Farxiga/Forxiga: Drug for Diabetes, Heart Failure and Kidney Disease

Farxiga is a brand name in the United States and Forxiga is the brand name in Europe and other countries. It is a tablet that belongs to a class of medicines called SGLT2 inhibitors, which work by removing excess sugar from your body through urine. Farxiga has been shown to improve blood sugar control, reduce the risk of hospitalization for heart failure, and slow down the progression of kidney disease in people with and without diabetes. In this blog post, we will explore what Forxiga is, how it works, who can use it, and what are its benefits and side effects.

What is the Mechanism of Forxiga/Farxiga?

Forxiga is the brand name of dapagliflozin, a drug that was developed by AstraZeneca in partnership with Bristol-Myers Squibb. It is available as 5 mg or 10 mg tablets that are taken once daily in the morning. Forxiga works by blocking a protein called SGLT2 in the kidneys, which normally reabsorbs glucose and sodium from the urine back into the bloodstream. By inhibiting SGLT2, Forxiga prevents glucose and sodium reabsorption and increases their excretion in the urine. This lowers the blood glucose levels and reduces the workload on the kidneys. It also reduces the fluid retention and blood pressure in the body, which can improve the function of the heart and blood vessels.

Approval of Forxiga/Farxiga

Forxiga is approved for different indications depending on the country and region. In general, Forxiga can be used for the following purposes:

• To improve blood sugar control in adults with type 2 diabetes mellitus (T2DM) who are not adequately controlled by diet and exercise alone or by other antidiabetic medicines. Forxiga can be used as monotherapy or in combination with other antidiabetic agents, such as metformin, sulfonylureas, insulin, or GLP-1 receptor agonists.

• To reduce the risk of hospitalization for heart failure in adults with T2DM and established cardiovascular disease (CVD) or multiple cardiovascular risk factors, such as high blood pressure, high cholesterol, or smoking. Forxiga can be used in addition to standard of care treatment for CVD, such as angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers, or statins.

• To reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). Forxiga can be used regardless of diabetes status and in addition to standard of care treatment for heart failure, such as ACEIs, ARBs, beta-blockers, diuretics, or mineralocorticoid receptor antagonists (MRAs).

• To reduce the risk of sustained decline in kidney function, end-stage kidney disease (ESKD), cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease (CKD) who are at risk of progression. Forxiga can be used regardless of diabetes status and in addition to standard of care treatment for CKD, such as ACEIs or ARBs.

Table 1: Approval of Forxiga/Farxiga
Country	T2DM	HFrEF	CKD	HFpEF
US	2014	2020	2021	2021
Europe	2012	2020	2021	2021
Japan	2014	2020	2021	2021
China	2014	2020	2022	2023

What are the benefits of Forxiga/Farxiga?

Forxiga has been tested in several clinical trials involving thousands of patients with different conditions. The results have shown that Forxiga can provide significant benefits for people with T2DM, heart failure, and CKD. Some of the main findings are summarized below:

• In patients with T2DM who were not adequately controlled by other antidiabetic medicines, adding Forxiga to their regimen improved their blood sugar levels (measured by HbA1c), body weight, blood pressure, and cholesterol levels compared to placebo. Forxiga also reduced the risk of major adverse cardiovascular events (MACE), such as heart attack, stroke, or cardiovascular death.

• In patients with T2DM and established CVD or multiple cardiovascular risk factors, taking Forxiga reduced the risk of hospitalization for heart failure by 27% compared to placebo. This benefit was consistent across different subgroups of patients based on age, sex, race, renal function, history of heart failure, or use of other medications.

• In patients with heart failure with reduced ejection fraction (HFrEF), taking Forxiga reduced the risk of worsening heart failure or cardiovascular death by 26% compared to placebo. This benefit was seen in patients with and without diabetes and across different subgroups of patients based on age, sex, race, renal function, or use of other medications. Forxiga also improved the symptoms and quality of life of patients with heart failure.

