Tirzepatide Vs Semaglutide For Blood Sugar Control And Body Weight Loss

Abstract

Tirzepatide and semaglutide are glucagon-like peptide-1 (GLP-1) receptor agonists increasingly used for weight management in patients with obesity and type 2 diabetes. This article reviews the latest evidence comparing the efficacy and safety profiles of these medications for weight loss. Tirzepatide appears more efficacious than semaglutide at promoting weight reduction, likely due to its dual agonist activity on GIP receptors in addition to GLP-1 receptors. However, tirzepatide may carry a higher risk of certain adverse effects. Ultimately, both drugs represent valuable treatment options, and shared decision-making between clinicians and patients is recommended.

Background

Both tirzepatide and semaglutide have been shown to reduce weight in patients with type 2 diabetes, but their comparative value for money and efficacy in real-world settings are unclear. This study aims to compare the efficacy and safety of tirzepatide and semaglutide for weight loss in a real-world population of US adults with overweight or obesity initiated on tirzepatide or semaglutide formulations labelled for type 2 diabetes

Introduction

Tirzepatide and semaglutide are both used for weight management in patients with type 2 diabetes. Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist, which may provide an additional weight loss boost. Semaglutide is a GLP-1 receptor agonist that mimics the natural hormone GLP-1, making the body feel less hungry. Both medications have been shown to be effective for weight loss, but their comparative efficacy and safety are unclear.

Study Design, Protocol, Approvals And Consents

This study used a real-world setting to compare the efficacy and safety of tirzepatide and semaglutide for weight loss. The study population consisted of US adults with overweight or obesity initiated on tirzepatide or semaglutide formulations labelled for type 2 diabetes. The study used a propensity score matching approach to balance the baseline covariates between the two groups.

Inclusion And Exclusion Criteria

Patients were included if they were initiated on tirzepatide or semaglutide between May 2022 and September 2023, had no prior GLP-1 receptor agonist use, received regular care in the previous year, had a GLP-1 receptor agonist prescription written in the 60 days prior to initiation, and had an available baseline weight.

Discussion

The results of this study show that tirzepatide was significantly more effective than semaglutide in achieving weight loss. Patients on tirzepatide were more likely to achieve 5%, 10%, and 15% weight loss and experienced larger reductions in weight at 3, 6, and 12 months. The study also found that tirzepatide had a similar safety profile to semaglutide, with similar rates of gastrointestinal adverse events.

Objective

The objective of this study was to compare the efficacy and safety of tirzepatide and semaglutide for weight loss in a real-world population of US adults with overweight or obesity initiated on tirzepatide or semaglutide formulations labelled for type 2 diabetes.

Design/Methods

This study used a real-world setting to compare the efficacy and safety of tirzepatide and semaglutide for weight loss. The study population consisted of US adults with overweight or obesity initiated on tirzepatide or semaglutide formulations labelled for type 2 diabetes. The study used a propensity score matching approach to balance the baseline covariates between the two groups.

Tirzepatide vs Semaglutide Side Effects

Tirzepatide and semaglutide are both glucagon-like peptide-1 (GLP-1) receptor agonists used for weight loss and type 2 diabetes management. While both medications have similar mechanisms of action, they have distinct side effect profiles. The most common side effects of semaglutide are nausea, diarrhea, and constipation, whereas tirzepatide causes gastrointestinal side effects like vomiting along with an increased risk of hypoglycemia (low blood sugar). Both medications can cause mild to severe side effects, including gastrointestinal issues, hypoglycemia, pancreatitis, gallbladder disease, and renal impairment. Patients should maintain open communication with their healthcare provider to manage any adverse reactions and adjust treatment as necessary.

Tirzepatide vs Semaglutide Safety

Both tirzepatide and semaglutide have similar safety profiles, with common side effects including gastrointestinal issues like nausea, vomiting, diarrhea, and constipation. However, tirzepatide has been associated with a higher risk of some more serious side effects compared to semaglutide, including an increased risk of hypoglycemia (low blood sugar) and pancreatitis. Both medications also carry a boxed warning for the potential risk of thyroid C-cell tumors. Overall, while the side effect profiles are generally comparable, tirzepatide may have a slightly higher risk of certain adverse events, particularly at higher doses. Patients should discuss the potential risks and benefits of each medication with their healthcare provider to determine the best treatment option.

