Semaglutide or Tirzepatide: Which is Better for You?

Are you stuck wondering which GLP-1 medication is better for you? Semaglutide or tirzepatide. Though your healthcare provider is your biggest advocate, let’s discuss some important considerations along the way. When managing type 2 diabetes or weight loss, choosing the right medication is crucial for optimal outcomes. Semaglutide and tirzepatide are two injectable therapies that have gained attention due to their effectiveness. Semaglutide is approved as Ozempic® for management of type 2 diabetes and Wegovy^® for weight management. Tirzepatide is approved as Mounjaro^® for management of type 2 diabetes and Zepbound^® for weight management. This article is a summary of a recent study¹ published comparing the efficacy and safety of tirzepatide vs semaglutide for adults of both sexes with type 2 diabetes mellitus. This study evaluated a total of 28 clinical trials with 23,622 participants to determine how semaglutide compared to tirzepatide for blood glucose and weight management. We will review the data, focusing on their effectiveness, safety, and practical considerations for you to consider.

Comparison of Tirzepatide to Semaglutide

The chart below compares the effects of tirzepatide and semaglutide on three key metrics: HbA1c reduction, body weight reduction, and discontinuation due to gastrointestinal adverse events (GI AEs). The negative values in the chart highlight the superiority of tirzepatide over semaglutide in both HbA1c and body weight reductions.

Effectiveness in Blood Glucose Control

Both semaglutide and tirzepatide have shown effectiveness in managing blood glucose levels in adults with type 2 diabetes. Below are the results from this specific study:

Semaglutide:

• Administered in doses of 0.5 mg, 1.0 mg, and 2.0 mg once weekly, semaglutide has been effective in reducing HbA1c levels. The higher dose of 2.0 mg showed a reduction of 17.74 mmol/mol (1.59%) from baseline.

Tirzepatide:

• Available in doses of 5 mg, 10 mg, and 15 mg once weekly. The highest dose of 15 mg resulted in the most substantial HbA1c reduction of 21.61 mmol/mol (1.96%). Notably, tirzepatide at all doses was comparable or superior to semaglutide in lowering HbA1c levels.

Effectiveness in Weight Loss

Both semaglutide and tirzepatide have shown significant efficacy in managing weight loss in adults. Let’s identify what the study found below:

Semaglutide:

• Weight reductions with semaglutide ranged from 2.52 kg to 4.97 kg (5.54 lbs to 10.93 lbs), depending on the dose.

Tirzepatide:

• Demonstrated greater weight loss, with reductions ranging from 5.27 kg to 9.57 kg (11.59 lbs to 21.05 lbs). The highest dose of 15 mg was particularly effective.

Safety and Adverse Effects

Both medications are associated with gastrointestinal side effects, which are the most common adverse events. Let’s see how the safety and adverse effects compared below:

Semaglutide:

• Side effects include nausea, vomiting, and diarrhea, with increased incidence at higher doses.
• No significant increase in serious adverse events or severe low blood glucose was observed.

Tirzepatide:

• Similar to semaglutide, tirzepatide also caused gastrointestinal issues, with the severity increasing with the 15 mg dose.
• Like semaglutide, it did not significantly increase the risk of severe adverse events or low blood glucose.

Directions for Use: Semaglutide or Tirzepatide

In evaluating the appropriate therapy, as a pharmacist I recommend considering several factors:

Blood Glucose Targets:

• For those needing substantial HbA1c reduction, tirzepatide might be preferred due to its higher efficacy at maximum doses.

Weight Management Goals:

• If weight loss is a critical component of the treatment plan, tirzepatide again shows greater potential benefits.

Cardiovascular Benefits:

• Semaglutide stands out as it significantly reduces major adverse cardiovascular events (MACE) by 26% in patients with type 2 diabetes (SUSTAIN-6)² and is the only weight loss medication approved to lower the risk of major cardiovascular events, such as death, heart attack, or stroke, in adults with known heart disease and obesity or overweight (SELECT)³. Meanwhile, tirzepatide has not increased the risk of MACE in type 2 diabetes patients (SURPASS-4)⁴ and has been shown to lower the 10-year predicted risk of atherosclerotic cardiovascular disease (ASCVD) in overweight and obese adults⁵. Currently, the cardiovascular benefits of tirzepatide are being investigated in large, international phase 3 studies, including those focusing on individuals with obesity or overweight without diabetes (SURMOUNT-MMO; NCT05556512) and those with type 2 diabetes (SURPASS-CVOT; NCT04255433).

