Disclaimer: This post is provided for informational purposes only and does not reflect the personal perspective or opinions of any naturopath. The content herein simply relays current medical research findings and should not be construed as medical advice or a naturopathic recommendation. Medications are outside of the scope of naturopathic medicine in Ontario, Canada.
While modern research has demonstrated that empagliflozin (marketed as Jardiance) offers significant benefits for individuals with type 2 diabetes and chronic kidney disease (CKD), research has found that some patients may have an initial drop in kidney function. This post explains this phenomenon and discusses the long-term outcomes. When possible, this post places priority to large-scale, multinational studies conducted by diverse groups of independent researchers—to help ensure that the findings are robust and widely applicable.
What Is Jardiance?
Jardiance is the brand name for empagliflozin, a medication in the class of sodium–glucose cotransporter 2 (SGLT2) inhibitors. Originally approved to manage hyperglycemia in patients with type 2 diabetes, Jardiance has become notable for its additional benefits on kidney function and cardiovascular health.
Key Points:
Primary Role in Diabetes:
Jardiance works by blocking SGLT2 proteins in the kidneys, thereby reducing the reabsorption of glucose and allowing it to be excreted in the urine.
Renal Benefits:
Research shows that empagliflozin can slow the progression of CKD, reduce albuminuria (protein in the urine), and even delay the need for dialysis.
Cardiovascular Effects:
Studies have consistently demonstrated a reduction in cardiovascular death and hospitalization for heart failure among patients taking Jardiance.
Wide Applicability:
Importantly, benefits have been observed in patients both with and without diabetes, as highlighted by recent trials such as EMPA-KIDNEY (2022) and EMPA-REG OUTCOME (2015).
How Jardiance Works in the Body and for the Kidneys
Understanding the mechanism of Jardiance helps clarify how it exerts its positive effects on both blood sugar control and kidney health.
Mechanism of Action:
SGLT2 Inhibition:
By inhibiting the SGLT2 protein, empagliflozin reduces the reabsorption of glucose in the proximal tubules of the kidney. This leads to increased excretion of glucose (glycosuria) and a lowering of blood sugar.
Tubuloglomerular Feedback:
The increased delivery of sodium to the macula densa (a specialized part of the kidney) helps restore tubuloglomerular feedback. This process causes a temporary decrease in glomerular filtration rate (GFR) known as the “acute dip.”
Hemodynamic Changes:
Rather than causing structural damage, the initial drop in GFR is due to reversible hemodynamic changes—a shift in blood flow within the kidney. These changes lower intraglomerular pressure, reducing stress on the filtering units of the kidneys.
Long-Term Stabilization:
After the initial dip, the decline in GFR slows considerably, leading to better preservation of kidney function over time. This effect has been quantified in studies that demonstrate a significant reduction in the annual rate of eGFR decline (2022).
Does Jardiance Damage the Kidneys?
A common concern among patients is whether an initial decline in kidney function might indicate damage. The research shows otherwise.
Key Points:
Reversible Hemodynamic Changes:
The initial decrease in eGFR is due to changes in blood flow and pressure within the kidneys rather than permanent structural damage.
Long-Term Kidney Protection:
Once the body adapts, the chronic decline in kidney function is significantly slowed. This “reset” of kidney hemodynamics is beneficial and protective.
Robust Research Support:
Findings from multiple studies, including the EMPA-KIDNEY trial, confirm that empagliflozin is renoprotective rather than harmful.
What is the “Reset” or Dip?
In simple terms, the eGFR "dip" is a temporary drop in kidney function (measured by estimated glomerular filtration rate, or eGFR) that happens when certain treatments are started. This dip is not a sign of harm but rather an expected response to medications that protect the kidneys.
Why Does This Happen?
In chronic kidney disease (CKD), the kidneys often overwork in the early stages due to increased pressure in the small filtering units (glomeruli). This overwork can eventually cause damage.
Some medications (like ACE inhibitors, ARBs, and SGLT2 inhibitors) help by reducing this pressure, slowing further kidney damage.
When the pressure drops, the kidneys initially filter less blood, leading to a short-term drop in eGFR—this is the "dip."
Is the Dip Bad?
No, studies show that this dip is usually temporary and reversible.
In the long run, people who experience a greater dip tend to have better kidney protection over time.
Some doctors initially worried that the dip meant the drugs might harm the kidneys, but research has shown these medications actually protect the kidneys and heart in the long term.
Here’s a graph showing the change in kidney function over time from a 2022 study by the New England Journal of Medicine, which found greater kidney function in the group taking empagliflozin (jardiance) than placebo:
Does Empagliflozin Improve Kidney Function?
Multiple clinical trials have examined the effects of empagliflozin on kidney function, with promising results.
Key Findings:
Reduction in Kidney Disease Progression:
The EMPA-KIDNEY trial, which included over 6600 patients with CKD, found that empagliflozin reduced the composite outcome of kidney disease progression or cardiovascular death by about 28% compared with placebo (2022).
eGFR Slope Improvement:
Studies show that after the initial reversible dip in eGFR, the chronic rate of decline is significantly slower in patients treated with Jardiance. For instance, one analysis demonstrated a 50% reduction in the rate of chronic eGFR decline.