• In patients with chronic kidney disease (CKD) who were at risk of progression, taking Forxiga reduced the risk of worsening kidney function, end-stage kidney disease, cardiovascular death, or hospitalization for heart failure by 39% compared to placebo9. This benefit was seen in patients with and without diabetes and across different subgroups of patients based on age, sex, race, renal function, or use of other medications. Forxiga also reduced the risk of death from any cause by 31% compared to placebo.

What are the side effects of Forxiga/Farxiga?

Like any medication, Forxiga may cause some side effects in some people. The most common side effects of Forxiga are genital infections, urinary tract infections, increased urination, nausea, vomiting, constipation, dizziness, and rash. These side effects are usually mild and may go away with time or with proper hygiene measures. However, if they persist or worsen, you should contact your doctor.

Some rare but serious side effects of Forxiga include ketoacidosis, dehydration, low blood sugar (hypoglycemia), low blood pressure (hypotension), acute kidney injury, and Fournier’s gangrene. Ketoacidosis is a condition where the body produces too much acid in the blood due to insufficient insulin or glucose. It can cause symptoms such as nausea, vomiting, abdominal pain, difficulty breathing, confusion, or coma. Dehydration is a condition where the body loses too much fluid due to increased urination or other causes. It can cause symptoms such as thirst, dry mouth, weakness, dizziness, or fainting. Low blood sugar (hypoglycemia) is a condition where the blood glucose level drops below normal due to excessive insulin or glucose-lowering medication. It can cause symptoms such as sweating, shaking, hunger, headache, blurred vision, or loss of consciousness.

Low blood pressure (hypotension) is a condition where the blood pressure falls below normal due to fluid loss or other causes. It can cause symptoms such as lightheadedness, drowsiness, or fainting. Acute kidney injury is a condition where the kidney function suddenly declines due to reduced blood flow or damage to the kidney cells. It can cause symptoms such as decreased urine output, swelling of the legs or feet, shortness of breath, fatigue, or confusion. Fournier’s gangrene is a rare but serious infection of the genital area that can spread rapidly and cause tissue death. It can cause symptoms such as fever, pain, swelling, redness, or foul-smelling discharge in the genital area.

If you experience any of these serious side effects or any signs of an allergic reaction (such as rash, itching, swelling of the face or throat, or difficulty breathing), you should stop taking Forxiga and seek medical attention immediately.

Price of Forxiga/Farxiga

Forxiga is available in different countries and regions under different brand names and prices. In the US, it is sold under the brand name Farxiga and costs about $604 for a 30-day supply of 10 mg tablets. In the UK, it is sold under the brand name Forxiga and costs about £174.99 for a 28-day supply of 10 mg tablets. Forxiga costs about €56 for a 28-day supply of 10 mg tablets in Italy. In Japan, it is sold under the brand name Forxiga and costs about ¥7,000 for a 28-day supply of 10 mg tablets.

Reimbursement of Forxiga/Farxiga 

Forxiga is a medication that can treat type 2 diabetes, heart failure, and chronic kidney disease in adults. Forxiga is approved in different countries and regions for different indications and has different prices. Therefore, the reimbursement of Forxiga may also differ depending on where you live and what condition you have.

United States

Forxiga is reimbursed by various insurance plans and programs for the treatment of type 2 diabetes mellitus, heart failure with reduced ejection fraction, chronic kidney disease, and heart failure with preserved ejection fraction. The reimbursement of Forxiga may depend on your insurance plan, your copay, your deductible, and your eligibility for savings programs. You can use the FARXIGA Savings Card to get Forxiga for as low as $0 per month if you are eligible.

France

Favorable opinion for reimbursement of FORXIGA (dapagliflozin) only in the treatment of adults with type 2 diabetes mellitus insufficiently controlled by metformin or a sulphonylurea as monotherapy, as an adjunct to diet and exercise, and in combination: 

• as dual therapy only with metformin or with a sulphonylurea, 
• as triple therapy only with metformin and a sulphonylurea or with metformin and insulin.

