Tirzepatide vs. Semaglutide vs. Cagrilintide vs. Retatrutide vs. Mazdutide for Weight Loss: Which Works Best?

Tirzepatide vs. Semaglutide Weight Loss & Side Effects

For starters, let’s compare tirzepatide vs. semaglutide, the two most popular weight loss peptides. We found two similar, large-scale studies, one with a 2.4 mg dose of semaglutide versus placebo for 68 weeks, and another with 5, 10, and 15 mg doses of tirzepatide vs. placebo for 72 weeks. 

Each person took one injection of either peptide a week. Here are the findings:

As we can see, Tirzepatide was significantly more effective than semaglutide, producing greater weight loss and having more people with 5% or greater weight loss. 

Interestingly, higher tirzepatide (10 and 15 mg) doses seemed to cause more people to quit the study due to side effects than semaglutide. 

This is contrary to what we hear from individual reports of people from reddit and other online forums. In most of these anecdotal reports, people claim that semaglutide has worse side effects than tirzepatide, which is one of the main reasons they switched over. 

Cagrilintide vs. Retatrutide vs. Mazdutide Weight Loss & Side Effects

So we can say pretty concivisibly that tirzepatide is superior to semaglutide. But what about newer weight loss peptides that are just hitting the market, like cagrilintide, retatrutide, and mazdutide? 

Comparing these is a little more difficult because there is less research data, but we can get a pretty good comparison. As expected, the higher doses produced higher weight loss in each study. 

As we can see:

1. Retatrutide showed the overall best results, leading to average 7.2-17.5% dose-dependant weight loss by 24 weeks and 8.7-24.2% by 48 weeks
2. Mazdutide came in second with 6.7-11.3% dose-dependant weight loss by 24 weeks
3. Cagriintide had 6-10.8% dose-dependant weight loss by 26 weeks (fairly close to 24 weeks)

All together, retatrutide produced the greatest weight loss after 24 weeks, even after accounting for the fact that people in the Mazdutide study started at a lower overall BMI. 

Side Effects

But what about safety and side effects? Just like their older brethren, all three of these newer weight loss peptides produced gastrointestinal side effects in most study participants. 

Keep in mind it’s more difficult to compare safety; for example, some people might quit the study based on side effects but not report it correctly. Still, here are the findings:

1. With mazdutide, only 1 person said they quit the study because of side effects, out of a total 19 people who quit the study early.
2. In the cagrilintide study, 4% withdrew from the study due to side effects.
3. For the retatrutide study, 6-16% of people withdrew from the study because they didn’t like the side effects, with the higher percentage for people taking higher doses. 

In summary, it looks like mazutide is the safest of the three new generation weight loss peptides, as only one person clearly quit the study because of side effects. That’s not surprising because it’s the newest peptide out of the three, and researchers tend to improve the safety profile with each new peptide.

Even if we account for some people quitting the mazdutide study without clearly stating it was because of side effects, it’s still the safest of the three. Cagrilintide comes in second place with 4% discontinuing due to side effects.

In summary, it looks like out of mazdutide, retatrutide, and cargrilintide, retatrutide is the best for weight loss but also produced the most side effects, whereas maztutide is the safest but led to less weight loss. 

Tirzepatide vs. Semaglutide vs. Cagrilintide vs. Retatrutide vs. Mazdutide Weight Loss

Now, let’s compare all five peptides together. Again, a direct 1:1 comparison is not possible because the studies were done for different lengths of time, slightly different designs, and reported their data in slightly different ways.

Still, we can get a general picture by comparing the estimated 24/26 week findings for tirzepatide and semaglutide (taken from the study graphs) to the 24-26 week findings for cagrilintide, retatrutide, and mazdutide. 

*Estimated weight loss based on graphs provided in the studies

As we can see:

1. High-dose retatrutide (12 mg) is the winner, producing the most weight loss after 24 weeks.
2. High-dose tirzepatide (24 weeks) takes second place.
3. Mazdutide takes third place, but is the safest in terms of side effects.
4. Semaglutide (26 weeks) barely beats out cagrilintide.

Overall, the results are a bit surprising. We expected the three newer-generation peptides to beat out the older ones in weight loss, but tirzepatide got 2nd place and semaglutide beat out cagrilintide.

Data Limitations

It’s important to note that while this data is useful for a general picture, it’s not perfect:

1. Some studies lasted longer than others or recorded weight loss data at different time points. As a result, a 1:1 comparison isn’t always possible and we had to estimate some data points from graphs.
2. The data on people withdrawing a study is not always 100% clear. For example, even though the mazdutide study only reported one person quitting due to side effects out of 19 people who didn’t finish the trial, it’s possible there were more.
3. The tirzepatide & semaglutide studies had more participants, so their data is stronger and more reliable than that of the newer peptides.
4. The participants in the Mazdutide study had a BMI of 24+ (overweight) or 28+ (obese), which is lower than the 27+ and 30+ cutoff used in the other studies. That means their results are arguably a bit better than the numbers suggest.