Tirzepatide vs. Semaglutide: Which Weight Loss Medication is Better?
Obesity has reached epidemic proportions globally, posing a significant threat to public health. The World Health Organization estimates that worldwide obesity has nearly tripled since 1975.
The American Medical Association recognizes obesity as a chronic disease requiring comprehensive medical care, including lifestyle interventions and pharmacotherapy.
Among the newer medications for chronic weight management, tirzepatide and semaglutide have garnered considerable attention for their efficacy in promoting weight loss.
Both are glucagon-like peptide-1 (GLP-1) receptor agonists, a class of drugs that mimic the effects of incretin hormones naturally produced in the gut.
These hormones play a crucial role in regulating appetite, blood sugar levels, and digestion. While semaglutide acts primarily on GLP-1 receptors, tirzepatide is unique in its dual-action mechanism, targeting both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors.
This dual-receptor activation may contribute to tirzepatide’s superior weight loss outcomes observed in clinical trials. This article provides a detailed comparative analysis of tirzepatide and semaglutide, examining their mechanisms of action, efficacy, safety profiles, and other factors relevant to clinical decision-making.
Mechanism of Action
Semaglutide and tirzepatide belong to the GLP-1 receptor agonist class of medications. GLP-1 is an incretin hormone that stimulates insulin secretion, suppresses glucagon release, and slows gastric emptying, leading to improved blood sugar control and weight loss.
Semaglutide primarily targets the GLP-1 receptor. By activating this receptor, semaglutide stimulates insulin secretion, suppresses glucagon release, slows gastric emptying, and promotes a sense of fullness, leading to better blood sugar control and weight loss.
Tirzepatide targets two receptors, including the GLP-1 and GIP. This dual-receptor approach helps regulate blood sugar, increase insulin secretion, reduce glucagon production, and slow gastric emptying, resulting in improved glycemic control and weight loss.
Both GIP and GLP-1 receptors are found in areas of the brain important for appetite regulation. Tirzepatide decreases calorie intake, and the effects are likely mediated by affecting appetite.
Effectiveness for Weight Loss
Both medications have shown promising results in weight loss. Clinical trials indicate that tirzepatide may be superior to semaglutide in this regard, likely due to its dual-receptor action.
Across multiple studies, tirzepatide consistently shows superior weight loss results compared to semaglutide. In a 72-week head-to-head trial known as SURMOUNT-5, participants using Zepbound (tirzepatide) lost 50.3 lbs (22.8 kg) on average, while participants on Wegovy (semaglutide) lost 33.1 lbs (15.0 kg).
This translates to an average weight loss of 20.2% with tirzepatide compared to 13.7% with semaglutide. Notably, tirzepatide provided a 47% greater relative weight loss compared to semaglutide in this trial.
In another study, individuals with overweight or obesity treated with tirzepatide were significantly more likely to achieve clinically meaningful weight loss and larger reductions in body weight compared with semaglutide.
Patients receiving tirzepatide were significantly more likely to achieve weight loss (≥5%; hazard ratio, 1.76; 95% CI, 1.68-1.84; ≥10%; HR, 2.54; 95% CI, 2.37-2.73; and ≥15%; HR, 3.24; 95% CI, 2.91-3.61).
On-treatment changes in weight were larger for patients receiving tirzepatide at 3 months (difference, -2.4%; 95% CI -2.5% to -2.2%), 6 months (difference, -4.3%; 95% CI, -4.7% to -4.0%), and 12 months (difference, -6.9%; 95% CI, -7.9% to -5.8%).
The speed and extent of weight loss with semaglutide can be influenced by individual factors such as metabolism, adherence to treatment, and lifestyle.
Side Effects
Both medications share a similar side effect profile, primarily related to the gastrointestinal system.
Common Side Effects:
- Nausea
- Vomiting
- Diarrhea
- Constipation
- Abdominal pain
These side effects are usually mild to moderate and often subside as the body adjusts to the medication. Tirzepatide may cause slightly more gastrointestinal distress at higher doses, especially during the initial weeks of treatment.
The incidence of gastrointestinal adverse events with Ozempic is higher during dose escalation, highlighting the importance of careful dose titration8. With semaglutide, higher doses and taking the medication on an empty stomach may increase nausea9.
Serious Side Effects:
In addition to the common side effects, both tirzepatide and semaglutide carry the risk of more serious adverse events.