Kidney Protective Benefits:

• The FLOW Trial⁶ showed semaglutide provides significant kidney protective benefits, reducing the risk of major kidney disease events and cardiovascular outcomes in patients with type 2 diabetes and chronic kidney disease. On the other hand, while tirzepatide shows promising results in glycemic control and weight loss, its specific kidney protective benefits are still under investigation, with preliminary data suggesting potential renal benefits that require further validation. In summary, semaglutide currently offers more established kidney protective benefits, making it a stronger option for patients with type 2 diabetes or kidney health concerns. However, ongoing research may further elucidate tirzepatide’s renal effects.

Tolerance and Side Effects:

• Both medications can cause gastrointestinal discomfort, but your tolerance to these side effects should guide the choice.
• Monitoring and managing these side effects is crucial for adherence and overall treatment success.

Dosing Convenience:

• Both medications are administered weekly, offering convenience over daily medications. Preference and lifestyle should be considered in the final decision.

Drug Availability and Cost

• Both medications have faced periodic shortages, which can affect treatment continuity.
• Insurance approvals have been very challenging, on top of the drug shortages.
• High cost and long-term commitment required for these therapies should be carefully considered in the decision-making process, balancing clinical benefits with financial impact.

Conclusion

Both semaglutide and tirzepatide are effective therapies for type 2 diabetes and weight management, with tirzepatide showing a slight edge in efficacy for both glycemic control and weight loss. This enhanced effectiveness may be attributed to its additional mechanism of action on the GIP hormone, which plays a significant role in glucose regulation and appetite suppression. These findings are consistent with the results from the SURPASS-2 trial⁷, which demonstrated similar benefits of tirzepatide over semaglutide. However, semaglutide offers superior cardiovascular and renal protective benefits, making it an excellent choice for patients who are at high risk for these complications, especially those with type 2 diabetes and chronic kidney disease.

When determining the right therapy, it is essential to consider not only diabetes and weight management efficacy but also cardiovascular and renal protective benefits. The choice between these medications should be personalized to your specific health goals, side effects, overall treatment plan, cost, and availability of the medication. It’s important to also note that both medications require long-term commitment. Regular follow-ups and consultations with healthcare providers are crucial to optimize therapy and achieve the best outcomes.

As a pharmacist, I believe it’s crucial to weigh the clinical data alongside practical aspects such as drug availability and cost. Periodic shortages and the high cost of these therapies highlight the importance of education and ongoing support, ensuring that individuals are well-informed about their options and can maintain adherence in the long-term. This personalized approach aligns well with the ethos of providing comprehensive health insights, as we do through the Well-Rounded Pharmacist platform.

References

1. Karagiannis T, Malandris K, Avgerinos I, et al. Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials. Diabetologia. 2024 Jul;67(7):1206-1222. doi: 10.1007/s00125-024-06144-1. Epub 2024 Apr 13. PMID: 38613667; PMCID: PMC11153294. ↩︎
2. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsbøll T; SUSTAIN-6 Investigators. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016 Nov 10;375(19):1834-1844. doi: 10.1056/NEJMoa1607141. Epub 2016 Sep 15. PMID: 27633186. ↩︎
3. Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, Hardt-Lindberg S, Hovingh GK, Kahn SE, Kushner RF, Lingvay I, Oral TK, Michelsen MM, Plutzky J, Tornøe CW, Ryan DH; SELECT Trial Investigators. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023 Dec 14;389(24):2221-2232. doi: 10.1056/NEJMoa2307563. Epub 2023 Nov 11. PMID: 37952131. ↩︎
4. Del Prato S, Kahn SE, Pavo I, Weerakkody GJ, Yang Z, Doupis J, et al. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet. 2021;398:1811–1824.  ↩︎
5. Hankosky ER, Wang H, Neff LM, et al. Tirzepatide reduces the predicted risk of atherosclerotic cardiovascular disease and improves cardiometabolic risk factors in adults with obesity or overweight: SURMOUNT-1 post hoc analysis. Diabetes Obes Metab. 2024; 26(1): 319-328. doi:10.1111/dom.15318  ↩︎
6. Perkovic V, Tuttle KR, Rossing P, et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024;391(2):109-121. doi:10.1056/NEJMoa2403347 ↩︎
7. Frías JP, Davies MJ, Rosenstock J, et al. SURPASS-2 Investigators. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021 Aug 5;385(6):503-515. doi: 10.1056/NEJMoa2107519. Epub 2021 Jun 25. PMID: 34170647. ↩︎

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