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Focus on SGLT2 inhibitors like Farxiga

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In August 2023, we published an in-depth article that focused on a significant improvement in the treatment of both heart and kidney diseases coming from the widespread introduction of new diabetes medications that are based on GLP-1 (glucagon-like peptide-1) receptor agonists (such as Ozempic, Semaglutide, and Mounjaro.) One of our readers posted a question as to whether other new diabetes medications that are based on SGLT2 inhibitors (such as Farxiga) can produce results similar results. While we briefly mentioned SGLT2i in the original article, we would like to revisit the conversation now and provide a bit more focus on Farxiga and other similar drugs.

For more details on GLP-1, please see “Mounjaro is hot news, for good reason,” “Your guide to compounded medications” and “Good News about Semaglutide Side Effects)”. These each offer insight into how GLP-1-based drugs have revolutionized treatments in several fields, including diabetes, obesity, heart disease, and kidney failure.

How do Farxiga and other SGLT2i drugs work?

Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a class of drugs that originally gained approval for treating type 2 diabetes but, since their introduction, have shown good secondary benefits for both cardiac and renal (kidney) health. For more background information, see “FDA approval of Farxiga for treatment of heart failure” and “FDA approves a new type 2 diabetes drug that works in combination with Metformin”.

Research into SGLT2 inhibitors began with understanding the role of the SGLT2 protein in the kidneys in reabsorbing glucose back into the bloodstream. Farxiga (generic name: dapagliflozin) was the second SGLT2i drug approved for diabetes in the mid-2010s, based on trials of their use in treatments for type 2 diabetes that proved their effectiveness in lowering blood glucose levels in type 2 diabetes patients.

Dapagliflozin and the other SGLT2 inhibitors were reported to show significant secondary benefits for diabetic patients, and the drug manufacturers undertook several trials to try and follow through on these reports. The first was the EMPA-REG OUTCOME trial in 2015, which demonstrated that empagliflozin (sold under the brand name Jardiance) not only helped manage blood sugar levels but also led to significant reductions in hospitalizations for heart failure and deaths caused by cardiovascular disease. In 2016, following these trials, the FDA expanded the labeling of Jardiance to include its beneficial effects on heart health. This was the first time that an anti-diabetic medication received approval for cardiovascular benefits.

In May 2020, based on the results of the DAPA-HF trials conducted on the effectiveness of dapagliflozin in cardiovascular outcomes, the FDA approved Farxiga as a treatment to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with the specific form of heart failure known as reduced ejection fraction. This approval is not as broad as the cardiovascular approval for Jardiance.

In April 2021, the FDA extended the approval of Farxiga as a drug that reduces the risk of kidney function decline and kidney failure, as well as cardiovascular death and hospitalization for heart failure in adults with chronic kidney disease who are at risk of disease progression regardless of diabetes status. You can read much more about the special features of SGLT2 relating to kidney functions on the National Institute of Diabetes and Digestive and Kidney Diseases website.

What are SGLT2 inhibitors such as Farxiga?

SGLT2 inhibitors block glucose reabsorption in the kidneys, leading to its excretion in urine. In doing so, they help to lower blood glucose levels. It’s a different pathway than GLP-1 receptor agonists, but the effect of gaining better control over blood sugar is similar.

How do GLP-1 receptor agonists help people with kidney or heart problems?

GLP-1 receptor agonists do not just control sugar levels in the blood. The drug has multiple benefits, including reducing cardiac stress, improving renal function, and promoting weight loss.

Questions people ask

How do SGLT2 inhibitors work?

SGLT2 inhibitors function by reducing renal tubular glucose reabsorption. This produces a reduction in blood glucose levels without stimulating insulin release. Other benefits can include positive effects on blood pressure, renal functions, and weight.

What are some examples of GLP-1 inhibitors?

Diabetes drugs in the GLP-1 agonists class are generally taken by injection, either daily or weekly. They include Trulicity (dulaglutide), Ozempic (semaglutide), Mounjaro (tirzepatide), and Semaglutide (compounded)

Which organ do SGLT2 inhibitors target?

Sodium-glucose co-transporter type 2 (SGLT2) inhibitors target the kidney tubules. They reduce renal glucose reabsorption and increase urinary glucose elimination, which lowers glucose blood levels. SGLT2 inhibitors are effective at reducing risk factors like heart disease, stroke and slowing the progression of kidney disease and kidney failure leading to death in people with CKD who develop type 2 diabetes.

Is metformin similar to Ozempic?

Semaglutide and metformin are both medications prescribed to treat type 2 diabetes. Ozempic is a weekly injection approved for adults. Metformin is an oral medication approved for ages ten and older. They work in different ways to lower blood glucose levels.

Is SGLT2 inhibitor a diuretic?

Sodium-glucose cotransporter 2 (SGLT2) inhibitors exert both hypoglycemic and diuretic effects by inhibiting the absorption of both sodium and glucose from the proximal tubules in the kidney. Patients usually report that SGLT2i medications increase urinary volume.

What is the difference between SGLT1 and SGLT2?

SGLT2 is active primarily in the kidneys, where it blocks the reabsorption of glucose. In this way, it is dependent on kidney function. SGLT1 does not depend on kidney function because it is active in the gut as the primary transporter of glucose and galactose.

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