The news around the world has been red-hot this week with the publication of the first phase 3 trial of tirzepatide for weight management in the New England Journal of Medicine. 

In follow up to my blog on the high level results back in April,  let’s now dig further into the details!


This global study enrolled 2,539 participants with overweight or obesity, without diabetes, and randomized them to receive tirzepatide 5mg, 10mg, 15mg, or placebo.


At baseline, the average body weight was 105kg (231lb), with mean BMI of 38.   About 40% had prediabetes at baseline. Representation across various ethnicities was better than most obesity trials (which have for far too long been predominantly Caucasian). Two thirds of participants were female, and average age was 45.


At 72 weeks, they found an average weight loss of:

  • 15% with tirzepatide 5mg
  • 19.5% with tirzepatide 10mg
  • 20.9% with tirzepatide 15mg (almost 50lb)
  • 3.1% with placebo



  • 30% of people achieved at least 20% weight loss with tirzepatide 5mg
  • 50% of people achieved at least 20% weight loss with tirzepatide 10mg
  • 57% of people achieved at least 20% weight loss with tirzepatide 15mg
  • 3.1% of people achieved at least 20% weight loss with placebo


Over 95% of people with prediabetes at baseline converted to normal blood sugars by the end of the trial with tirzepatide, which is not unexpected, given that tirzepatide is also a diabetes medication (approved for the treatment of type 2 diabetes in USA in April 2022). It is notable that 62% of those in placebo also converted to normal blood sugars, speaking to the power of lifestyle changes to revert prediabetes to normal sugars (though difficult to sustain over the long term).


Systolic blood pressure decreased by -7.2mmHg in the pooled tirzepatide group, vs -1mmgHg in placebo, which is similar to the effect of a blood pressure medication.


As blogged previously, the most common side effects were gastrointestinal in nature (most commonly nausea, diarrhea, constipation), mostly transient, mild to moderate in severity, and in keeping with what we know of the GLP1 class of medication.  There were 4 cases of pancreatitis in the study, with one in each treatment group (including placebo).  Gallstones were similar across treatment groups (7, 9, 4, and 6 cases in the tirzepatide 5mg, 10mg, 15mg, and placebo groups, respectively).  Gallbladder inflammation (cholecystitis) was more frequent in the tirzepatide groups, but rates were low (≤0.6%).


It is interesting that weight was still going down a little in the 10mg and 15mg tirzepatide groups at the end of the 72 week study.  In studies of other weight management medications, weight has usually plateaued by a year on treatment.  There is an additional 2 year treatment period underway for people with prediabetes in this study, which will inform us on maximum and long term weight lowering effect of tirzepatide, as well as its capacity to prevent type 2 diabetes.


As a clinician, one wonders whether tirzepatide could cause too much weight loss for some folks.  Only 5.5% of participants in this study had a starting BMI of 27-30 (by BMI, this is the ‘overweight’ category); further evaluation and study is needed in this group.  If approved for weight management, a clinician could consider simply using a lower dose of medication for those who need less weight loss, and a higher dose for those who need more.


BOTTOM LINE: This is the first time that a large clinical trial of a potential weight loss medication shows an average weight loss of over 20%, approaching the amount of weight loss success that we see with bariatric surgery.   Another step forward in the obesity field!


Disclaimer: I was an investigator in the tirzepatide clinical trial program for type 2 diabetes.  I receive honoraria as a continuing medical education speaker and consultant from the makers of tirzepatide (Eli Lilly). 


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