Unfavorable opinion for reimbursement of FORXIGA (dapagliflozin) as monotherapy and as dual therapy with insulin.  . 

Favorable opinion for reimbursement in the treatment of adult patients with chronic kidney disease, in addition to the standard of care therapy:

• with an estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73m² and a urine albumin to creatinine ratio (UACR) of between 200 and 5,000 mg/g,
• treated for at least 4 weeks with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB or sartan) at the maximum tolerated dose.

Unfavorable opinion for reimbursement in other adult chronic kidney disease populations. 

Favorable opinion for reimbursement as salvage therapy only, in addition to optimized standard of care therapy, in adults with chronic heart failure with reduced ejection fraction (LVEF ≤ 40%) who remain symptomatic (NYHA class II to IV) despite this treatment. The Committee considers that optimisation of treatment prior to the prescription of Forxiga (dapagliflozin) implies having used medicinal products in accordance with the recommended strategy and at the maximum tolerated dose, including ENTRESTO (sacubitril/valsartan) as a potential replacement for an ACE inhibitor or ARB, if their combination is compatible with the patient’s clinical profile. Unfavourable opinion for reimbursement in other populations in the “heart failure” indication, in particular as first-line treatment or in addition to non-optimised standard of care therapy including the valsartan/sacubitril combination (ENTRESTO).

Canada

Forxiga is reimbursed by the Canadian Agency for Drugs and Technologies in Health (CADTH) for the treatment of type 2 diabetes mellitus as an adjunct to diet and exercise, and for the treatment of heart failure with reduced ejection fraction. The CADTH has given Forxiga a positive recommendation for reimbursement based on its clinical effectiveness and cost-effectiveness compared to placebo or standard of care.

Italy

Forxiga falls under AIFA Class A drug list.  Forxiga was withdrawn from the market in Italy for the treatment of type 1 diabetes in 2020, following a review by the European Medicines Agency that concluded that the benefits of Forxiga did not outweigh its risks in this population. However, Forxiga is still authorized and reimbursed in Italy for the treatment of type 2 diabetes and chronic kidney disease in adults.

Germany

IQWiG has conducted several early benefit assessments of Forxiga for different indications over the years. The most recent one was published in March 2021, where IQWiG assessed Forxiga for the treatment of chronic kidney disease in adults with and without type 2 diabetes. IQWiG concluded that there was no proof of added benefit for Forxiga versus standard treatment for this indication.

United Kingdom

• In June 2023, NICE recommended Forxiga for treating chronic heart failure with preserved or mildly reduced ejection fraction in adults. This means that Forxiga is considered a cost-effective option for this condition and should be routinely available within the NHS. 

• In November 2020, NICE recommended Forxiga for treating chronic kidney disease in adults with and without type 2 diabetes. This means that Forxiga is considered a cost-effective option for this condition and should be routinely available within the NHS. 

• In August 2020, NICE recommended Forxiga for treating chronic heart failure with reduced ejection fraction in adults. This means that Forxiga is considered a cost-effective option for this condition and should be routinely available within the NHS. 

• In November 2016, NICE amended its previous guidance on Forxiga for treating type 2 diabetes in adults. This means that Forxiga can be used as part of dual or triple therapy with other oral antidiabetic medicines, depending on certain criteria such as blood glucose control, body weight, renal function and cardiovascular risk.

Conclusion

Known as Farxiga in the US and Forxiga in Europe and other countries is a medication belonging to the SGLT2 inhibitor class. It effectively treats type 2 diabetes, heart failure, and chronic kidney disease in adults. It works by inhibiting the SGLT2 protein in the kidneys, leading to increased excretion of glucose and sodium through urine. Forxiga’s benefits include improved blood sugar control, reduced risk of heart failure hospitalization, and slowed kidney disease progression. However, it also comes with potential side effects and varies in terms of approval, pricing, and reimbursement across different regions.

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