Recently, the U.S. Food and Drug Administration (FDA) approved Ozempic® (active ingredient semaglutide) as the only GLP-1 receptor agonist to reduce the risk of worsening kidney disease and cardiovascular death in adults with type 2 diabetes and chronic kidney disease.
We sat down with Ryan Singerman, DO, PPG - Family Medicine and Internal Medicine, to gain a deeper understanding of what this new indication means in practice and how the numbers behind it translate to real-world impact for individuals living with these comorbidities.
What the numbers say
The data behind the FDA's approval is based on the results from the Novo Nordisk FLOW phase 3b kidney outcomes trial. The study spanned over three years involving adult participants diagnosed with diabetes and chronic kidney disease (CKD). The trial results indicated that, when combined with standard care, participants who used Ozempic for 3.4 years experienced a 24% reduction in their relative risk of chronic kidney disease progression compared to those receiving a placebo.
With that being said, there are a few points to clarify:
Limitations to replication - All participants in this trial were diagnosed with moderate to severe chronic kidney disease (Stage 3b), which means that the data is based on a specific population and may not yield the same results for individuals diagnosed with CKD and diabetes at other stages.
Number Needed to Treat (NNT) - NNT is a statistic that indicates how many patients need treatment to prevent one bad outcome or achieve one positive result.
The challenge of relative risk - There are many ways to present clinical trial data, and some are more attention-grabbing than others. Two methods utilized in this study were:
-
Relative risk - compares the likelihood of an event occurring in an exposed group to that in a non-exposed group within the study's parameters.
-
Absolute (actual) risk - refers to the real-world probability of an event occurring in a specific population or individual over a defined period. This information is typically more meaningful for patients and providers, especially when determining the most effective treatment options.
Putting it in perspective
Kidney function naturally declines with age. According to the Centers for Disease Control and Prevention (CDC), after age 40, kidney filtration begins to decline by approximately 1% each year. This number can vary based on several factors, including genetics, lifestyle and health conditions like diabetes, hypertension and heart disease.
In individuals diagnosed with type 2 diabetes, the absolute risk of CKD progression is approximately 7.5% per year, assuming no effort is taken to intervene.
Again, in the trial that led to the FDA's approval, researchers found that semaglutide administered along with standard treatment resulted in a 24% relative risk reduction over 3.4 years. The absolute risk reduction was 4.9% over 3 years, which equates to a 1.6% reduction per year. This brings the baseline line progression for people with type 2 diabetes from 7.5% to 5.9% (or from 92.5% likelihood of progressing to 94.1%).
How does this compare?
CKD treatment is based on the underlying cause and the severity or stage it has progressed to, but it typically involves a combination of lifestyle modifications and pharmaceutical interventions. Another class of medications also approved for treating type 2 diabetes and reducing the risk of cardiovascular and kidney events are SGLT-2 inhibitors. Brand-name drugs like Jardiance® and Farxiga® fall into this category. They work by preventing the kidneys from reabsorbing glucose into the bloodstream. Instead, excess glucose is excreted through urine, resulting in lowered blood sugar levels.
In another 2021 report, independent researchers conducted a meta-analysis of 13 previously published studies. This examination aimed to compare the cardiovascular and renal outcomes of SGLT-2 inhibitors and GLP-1 receptor agonists in patients with type 2 diabetes mellitus and chronic kidney disease.
When comparing the relative risk reductions between the two studies (the FLOW trial and SGLT-2 meta-analysis), the SGLT-2 class drugs administered orally once daily were considerably better at reducing the relative risk of kidney events compared to the GLP-1s.
-
GLP-1s: To reduce the risk of chronic kidney disease in one person, 22 individuals must receive treatment for 3.4 years at an approximate monthly cost of $1000* per patient.
-
SGLT-2s: To achieve the same outcome, 18-19 people must receive treatment for 2.5 years at an approximate monthly cost of $600* per patient.
*The above costs are based on current market prices for the indicated drug classes. These estimates do not include insurance coverage or manufacturer discounts.
Final thoughts
Compared to other treatments, GLP-1 medications do offer some improvement in reducing the risk of CKD progression, but their benefits are not as significant as advertised. On an individualized basis, there may be interventions better suited for some patients.
The good news is that we are already recommending them for people with type 2 diabetes for a host of reasons. While it's helpful to see more evidence supporting the benefits of these therapies, this does not mean that more people should necessarily be on this medicine.
Beyond the headlines and clinical trial results, treating chronic diseases requires an individualized approach with providers who are familiar with your health history and goals. To establish care with a PPG – Family Medicine provider, schedule online or call our 24/7 scheduling center at 877-774-8632.