Tirzepatide vs Semaglutide Cost

Tirzepatide and semaglutide have similar costs for weight loss treatment, but tirzepatide may provide better value for money. A recent study calculated the cost needed to treat to achieve a 1% reduction in body weight using high-dose tirzepatide (15 mg) versus semaglutide (2.4 mg). The study found:

• Using tirzepatide resulted in a weight loss of 17.8% (95% CI: 16.3%-19.3%) compared with 12.4% (95% CI: 11.5%-13.4%) for semaglutide.
• The total cost of 72 weeks of tirzepatide was estimated at $17,527 compared with $22,878 for 68 weeks of semaglutide.
• The cost needed to treat per 1% of body weight reduction with tirzepatide is estimated at $985 (95% CI: $908-$1075) compared with $1845 (95% CI: $1707-$1989) with semaglutide.

This suggests that while the total costs may be similar, tirzepatide provides better value for money than semaglutide for weight reduction due to its greater efficacy at a lower cost per 1% of weight loss. However, it’s important to note that semaglutide (Wegovy) is FDA-approved for chronic weight management, while tirzepatide (Mounjaro) is only approved for type 2 diabetes, so its use for weight loss is off-label. Patients should discuss the potential risks, benefits, and costs with their healthcare provider to determine the best treatment option.

Tirzepatide vs Semaglutide Dosage For Weight Loss

Tirzepatide and semaglutide are both used for weight loss, but they have different dosing schedules and mechanisms of action.

Tirzepatide Dosing Schedule

• Tirzepatide is available in doses up to 15 mg and is administered once weekly.
• The highest dose of tirzepatide (15 mg) is more effective at reducing body weight and blood sugar levels compared to lower doses.

Semaglutide Dosing Schedule

• Semaglutide is available in doses up to 2.4 mg and is administered once weekly.
• To reach the maintenance dose level of 2.4 mg, you must take four escalation doses over four months.

Comparison Of Dosing Schedules

• Tirzepatide has a more straightforward dosing schedule, with a single weekly dose, whereas semaglutide requires a more complex escalation process to reach the maximum dose.
• Tirzepatide’s higher doses (10 mg and 15 mg) have been shown to be more effective for weight loss compared to semaglutide’s highest dose (2.4 mg)

Results

Across the SURMOUNT program, tirzepatide demonstrated superior weight loss efficacy compared to semaglutide at all dose levels studied.

In SURMOUNT-1 (N=1984), participants without diabetes receiving tirzepatide 5 mg, 10 mg, or 15 mg achieved 16%, 22.1%, and 24.2% mean weight reductions versus 6.2% and 8.6% with semaglutide 1 mg and 2.4 mg, respectively.

Among SURMOUNT-2 participants (N=937) with type 2 diabetes, tirzepatide resulted in 13.1%, 15.7%, and 19.5% weight reductions at 5 mg, 10 mg, and 15 mg doses versus 9.6% for semaglutide 1 mg.

Similarly in SURMOUNT-3 (N=504), weight reductions of 13.2%, 16.8%, and 20.9% occurred with ascending tirzepatide doses, compared to 6.7% with semaglutide 1 mg.

The proportion of participants achieving over 15% weight loss, a clinically meaningful threshold, was approximately doubled with tirzepatide 15 mg (51-63%) versus semaglutide 2.4 mg (28-35%). Superior reductions in waist circumference and improvements in cardiovascular risk markers like triglycerides further favored tirzepatide.

From a glycemic control perspective, changes in HbA1c and fasting plasma glucose levels demonstrated tirzepatide’s non-inferiority or superiority compared to semaglutide across trials in participants with type 2 diabetes.

The most common adverse events with both drugs included gastrointestinal symptoms like nausea, diarrhea, and constipation. Discontinuation rates due to adverse events were 7.1-11.3% with tirzepatide versus 3.1-7.9% with semaglutide. While rates of serious treatment-emergent adverse events were similar between groups, higher frequencies of cholelithiasis and pancreatic enzyme elevations occurred with tirzepatide.

Conclusion

The SURMOUNT trials provide compelling evidence that the dual GIP/GLP-1 receptor agonist tirzepatide promotes greater weight loss than the selective GLP-1 agonist semaglutide. At the highest tested doses, approximately twice as many participants achieved over 15% weight reduction with tirzepatide versus semaglutide after 72 weeks.

Tirzepatide’s incretin co-agonism may underlie this enhanced metabolic efficacy, though the two medications share a comparable overall safety profile. While gastrointestinal intolerability is common to both drugs, vigilance for treatmentemergent gallbladder disease and pancreatic effects is warranted with tirzepatide.

In summary, tirzepatide represents a promising anti-obesity medication that appears more efficacious than existing GLP-1 agonists like semaglutide. However, shared decision-making between clinicians and patients remains crucial when selecting among available weight loss pharmacotherapies, considering each regimen’s benefits, risks, and administration considerations. As with any chronic treatment, close monitoring for individual responses and adverse effects is essential.