Semaglutide vs Tirzepatide (Clinical trial)

GLP1 Receptor agonists are amazing – the most popular formulations (Semaglutide and Tirzepatide) have taken the world by storm (Ozempic/Wegovy and Mounjaro/Zepbound). They're changing peoples' lives and making it much easier to manage type 2 diabetes and obesity.

Up until now, we've mostly been able to only compare the results of various trials (funded by formulation manufacturers like Novo Nordisk and Eli Lilly) to figure out which might be more effective, and a summary has crystalized:

• Semaglutide is a single agonist (GLP1 receptors)
• Tirzepatide is a dual agonist (GIP & GLP1 receptors)
• Tirzepatide outperforms GLP1 for weight loss

These insights though, you have to patch together via analysis – looking at papers and comparing sample sizes/efficacy and the outcomes of trials.

One of the things we almost never get is a direct comparison between the two, in a clinical setting, on the same participants.

Finally, there's a trial that compares Semaglutide and Tirzepatide "head to head":

Tirzepatide as Compared with Semaglutide for the Treatment of Obesity - PubMed

Among participants with obesity but without diabetes, treatment with tirzepatide was superior to treatment with semaglutide with respect to reduction in body weight and waist circumference at week 72. (Funded by Eli Lilly; SURMOUNT-5 ClinicalTrials.gov number, NCT05822830.).

PubMedLouis J Aronne

What did the trial find?

Simply, the study confirmed what most already thought/analyzed/saw in anecdata: Tirzepatide (Mounjaro/Zepbound) is more effective than Ozempic.

Both medications are highly effective, but Tirzepatide just does more when it comes to losing weight.

So let's get to the facts, for those who didn't click through and read the article above:

• 751 people participated in the study
  • These people were obese but DID NOT suffer from type 2 diabetes
• Participants received the maximum tolerated dose of Tirzepatide/Semaglutide
  • 10/15mg for Tirzepatide
  • 1.7/2.4mg of Semaglutide
• At 72 weeks (~1yr 5months) Tirzepatide users lost 20.2% body weight on average
  • Waist circumference decreased by 18.4cm
• At 72 weeks, Semaglutide users lost 13.7% body weight on average
  • Waist circumference decreased by 13.0cm
• The Tirzepatide group were more likely to lose weight across a variety of outcomes (10%, 15%, 20%, 25% of body weight)
• The negative side effects in both groups were mild to moderate, and mostly gastrointestinal (this is inline with what we know already about negative side effects)

This ends some arguments, and starts others.

The study was small, but it is a huge piece of evidence in the discussion on which is better. Being able to scientifically measure these formulations head to head says a lot about the safety and efficacy of either, and more importantly in relation to each other.

What works for each individual person can be different. The most dangerous side effects to look out for are still gastro-intestinal, and the most dangerous effects can come from just succeeding in losing weight:

Pancreatitis and Gallstones after massive weight loss

We look into pancreatitis and gallstones issues that caused one death and more hospitalizations, caused at least in part by GLP1s

GLP1 GuideGLP1.Guide Staff

What's best for any given person is still something that should be decided with medical professionals and a caring, informed physician.

Both are still better than Liraglutide

Unfortunately, the only generic-available GLP1 these days is Liraglutide, and it performs worse than Semaglutide (though both are effective):

Semaglutide & Liraglutide continue to be effective

Semaglutide and Liraglutide continue to be researched and studied and produce positive results for weight loss and medical outcomes.

GLP1 GuideGLP1.Guide Staff

Having an option in the market that is available as a generic is still a win though.