Semaglutide 2.4 mg approved to prevent CV events in patients with overweight, obesity

Erin D. Michos, MD, MHS, FACC, FAHA, FASE, FASPC

Obesity is a serious life-threatening disease. It's strongly associated with increased CV risk and not just atherosclerotic CV risk, but HF, atrial fibrillation, and the list goes on. It just hasn't gotten the same level of attention as treating other CV risk factors like BP and lipids. There has been a lot of stigma around persons living with overweight and obesity.

We already knew these agents reduced CV risk in persons with type 2 diabetes, and the SELECT trial was a game changer because it showed, in these high-risk secondary prevention patients who had CVD with overweight and obesity, that weight reduction through GLP-1 receptor agonists reduces major CV outcomes. These are our endpoints, as cardiologists. These are our events.

In fact, SELECT was not a weight-loss trial per se, it was a CV outcome trial. We should be framing how we're thinking about these agents in terms of CV risk, both for health care practitioners to recognize and understand the importance of GLP-1 receptor agonist therapy for cardiovascular risk reduction and helping them motivate and support patients in losing weight.

There's already been explosion of use of these medications. The big challenge is payers. Insurance companies sometimes have complete carve-outs where you can't even appeal. They won't even cover weight loss medications on the formulary. This has been challenging, because there are patients I've had with overweight and obesity with weight-related comorbidities that would really benefit from this therapy. They already met the prior indication for semaglutide 2.4 mg, but their insurance had carve-outs.

I'm hoping with this new indication that they can no longer have these carve-outs, when you have a therapy that's indicated for reduction of CV death, heart attacks and strokes, and I'm hoping that this pushes the payers to cover these medications.

Something we've been running into is the issue of nationwide shortages. Hopefully since supplies have been ramped up, that will improve the situation.

There are still some remaining questions. SELECT was a secondary prevention trial. So whether you would see the same or similar reduction in major adverse CV outcomes in persons with overweight and obesity who don't have established CVD remains to be seen. I'm certainly optimistic already. In secondary analysis of prior weight loss studies, such as STEP and SCALE, when cardiovascular events were pooled together for safety, we saw a trend for reduction in events in that population.

The ongoing SURMOUNT MMO trial is also going to be important. Right now, semaglutide is the only one in this class that has demonstrated CV risk reduction in persons that don't have diabetes but have overweight and obesity. SURMOUNT MMO is evaluating tirzepatide (Zepbound, Eli Lilly) in persons with overweight and obesity without diabetes, but not only do they include people with CVD, they're also including people at high CV risk.

There are still some remaining questions, but the important thing is that we're changing the narrative around obesity and overweight. For so long, this has been considered a lifestyle disease, and there's just been a lot of blame put on the individuals. That is crazy, because we don't do that for other risk factors. We know it's far more complicated than just individual choices.

It is exciting that we now have effective therapies that we can offer patients, but we need to make sure that they're available and that they're covered by insurance, just like other CV prevention agents. This new label indication is important because this is no longer just labeled for weight reduction. This is a separate label specifically for CV risk reduction, and that changes the narrative.