the activation of the GLP-1 receptor, which improves insulin secretion in response to increased blood glucose levels. It also slows down emptying of the stomach, boosts cell proliferation in the pancreas, and reduces appetite.

Meanwhile, Tirzepatide targets an additional receptor other than the GLP-1—the GIP receptor, which not only stimulates insulin release, but is also involved in fat metabolism, thus potentially offering more significant weight loss benefits. When compared to the GLP-1 agonist, the resulting effect from GIP receptor stimulation seems to be more impactful. According to a study in 2021, a weekly dosing of 5-15 mg of Tirzepatide significantly reduced body weight by 16.5% to 22.4% in more than 72 weeks of treatment in a non-diabetic patient.

Clinical trials have compared the performance of each drug in terms of weight loss and glycemic control.

Studies and Trials Comparing Tirzepatide and Semaglutide

There have been multiple studies that have been done to compare the efficacy of Tirzepatide and Semaglutide. A prominent trial includes the SURPASS-2 study, where Tirzepatide demonstrated superior efficacy over Semaglutide in a 40-week phase 3 trial. Participants in this trial who were treated with Tirzepatide experienced more reductions in their glycated hemoglobin (HbA1c), which is a key marker used in measuring long-term blood sugar control.

Results on Weight Loss

Recent studies have highlighted the impressive impact of Tirzepatide on weight loss, which surpassed the effects of Semaglutide. In a 2022 clinical trial, it showed that participants receiving the highest allowable dose of Tirzepatide have experienced a significant body weight reduction by 22.5% from their initial weight. This result is significantly higher than the weight loss observed in Semaglutide exhibited in the STEP trial, where patients lost about 15% of their initial body weight. These findings suggest that Tirzepatide may be a more potent option for individuals whose goal is to lose weight.

Results on Glycemic Control

Both Tirzepatide and Semaglutide are effective in controlling blood glucose levels, but studies have shown Tirzepatide to have superior results due to its dual action on GLP-1 and GIP receptors. This dual action provides a more substantial reduction in HbA1c levels, positioning Tirzepatide as a strong option for patients with type 2 diabetes by potentially enhancing insulin secretion and lowering glucagon levels for better glycemic control. Moreover, Tirzepatide has demonstrated significant benefits in weight reduction, a critical factor in managing type 2 diabetes.

Side Effects

No medication has been formulated without side effects. Knowing the risks associated with every medication is crucial when making an informed decision.

Common Side Effects of Tirzepatide

Tirzepatide for weight loss has a dual action on GLP-1 and GIP receptors as previously mentioned, and may have different side effect profiles compared to Semaglutide. Some patients have reported more pronounced gastrointestinal symptoms with this drug, especially during the early phases of treatment. The common side effects of Tirzepatide include the following:

• Nausea

• Diarrhea

• Decreased appetite

• Vomiting

• Constipation

Common Side Effects of Semaglutide

On the other hand, Semaglutide has been known to be associated with the risk of developing gallbladder issues and the potential to increase the heart rate, although these are side effects that are relatively uncommon. However, common side effects of Semaglutide include the following:

• Nausea

• Vomiting

• Diarrhea

• Abdominal pain

• Constipation

Comparison of Side Effect Profiles

Both Tirzepatide and Semaglutide share common profiles for their side effects typical of incretin-based therapies, which is relatively limited to gastrointestinal symptoms, such as nausea, vomiting, constipation, or diarrhea. Most of these tend to be mild to moderate in severity and are closely related to dose increases. Additionally, they usually resolve over time as the body adjusts to the new dosage. .

Dosage and Administration

This section will provide clear and concise guidelines on how to correctly use the medication in question.

Recommended Dosages for Tirzepatide

For both weight loss purposes and T2DM treatment, Tirzepatide is usually started on a low dose with gradual, incremental increase to minimize the side effects. The typical dosing regimen for the Tirzepatide injection is as follows:

The administration route for Tirzepatide is subcutaneous (SQ) once weekly dosing and the usual parameters to monitor its efficacy are the HbA1c levels as well as the body weight. Adverse effects are usually monitored as well. Note: If there is a missed dose, the administration of it should be within 4 days, but if not possible, it is important to skip the missed dose and return to the original schedule. Please refer to the instructions given by your physician.

Recommended Dosages for Semaglutide

Semaglutide also has similar titration schedule to minimize the risks of side effects and the typical picture of the regimen is as follows:

The administration of Semaglutide is through SQ injection on the abdomen, thigh, or upper arm. It is important to rotate the injection sites within the same body region so as to prevent injection on the same site each week.
Note: Do not mix Semaglutide and insulin directly (if you have insulin as a medication) and in case of missed dose for T2DM, it must be administered promptly within 5 days. However, if the duration of the missed dose is more than 5 days, the dose should be skipped and the regular schedule is resumed. For weight management, if the next scheduled dose is more than 2 days away, administer the skipped dose. If the next schedule is less than 2 days away, skip the dose and resume the normal schedule. Please follow the specific instructions given by your physician.

Differences in Administration and Patient Compliance

The administration of both Semaglutide and Tirzepatide are administered through SQ injections once weekly, but patient compliance may vary due to several factors including:

• Side Effect Profile and Ease of Use: If the drug has fewer or more tolerable side effects, patients tend to stick with the treatment regimen as opposed to the drug that has substantial side effect profiles.

• Market Presence and Guidelines: Some patients may choose Semaglutide because it has been in the market far longer than the newer Tirzepatide, which means they also have established guidelines. This track record may entice patients into feeling more comfortable with the medication and may improve patient compliance.

Potential for Greater Weight Loss Benefits: Tirzepatide has greater weight loss benefits, which may be more appealing to patients.

Cost Comparison

A major deciding factor for most patients when it comes to choosing a medication, particularly in long-term management, is the cost. For this reason, we will touch upon the average cost of these treatments in order to give you an idea about what to expect in that regard.

Average Cost of Tirzepatide Treatment

Weight loss regimen is not without catch—the catch? It is expensive, particularly in the case of Tirzepatide, being newer in the roster of weight loss management drugs. The average monthly cost may range from $1,000-$1,200 considering that for every 2 milliliters it costs about $1,134.

Average Cost of Semaglutide Treatment

On average, Semaglutide generally costs around $700 to $1500 per month, depending on the dosage, brand, and how it is going to be used. For T2DM treatment, the cost for every 3 milliliters is at $1,029, which is around $686 per month for three months. However, for Semaglutide weight loss regimen, the price per month increases to around $1,430 per month.

Impact of Cost on Patient Choice

According to a study in 2023, the treatment with once-weekly Tirzepatide 10 mg demonstrated a much higher cost but also a greater reduction in HbA1c, as well as superior weight loss when compared to 1 mg of Semaglutide after 52 weeks. It was also found that the incremental cost-effectiveness ratio for Tirzepatide vs Semaglutide reaches $2,247 per 1% reduction of HbA1c and $237 per weight loss of 1 kg. Based on this information, the cost of each medication will directly influence the patient’s choice.

Final Thoughts

Both Tirzepatide and Semaglutide are powerful tools in the fight against obesity and type 2 diabetes. Tirzepatide may offer greater weight loss and slightly better glycemic control, but at a higher cost and with potentially more side effects. Semaglutide remains a reliable and slightly more affordable option with a well-established safety profile. Ultimately, the choice between these medications should be made in consultation with a healthcare provider, considering the individual’s specific needs, tolerance, and financial situation.