Semaglutide or tirzepatide, which is better?

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Researchers have compared the effectiveness of weight loss medications such as tirzepatide and semaglutide. Jaap Arriens/NurPhoto via Getty Images
  • Tirzepatide and semaglutide are both type 2 diabetes medications that can also assist people with weight loss.
  • Results from a recent study suggest that tirzepatide may be more effective in helping people who have obesity or overweight lose weight than semaglutide.
  • People interested in using medications for weight loss can speak with their doctors to see if they are appropriate candidates for weight loss medications.

Maintaining a healthy weight can be challenging, but it is essential to a healthy lifestyle. Certain medications can be helpful for some people who are trying to lose weight. However, weight loss medications can vary in effectiveness, and researchers are interested in finding the best choices.

A study published in JAMA Internal Medicine compared the effectiveness of semaglutide and tirzepatide in adults who have obesity or overweight.

The researchers found that while both groups lost weight, tirzepatide was more effective than semaglutide when it came to weight loss.

This piece of research adds essential data to what experts understand about these weight loss medications and may contribute to clinical guidelines in the future.

Semaglutide and tirzepatide are both medications that assist with chronic weight management. The Food and Drug Administration (FDA) has approved versions of these medications for certain eligible individuals.

However, research on these medications is ongoing, including how they compare. Researchers of the current study wanted to compare the effectiveness of semaglutide and tirzepatide labeled for type 2 diabetes. They wanted to see which injectable medication resulted in more weight loss.

This research was a propensity-matched cohort study that included individuals with obesity or overweight who were new users of tirzepatide or semaglutide.

The researchers collected information via electronic health records and linked third-party data. They looked at the changes in body weight that participants experienced at three months, six months, and one year.

In all, researchers included 18,386 participants in the propensity score-matched cohort. Of this number, 52% percent of the group had type 2 diabetes, and the average age of participants was 52. The average follow-up time with participants was 165 days, and slightly over 50% of participants discontinued each medication. The researchers took note of gastrointestinal adverse events that occurred among participants and found that the risk was similar for both medication groups.

Overall, the study found that tirzepatide was more effective at helping participants lose weight. About 82% of participants taking tirzepatide experienced 5% or greater weight loss. In comparison, only 66.5% of participants taking semaglutide achieved this level of weight loss.

Study author Patricia Rodriguez, PhD, MPH, principal applied scientist at Truveta, which partly funded the study, noted the following additional highlights of the study’s findings, to MNT:

“Patients on tirzepatide were over two times more likely to experience 10% weight loss and three times more likely to experience 15% weight loss within a year, compared to patients on semaglutide. Our study also found that, in general, patients without type 2 diabetes experienced greater weight loss than patients with type 2 diabetes, but tirzepatide was more effective than semaglutide in both groups.”

Study author Nick Stucky, MD, PhD, vice president of Truveta Research and practicing infectious disease physician with Providence Portland Medical Center, noted the following about the study to Medical News Today:

“While tirzepatide was significantly more effective than semaglutide, patients on both medications experienced substantial weight loss and we observed no difference in the risk of GI adverse events.”

“In addition to effectiveness, factors like medication availability and insurance coverage will likely play a role in deciding which medication to initiate. So, providers should evaluate these findings – alongside those other considerations – as they assess which option might be best for their individual patients,” he said.

This research does have limitations. For example, about 77% of the propensity-matched cohort were white, and 70% were female, meaning that future studies could include more diversity among participants. The geographical distribution of the sample did not represent the United States population, so the results cannot be generalized.

The study is also limited because of its use of clinical electronic health record data, which could have resulted in delayed times and under-reported adverse events.

The researchers limited their analysis to participants who regularly interacted with the health care system the year before getting their injectable weight loss medication. The authors acknowledge that drug shortages during the study could have resulted in some substitutions, which could have impacted the results.

There is also some risk for unmeasured confounding, and factors like bias because of unmeasured variables, dosing differences, using brand as a proxy for target dose, and missing information could have affected the results.

The researchers note that since weight loss is observable to participants, this could have led to informative censoring and participant action to discontinue or switch medications. The study also only focused on medicines labeled for type two diabetes, so future research can look at medications specifically labeled for weight loss.

There was also a difference in weight loss between participants with type 2 diabetes and those without, so more research can look at differences between these groups such as engagement in other weight loss activities and other underlying reasons.

Finally, over half of the of participants discontinued the medications, and this number was slightly higher for participants taking tirzepatide.

Rodriguez noted the following areas of continued research to Medical News Today:

“There is still so much to learn about this class of medication, including how it can help to treat other conditions, long-term clinical outcomes, barriers to equitable access, the effects of discontinuation, trends in reinitiation, which dose of each drug might be most effective (pharmacodynamics), and more.”

“In fact, we continue to explore the trends in prescriptions and dispense in our quarterly GLP-1 monitoring report, which looks at these trends over time and might provide some insight into access and availability,” she continued.

Rodriguez said the latest summary will be available on their company blog “[within] the next month or so”, followed by the full analysis being published on pre-print server MedRxviv.

In addition, there are also challenges related to the differences between semaglutide and trizepatide. Mir Ali, MD, board-certified bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, who was not involved in the study, shared his thoughts with MNT:

“This study confirms what I have seen in other studies comparing the two medications. Clinically, if possible, then tirzepatide would be the preferred medication for weight loss. It works on two receptors as opposed to one that semaglutide affects. However, getting these medications covered by insurance is a challenge and appears worse for tirzepatide. Additionally, tirzepatide is more expensive.”

Having obesity or overweight can increase the risk for other health conditions like type 2 diabetes, high blood pressure, and even some cancers.

Weight management and weight loss can involve several strategies, such as physical activity and diet changes. Individuals can gain insight by seeking guidance from a number of health professionals.

Individuals who are interested in using weight loss medications like semaglutide and trizepatide can ask their doctors about the appropriateness of these treatments for them.

“The first steps in trying to get these medications for weight loss is for a person to see their primary care doctor. Their doctor can determine which medication is appropriate for them, what are the risks versus benefits, and if they meet insurance criteria. They may also contact their insurance company directly to ascertain coverage and benefits,” Ali said.

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