Dapagliflozin is a newer antidiabetic drug that belongs to the gliflozin class family. This class is also called SGLT2 inhibitors. Dapagliflozin has a lot of benefits. It not only controls your blood sugar level but also helps to reduce the progression of heart disease and kidney disease. In this post, we will talk about this potent antidiabetic drug and understand how dapagliflozin’s mechanism of action works in diabetes, heart disease and kidney disease. Dapagliflozin has a novel and unique mechanism of action. Mainly, typical antidiabetic drugs increase insulin secretion by working on the pancreas. On the contrary, this gliflozin drug is not dependent on the beta cells of the pancreas. Dapagliflozin directly works on the kidney and removes the excess glucose from your blood by the kidney via inhibiting the SGLT-2 transporter.

1. Everything you need to know about
Dapagliflozin mechanism of action
​
Introduction
Today, we will discuss a novel antidiabetic drug which has been popular for
a few years. Yes, I am talking about dapagliflozin. Here, you will learn about
dapagliflozin mechanism of action summary, uses, dosage,
contraindications, side effects, etc.
The prevalence of diabetes is being increased throughout the world. Our
researchers are continuously working on it and trying to find an innovative
therapeutic approach to control diabetes.
Dapagliflozin has been found during research. It has a unique mechanism
of action because it does not require the action of insulin.
It removes your elevated blood glucose through the kidney via urine.

2. Dapagliflozin has a lot of benefits. It not only controls your blood sugar level
but also helps to reduce the progression of heart disease and kidney
disease.
In this post, we will talk about this potent antidiabetic drug and understand
how dapagliflozin’s mechanism of action works in diabetes, heart disease
and kidney disease.
Let’s get started right away.
What is the use of dapagliflozin?
Dapagliflozin is a newer antidiabetic drug that belongs to the gliflozin class
family. This class is also called SGLT2 inhibitors.
The full form of SGLT2 inhibitors is sodium-glucose cotransporter-2
inhibitors.
There are two more drugs in this class, i.e. Empagliflozin and Canagliflozin.
Dapagliflozin was approved for medical use in 2014 by the US FDA with
the brand name Farxiga. It was developed by AstraZeneca.
It was marketed in European countries under the brand name Forxiga. The
current role of dapagliflozin in following indications –

3. Use of Dapagliflozin in T2DM
Dapagliflozin is the first novel SGLT2 inhibitor for the management of type 2
diabetes mellitus.
This drug is considered a second-line agent to treat T2DM. It may be given
as a first-line agent if metformin is contraindicated.
Dapagliflozin is used with diet, exercise and other antidiabetic drugs to
improve glycemic control.
Use of Dapagliflozin in Heart Disease
In July 2020, researchers found the effect of dapagliflozin in NYHA class II
to IV heart failure.
Here, NYHA is a New York Heart Association that represents the stages of
heart failure in classes.

4. According to a recent study in August 2023, it has been shown that
dapagliflozin significantly reduces all-cause mortality, death from
cardiovascular problems, and hospitalisation due to heart failure.
Therefore, dapagliflozin can be used as an off-label in heart failure patients
if the patient does not have diabetes mellitus. But this drug could be the
best choice if you have a heart failure with diabetes mellitus.
Use of Dapagliflozin in kidney disease
In April 2023, the effect of dapagliflozin was found to improve kidney
outcomes in kidney disease.
A study published in Kidney International Reports in 2022 stated that
dapagliflozin reduces the risk of end-stage renal disease in patients with
chronic kidney disease, whether diabetic or non-diabetic.
How does dapagliflozin work in the body?
Dapagliflozin has a novel and unique mechanism of action.
Mainly, typical antidiabetic drugs increase insulin secretion by working on
the pancreas.
On the contrary, this gliflozin drug is not dependent on the beta cells of the
pancreas. Dapagliflozin directly works on the kidney and removes the
excess glucose from your blood by the kidney via inhibiting the SGLT-2
transporter.
Let’s understand this dapagliflozin mechanism of action summary in detail
with basic concept –

5. Physiology & function of SGLT-2 transporter
Usually, SGLT-2 is a transporter or pump that is present in your PCT
(Proximal Convoluted Tubules) of the kidney’s nephron.
SGLT-2 stands for sodium-glucose transport protein. The primary function
of this transporter is to reabsorb (or reuptake) sodium and glucose into your
blood.
Three main steps are involved in urine formation: filtration, reabsorption,
and secretion.
Your body filters your glucose in the nephron. Then, it reabsorbs 90% of
glucose into your blood by a sodium-glucose pump and excretes the rest of
the content.
Dapagliflozin mechanism of action in T2DM

6. In diabetes, having excessive glucose is not good.
We already have a lot of antidiabetic drugs that need the action of insulin.
However, researchers wanted to do something beyond insulin, where
insulin is not required.
Therefore, scientists have made an incredible molecule that is
dapagliflozin.
Dapagliflozin works on the kidney. The specialty of this molecule is that it
restricts the re-entry of glucose into your blood.
This drug stops the glucose reabsorption step in urine formation by
inhibiting SGLT-2 (sodium-glucose transport protein-2).
This way, the dapagliflozin drug decreases your blood glucose level by
excreting the glucose content via urine.
That’s why dapagliflozin is called SGLT2 inhibitor.

