Commentary
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Author(s):
Semaglutide has been approved for reducing kidney disease progression and cardiovascular risk in patients with type 2 diabetes, marking a significant advancement in CKD management.
In an interview with Pharmacy Times®, Pranav Garimella, MD, chief medical officer of the American Kidney Fund and board-certified nephrologist at UC San Diego Health, discusses what the recent FDA approval of semaglutide (Ozempic, Wegovy; Novo Nordisk), a glucagon-like peptide-1 receptor agonist (GLP-1 RA) to reduce kidney disease and cardiovascular death risk in adults with type 2 diabetes (T2D) and chronic kidney disease (CKD) means for patients in this population. Garimella explains the efficacy data behind semaglutide's approval and elaborates on the mechanism of action behind the demonstrated reductions in kidney disease progression and cardiovascular events.
Pharmacy Times: What does the approval of semaglutide to reduce the risk of death from kidney disease in CKD mean for patients in this population?
1. Semaglutide slows kidney disease progression and reduces cardiovascular events, addressing the leading causes of death in CKD patients with T2D.
2. Beyond glucose and blood pressure control, its anti-inflammatory and vascular-protective effects contribute to its cardiovascular and kidney benefits.
3. Semaglutide is expected to become a core treatment alongside RAS inhibitors, SGLT2 inhibitors, and mineralocorticoid RAs in managing CKD-related complications.
Pranav Garimella, Chief Medical Officer, American Kidney Fund: Semaglutide is an exciting new drug that has just been approved by the FDA for managing and preventing kidney disease progression in patients with type 2 diabetes (T2D). This is an exciting new development, and the kidney community really views the results of the FLOW trial that this approval was based on as an important milestone and a new therapeutic adjunct that we can actually use in the management of CKD, especially in this very high-risk T2D population that we often see. It isn't just kidney failure progression that was stopped; it was cardiovascular disease events, which are the number 1 cause of death in these patients. And so actually, being able to slow both kidney disease and cardiovascular disease is, I think, a critical advancement in helping take care of this patient population.
Pharmacy Times: Could you explain how semaglutide’s mechanism of action works to reduce the risk of death in patients with CKD?
Garimella: Semaglutide belongs to a class of drugs known as GLP-1 receptor agonists (RAs), and they've demonstrated a reduction in cardiovascular morbidity and mortality, in addition to weight loss and blood glucose control. In addition to these, GLP-1 RAs really have a variety of effects across the metabolic and vascular systems. They have anti-inflammatory effects. They have antithrombotic effects. It's also thought that they can stabilize plaques in these blood vessels, leading to a less atherogenic systemic environment. What this does is reduce the [overall] burden of cardiovascular disease, and that could be one of the reasons why patients with diabetes, and even CKD, actually end up having fewer cardiovascular events when taking GLP-1 RAs. More recently, there was a large meta-analysis of several trials that showed up to a 15% reduction of these major cardiovascular events. So, this is a really exciting new development in the field.
Pharmacy Times: How does semaglutide differ from standard CKD treatments? Could semaglutide one day become a standard of care option for CKD?
Garimella: Historically, CKD treatments have really focused on managing the underlying causes. That would typically be treatment of diabetes, treatment of high blood pressure, and even high cholesterol levels. While GLP-1 RAs like semaglutide influence glucose control and blood pressure management, the benefits seem to be out of proportion to what we see just on glucose and blood pressure. I think that relates back to some of the other non-blood pressure and glucose effects that I just spoke about. The results of semaglutide in CKD, therefore, really offer a promise that treatment strategies could have vast effects across the cardiovascular system, and we could reshape and use some of these medications not just to treat diabetes but actually to prevent the cardiovascular complications and heart failure complications that we see. It's very likely that, along with renin-angiotensin system (RAS) inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid RAs, semaglutide, or GLP-1 RAs, could essentially become the fourth pillar in managing T2D and cardiovascular complications from it. I'm hoping that as we get more data on patients with diabetes and CKD, we start incorporating the use of GLP-1 RAs into our guideline-directed therapy for managing these patients.