Broad Benefit Across Patient Types:
Notably, these kidney-protective effects have been observed in patients with both diabetic and non-diabetic CKD, reinforcing the idea that empagliflozin benefits a wide range of individuals.
Highlights from Research:
EMPA-REG OUTCOME (2015 & 2016):
These trials not only underscored cardiovascular benefits but also provided evidence that empagliflozin can slow the deterioration of kidney function.
Meta-analyses:
Large meta-analyses of SGLT2 inhibitor trials indicate a consistent reduction in the risk of major kidney events, suggesting a class effect.
Impact on Cardiovascular Health
Jardiance’s benefits extend well beyond the kidneys; its impact on cardiovascular health is also significant.
Cardiovascular Benefits:
Reduced Risk of Cardiovascular Death:
Empagliflozin has been shown to reduce cardiovascular death by approximately 38% in high-risk patients, as seen in the EMPA-REG OUTCOME trial (2015).
Lower Hospitalizations for Heart Failure:
Patients taking Jardiance experience fewer hospitalizations due to heart failure.
All-Cause Mortality:
Overall, empagliflozin contributes to a reduction in all-cause mortality, likely because of its combined kidney and heart benefits.
Mechanistic Insights:
Hemodynamic Modulation:
By reducing blood pressure and alleviating cardiac workload through diuretic effects, empagliflozin helps improve cardiovascular outcomes.
Consistent Effects Across Subgroups:
Research indicates that the cardiovascular benefits are present regardless of the presence or absence of diabetes, highlighting the drug’s broad utility.
Side Effects
While Jardiance is generally well tolerated, it is important to be aware of potential side effects.
Common Side Effects:
Urinary Tract Infections: A slightly increased risk has been observed.
Safety Profile:
Pooled analyses, such as those reported in 2022, indicate that most side effects are mild and manageable.
How Long Does It Take Jardiance to Improve Kidney Function?
Understanding the timeline of treatment can help set realistic expectations for patients.
Timeline Overview:
First Few Weeks:
An acute drop in eGFR occurs soon after treatment initiation.
This phase is marked by the hemodynamic “reset” discussed above.
After Two Months:
The acute effects wear off, and the chronic phase begins.
The rate of eGFR decline slows considerably compared with placebo.
Long-Term Outlook:
Over years, empagliflozin’s benefits on kidney function translate into fewer adverse kidney events and delayed progression to end-stage kidney disease.
Supporting Data:
The EMPA-KIDNEY trial (2022) showed that, after an initial dip, the difference in chronic eGFR slope between empagliflozin and placebo was about 1.37 mL/min/1.73 m² per year—a 50% reduction in decline rate.
Addressing Concerns About Research Sponsorship and Methodology
It is understandable for patients to be cautious about the influence of industry sponsorship on clinical research. However, several factors help to ensure the reliability and transparency of these studies.
Assuring Research Quality:
Multinational, Large-Scale Trials:
Studies like EMPA-KIDNEY and EMPA-REG OUTCOME involved thousands of patients across multiple countries. This diversity minimizes regional biases and enhances the generalizability of the findings.
Independent Oversight:
These trials are overseen by independent data and safety monitoring committees that review unblinded data to safeguard participant well-being.
Robust Peer Review:
The findings are published in high-impact, peer-reviewed journals such as the New England Journal of Medicine and The Lancet, ensuring that the research methods and conclusions are scrutinized by experts.
Transparency in Data Sharing:
Many study sponsors now have policies for data sharing, allowing independent researchers to verify the results.
Combination of Academic and Industry Efforts:
While some studies are industry-sponsored, they are conducted in collaboration with academic institutions and independent researchers, which helps balance potential conflicts of interest.
Final Thoughts
Kidneys are complex - and their relationship with common medications are not always straight forward, however overall the evolving research on Jardiance (empagliflozin) paints an encouraging picture for patients with chronic kidney disease. Key clinical trials such as EMPA-KIDNEY and EMPA-REG OUTCOME have demonstrated that empagliflozin can slow the progression of kidney disease, reduce the risk of cardiovascular events, and ultimately improve long-term outcomes. Although an initial dip in kidney function may occur when starting treatment, this is a normal, reversible hemodynamic effect rather than an indication of kidney damage. Over time, the benefits of slower eGFR decline, lower albuminuria, and reduced hospitalization rates translate into a delay in the onset of end-stage kidney disease and better overall cardiovascular health.
For those considering Jardiance, it is crucial to understand that while the initial changes in kidney function can be concerning, they represent an adaptive response that ultimately leads to improved outcomes. Regular monitoring and close collaboration with healthcare providers are essential to ensure that treatment is optimized and any adverse effects are managed appropriately.
As research continues to unfold, the consistent findings from large, multinational trials offer reassurance that SGLT2 inhibitors like empagliflozin are not only safe but also a valuable addition to the standard of care for CKD. These results have significant implications for clinical practice, potentially reducing the future global burden of kidney failure and its associated complications.
This post is intended solely for educational purposes. For any decisions regarding treatment or changes to your healthcare regimen, please consult a qualified healthcare professional.
By staying informed through reliable, peer-reviewed research, patients and providers can work together to optimize kidney health and overall well-being in the face of chronic disease.