Tirzepatide:
- Severe allergic reactions
- Thyroid tumors
- Pancreatitis
- Gallbladder problems
- Low blood sugar (hypoglycemia)
- Kidney damage
- Severe stomach problems
- Vision changes
- Suicidal thoughts and actions
Semaglutide:
- Inflammation of the pancreas (pancreatitis)
- Changes in vision
- Low blood sugar (hypoglycemia)
- Dehydration leads to kidney problems
- Severe stomach problems
- Serious allergic reactions
- Gallbladder problems
Other Potential Concerns:
- Diabetic Retinopathy: Mounjaro may worsen diabetic retinopathy. Patients with this condition should be closely monitored.
- Psychiatric Adverse Events: Both medications have been associated with psychiatric adverse events, such as depression, anxiety, and suicidal ideation. Patients should be screened for pre-existing psychiatric conditions and monitored for these symptoms.
Cost and Availability
The cost of tirzepatide and semaglutide can be a significant factor in treatment decisions. Both medications are relatively expensive, and insurance coverage varies.
Tirzepatide
The list price of tirzepatide without insurance or discounts ranges from $1,059.87 to $1,069.02 per month. A manufacturer’s savings card may be available for commercially insured patients, potentially reducing the cost to as low as $25 per month. The potential annual cost of tirzepatide can exceed $12,000.
Semaglutide
The average monthly cost of semaglutide without insurance is about $831. The list price of semaglutide without insurance or discounts is about $1,418 per month. Copay cards may be available, potentially reducing the cost to as low as $25 per month.
While cost and availability are important considerations, several other factors can influence the choice between tirzepatide and semaglutide.
Other Factors to Consider
- Individual health conditions: Certain medical conditions, such as a history of pancreatitis, gallbladder disease, or thyroid cancer, may preclude the use of one or both medications.
- Treatment goals: If weight loss is the primary goal, tirzepatide may be the preferred option due to its superior efficacy. However, if a patient has cardiovascular disease, semaglutide may be a better choice due to its proven cardiovascular benefits. Some physicians prefer tirzepatide over semaglutide due to its superior efficacy in weight loss and A1c reduction, but acknowledge the potential for increased side effects. Factors like insurance coverage, drug availability, and side effects also influence physicians’ choices, with some patients benefiting from the broader dosing options that tirzepatide offers.
- Patient preferences: Some patients may prefer semaglutide due to its longer track record and greater availability, while others may prefer tirzepatide due to its potentially greater weight loss benefits.
- Switching Medications: If one medication is not tolerated well, switching to the other is possible under the guidance of a medical professional. This may involve adjusting the starting dose.
Conclusion
Tirzepatide and semaglutide are both effective medications for weight loss. Across various studies and dosages, tirzepatide consistently demonstrates superior weight loss compared to semaglutide. Semaglutide has a longer track record and may offer cardiovascular benefits. The choice between these medications should be individualized based on patient-specific factors, including health conditions, treatment goals, and preferences.
This comparative analysis reveals that both tirzepatide and semaglutide are valuable tools in the management of obesity. While they share a similar mechanism of action as GLP-1 receptor agonists, tirzepatide’s dual-receptor activation translates to greater weight loss in clinical trials.
However, semaglutide boasts a longer history of use and has demonstrated cardiovascular benefits, which may be a crucial factor for some patients. Ultimately, the optimal choice hinges on a comprehensive assessment of individual needs, considering factors such as overall health, treatment goals, potential side effects, cost, and availability.
Shared decision-making between patients and healthcare providers is essential to ensure the chosen medication aligns with individual circumstances and preferences.
It is important to acknowledge the limitations of the available research. Some studies have a relatively short duration, and observational studies may have the potential for bias. Further research is needed to fully understand the long-term effects and comparative effectiveness of these medications.
| Medication | Mechanism of Action | Average Weight Loss | Common Side Effects | Serious Side Effects | Cost (without insurance) |
| Tirzepatide (Zepbound, Mounjaro) | Dual GIP and GLP-1 receptor agonist | 20.20% | Nausea, vomiting, diarrhoea, constipation, abdominal pain | Thyroid tumours, pancreatitis, gallbladder problems, kidney damage | $1,059.87 – $1,069.02 per month |
| Semaglutide (Wegovy, Ozempic) | GLP-1 receptor agonist | 13.70% | Nausea, vomiting, diarrhoea, constipation, abdominal pain | Pancreatitis, gallbladder problems, kidney problems | $1,418 per month |