Stephen Nicholls, PhD, MBBS, Monash University and Victorian Heart Hospital, explains how he works closely with patients and study sites in SURPASS-CVOT to avoid weight loss drug discontinuation and weight regain.
Some of the discussion around GLP-1–based weight-loss therapies has been the practicality of taking them for many years, including the possibility of weight returning if patients stop taking the drug. Additionally, the inclusion criteria for SURPASS-CVOT has a body mass index (BMI) floor of 25 kg/m2 while SURMOUNT-1 and SURMOUNT-2 had a BMI floor of 27 kg/m2. Here, Stephen Nicholls, PhD, MBBS, Monash University and Victorian Heart Hospital, explains whether the 54-month duration of SURPASS-CVOT will offer any insight into these concerns and addresses the different BMI criteria between the studies.
How do the duration and different BMI criteria of SURPASS-CVOT address concerns about the long-term practicality of GLP-1–based weight-loss therapies?
This is a long trial, and with long trials, we need to work closely with patients in the sites to make sure that patients continue to take their study drug [and] continue to come for all their visits so that we can get as accurate a follow-up for them as possible. We know that study fatigue can happen over the course of a really long trial, so we work really closely with our patients in our sites accordingly. These agents, whether you look at dulaglutide, which is the comparator, or tirzepatide, which is the agent that we're investigating in this trial, we know that they will be associated with GI [gastrointestinal] intolerance, in particular nausea. We work really closely with our sites and our patients to help manage through that. We know that some patients will either require a down titration of dose or having to come off study drug completely for periods of time. And again, we work closely, because we know that that's a relationship that we need to maintain over a long period of time. Certainly, there's a theoretical chance that if a patient were to come off study drug permanently, then any perceived weight loss may be regained again. When you do these long trials, we always see patients coming off study drug as essentially a temporary thing, so wherever possible, we want to try and get patients back on to study drug. That's not always possible with patients, but it really then reinforces that idea that we ask our sites to be really in constant communication with the patients.
There are BMI differences in terms of the study entry criteria for the SURPASS-CVOT, which is a study that's looking at cardiovascular outcomes in patients with type 2 diabetes, and the SURMOUNT studies, which are really looking at the effect of tirzepatide on weight loss in patients with obesity or who are overweight, where they don't have type 2 diabetes. So they're 2 very different types of questions. And so it's not that surprising that studies that are being done exclusively from a weight loss perspective are going to have to have a body mass index entry of at least 27, whereas, given that SURPASS is really a type 2 diabetes study, it's a slightly lower body mass index. Will that have an impact in terms of weight loss that we see? We don't believe so. Overall, we think that will all be good for patients but we have to wait and see the results.