In choosing the best GLP1-based medication for our patients with type 2 diabetes at high risk of cardiovascular disease, guidelines recommend choosing one that has proven reduction in risk of CV events in cardiovascular outcome trials (CVOTs). The three marketed GLP1 receptor agonists that have previously met this bar are dulaglutide (Trulicity), liraglutide (Victoza), and semaglutide (Ozempic as an injection, and Rybelsus as a pill).

Based on top line results just released for the SURPASS-CVOT study, we can now add tirzepatide (Mounjaro) to that list. As tirzepatide is the first and only dual GIP/GLP1 receptor agonist currently available, it is especially important to have cardiovascular outcome trial data on this medication.

The SURPASS-CVOT trial was a study of 13,299 people with type 2 diabetes and cardiovascular disease, with a unique set up – rather than comparing tirzepatide to placebo as is typical of CVOTs, participants were randomized to receive either tirzepatide at maximum tolerated dose (5mg, 10mg, or 15mg weekly), or dulaglutide. As per the baseline characteristics paper, the average age of participants was 64, diabetes duration 14.7 years, baseline A1c (diabetes report card) 8.4%, and BMI 32.6.

The high level results report that the reduction in risk of cardiovascular events (heart attack, stroke, or cardiovascular death) was similar for tirzepatide vs dulaglutide (clinicians/scientists: HR 0.92, CI 0.83-1.01). Since we know that dulaglutide reduces cardiovascular events from the 2019 REWIND trial (blogged here; disclosure, I was an investigator), we can now say the same for tirzepatide. The high level results also report that the rate of death from any cause was reduced by 16% with tirzepatide vs dulaglutide (HR 0.84, CI 0.75-0.94).

In addition, the SURPASS-CVOT team looked at a comparison of the tirzepatide group in SURPASS-CVOT and compared them to the placebo group in the REWIND trial, to give an estimate of what benefit tirzepatide might have compared to placebo. While we have to take this analysis with a big grain of salt as we are looking at two separate trials here, this analysis found a 28% reduced risk of CV events with tirzepatide and 39% reduction in risk of death from any cause, compared to a putative placebo.

The high level SURPASS-CVOT results also report kidney protection with tirzepatide, slowing kidney function decline by 3.54 mL/min/1.73m2 at 3 years vs dulaglutide. As expected, the tirzepatide group also had greater improvements in diabetes control (A1c -1.73% vs -0.9% with dulaglutide), weight loss (-12.1% vs -5.0% with dulaglutide), blood pressure, and other metabolic health parameters. During the trial, 13.3% of people taking Mounjaro stopped treatment due to adverse events, vs 10.2% of people in the Trulicity group.

So what does this mean for people with type 2 diabetes? While we need the full results published before we can draw firm conclusions (expected in September), these high level results suggest that Mounjaro reduces cardiovascular risk in people with type 2 diabetes and cardiovascular disease. It did not fare better than Trulicity, which is a ‘weaker’ GLP1 medication from a blood sugar and weight loss perspective. To me, this supports that there are likely other mechanisms for CV benefit at play with GLP1-based medications, such as reduction in inflammation (other data from other studies of GLP1 medication support this as well).

Tirzepatide is also being studied to see if it can reduce cardiovascular events in people with obesity, without diabetes, in the SURMOUNT-MMO trial (disclosure: I am an investigator in this study). An interesting aspect of this study is that some people enrolled in this study have cardiovascular disease, and some do not (but are at high risk). This study is estimated to report near the end of 2027.

BOTTOM LINE: Based on topline results from the SURPASS-CVOT trial, tirzepatide (Mounjaro) reduces cardiovascular risk in people with type 2 diabetes and cardiovascular disease. I look very forward to digging into the full results in the expected publication in September!

Disclaimer:  I am/have been an investigator in clinical trials of tirzepatide, dulaglutide, liraglutide and semaglutide. I was involved as an investigator in the REWIND trial. I receive honoraria as a continuing medical education speaker and consultant from the makers of tirzepatide and dulaglutide (Eli Lilly), and semaglutide and liraglutide (Novo Nordisk).

Share this blog post using your favorite social media link below!

Follow me on X/twitter! @drsuepedersen

Check me out on Insta! drsuepedersen

www.drsue.ca © 2025