The U.S. Food and Drug Administration has expanded the indication of Novo Nordisk’s well-known glucose-lowering therapy, now authorizing its use for individuals with both Type 2 diabetes and chronic kidney disease (CKD). This regulatory approval marks a critical advancement in the management of CKD, addressing a major comorbidity that significantly elevates mortality risk among diabetic patients.
Previously prescribed primarily for blood sugar regulation, the medication can now be utilized to decelerate renal deterioration, mitigate the probability of kidney failure, and lower the incidence of cardiovascular-related mortality in individuals affected by both conditions.
This development represents a fundamental shift in the clinical approach to CKD, a progressive disease that impairs renal function over time and remains one of the most significant contributors to morbidity and mortality in the United States. Data from Novo Nordisk indicate that approximately 37 million adults in the country live with some form of CKD.
Diabetes remains a predominant risk factor for kidney impairment, with nearly 40% of individuals diagnosed with Type 2 diabetes eventually developing renal dysfunction. Beyond its direct impact on kidney function, CKD is associated with an increased likelihood of cardiovascular complications, further exacerbating health risks in this population.
Stephen Gough, MD, global chief medical officer at Novo Nordisk, emphasized that CKD is inherently a progressive condition characterized by a relentless decline in renal filtration capacity. In its advanced stages, individuals often require renal replacement therapies, such as dialysis or transplantation, both of which present significant clinical and logistical burdens. Mortality rates remain high in end-stage renal disease, particularly due to cardiovascular complications.
This FDA approval further reinforces the emerging role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in managing chronic metabolic and systemic conditions beyond their traditional indications in glycemic control and weight regulation.
The decision follows a pivotal phase 3 clinical trial that demonstrated the therapy’s ability to reduce the risk of severe renal outcomes—including progression to end-stage kidney disease, rapid decline in glomerular filtration rate, or death from renal or cardiovascular causes—by 24% compared to a placebo in individuals with concomitant diabetes and CKD.
Additionally, participants receiving the therapy exhibited an 18% reduction in major adverse cardiovascular events, including myocardial infarction and stroke, alongside a 20% reduction in all-cause mortality. Notably, the therapy also conferred a 29% reduction in cardiovascular-specific mortality.
Dr. Gough underscored the intrinsic link between cardiovascular pathology and renal dysfunction, highlighting that current treatment strategies for CKD in its early stages often prioritize cardiovascular risk reduction, including stringent blood pressure control.
The study further reported that 49.6% of individuals receiving the therapy experienced serious adverse events, a slightly lower incidence than the 53.8% observed in the placebo cohort. While gastrointestinal-related side effects such as nausea and vomiting were more prevalent among those receiving the medication, these effects are consistent with the established safety profile of GLP-1 receptor agonists.
Regulatory agencies in the European Union approved the expanded indication for this therapy in December, aligning with the growing global recognition of its therapeutic benefits.
The phase 3 trial, known as FLOW, was initiated in 2019 and involved approximately 3,500 participants with Type 2 diabetes and moderate-to-severe CKD. Novo Nordisk discontinued the trial a year ahead of schedule in October, citing overwhelmingly positive interim results. This announcement triggered a substantial decline—nearly 20%—in the stock valuation of major dialysis providers, reflecting investor expectations that a greater proportion of patients may avoid dialysis in the future.
Dr. Gough emphasized the broader clinical implications of this development, noting that conditions such as diabetes, obesity, CKD, and cardiovascular disease frequently co-exist in patients. He suggested that a single therapeutic intervention capable of addressing multiple overlapping disease pathways represents a paradigm shift in chronic disease management.
The FDA’s decision coincides with the Biden administration’s efforts to regulate pharmaceutical pricing, with this therapy—alongside two additional Novo Nordisk products containing the same active ingredient—being included in the second cycle of Medicare negotiations.
Simultaneously, Novo Nordisk continues to navigate increased competition from Eli Lilly while advocating for expanded insurance coverage of its weight management formulation. In 2023, the company secured FDA approval for its weight loss formulation to reduce the risk of major cardiovascular events, such as myocardial infarction and stroke, and is now investigating its potential utility in managing metabolic-associated fatty liver disease.
This regulatory milestone further establishes GLP-1 receptor agonists as a cornerstone therapy for addressing interrelated chronic conditions, reflecting a significant advancement in the field of cardiometabolic and renal medicine.