Tirzepatide Outperforms Semaglutide for Weight Loss in Adults

A study published in JAMA Internal Medicine compared the effectiveness of semaglutide and tirzepatide in adults who are obese 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. 

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.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 participants discontinued the medications, and this number was slightly higher for participants taking tirzepatide. 

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, researchers 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. 

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 has semaglutide effects. 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. 

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