7. Dapagliflozin mechanism of action in heart failure
Dapagliflozin works as an osmotic diuretic. Due to this osmotic diuretic
mechanism, dapagliflozin protects the cardiovascular and helps in cardiac
remodelling.
If you have heart failure, dapagliflozin helps decrease the workload on your
heart.
This drug excretes sodium from your blood and creates a hyponatremic
effect. Due to this effect, it decreases the preload and after-load effect on
the heart. It also improves the ejection fraction of your heart.
Once you start taking this drug. You will begin to feel improvement in the
symptoms of heart failure, such as breathlessness, tiredness and swelling
in your lower legs.
Many studies suggest SGLT2 inhibitors have cardiovascular benefits, such
as –
● A study published in Journal of Endocrinology, Metabolism and
Diabetes of South Africa 2023 shows the cardiorenal benefits of
SGLT2 inhibitors like empagliflozin, canagliflozin, and dapagliflozin.
● A review and meta-analysis study published in ESC Heart Failure
2020 also revealed the benefit of an SGLT2 inhibitor in heart failure.
● According to a study of the current cardiology report, 2018, SGLT2
inhibitors help decrease your blood pressure and cardiovascular risk.

8. Dapagliflozin mechanism of action in CKD
CKD stands for chronic kidney disease, where a person starts losing
nephron cells, which stops the kidney’s function over time.
It could be due to glomerulonephritis, type 2 diabetes, hypertension or
cardiovascular disease.
Taking dapagliflozin block SGLT-2 protein helps to reduce inflammation and
pressure in the kidneys. It protects against progressive kidney damage.
Dapagliflozin decreases the intraglomerular pressure by natriuresis effect
(excretion of sodium in the urine), which further helps to reduce
albuminuria.
It also decreases inflammatory mediators, such as interleukin-6, nuclear
factor-kB, and profibrotic factors.
Dapagliflozin also acts as a nephroprotective drug with or without diabetes.
dapagliflozin mechanism of action pdf
What are the most common side effects of dapagliflozin?
In addition to its therapeutic effects, dapagliflozin may produce some
unwanted effects as well.
1. Frequent UTI (Urinary tract infection)
The diuresis effect of dapagliflozin may cause bacterial or fungal infections
like genital mycotic infections –
● Vulvovaginal candidiasis (vaginal fungal infection)
● Balanitis (pain, inflammation, and irritation in the penis)

9. So, you should maintain personal hygiene, especially in genital areas.
2. Dehydration
You may have dehydration due to glucosuria/glycosuria and the osmotic
diuresis effect of gliflozin. You need to take a sufficient amount of water to
avoid dehydration.
3. Hypotension
The natriuresis effect (loss of sodium in the urine) of dapagliflozin may
decrease your blood pressure level and cause a hypotensive effect.
So, it is also a helpful drug if you have hypertension with type 2 diabetes.
But you need to reduce the dose of your existing antihypertensive
medications like ACE inhibitors, diuretics or others.
4. Weight loss
You will observe slight weight reduction during gliflozin therapy because
you will be losing calories (or glucose) by the glucosuria effect. However, it
may be beneficial for obese patients.
5. Hypoglycemia
Dapagliflozin may cause mild hypoglycemia if it is used in combination with
insulin injection or sulphonylurea-like drugs.
It would help if you reduce the dose of insulin or other oral hypoglycaemic
agents while taking SGLT2 inhibitor drugs.

10. 6. Polyuria and polydipsia
You may have an excessive thirst and frequent urination due to the osmotic
diuretic effect of dapagliflozin.
7. Risk of bladder cancer
As we know, urinary tract infection (UTI) is dapagliflozin’s most common
side effect. This UTI may further contribute to bladder cancer.
When not to use dapagliflozin?
Dapagliflozin is contraindicated in certain conditions –
1. Pregnancy and breastfeeding
Dapagliflozin comes in category C medications.
Currently, no data are available on the use of dapagliflozin in pregnant
women. The researcher found reproductive toxicity in animals during
dapagliflozin, especially in 2nd and 3rd trimesters.
It was also found that dapagliflozin can be secreted in milk while
breastfeeding.
Therefore, it would be best to avoid dapagliflozin in pregnancy and
lactation. We already have insulin injections and metformin tablets as a
safer option.

11. 2. Severe kidney disease (GFR<30ml/min)
Dapagliflozin drug should not be used for severe kidney damage,
especially in stages 4 and 5 of CKD.
At these stages, the GFR (Glomerular Filtration Rate) value decreases
below 30 ml/min.
This drug is not recommended in GFR 30 to 40 ml/min. You should strictly
avoid dapagliflozin if someone has a GFR value of less than 30 ml/min.
3. History of bladder cancer
You need to avoid dapagliflozin if a patient has active bladder cancer or a
history of bladder cancer.
4. History of ketoacidosis
You should avoid this drug if you have had ketoacidosis in the past
because SGLT-2 inhibitors themselves cause ketoacidosis.
In Feb 2022, a study reviewed the dapagliflozin is associated with diabetic
ketoacidosis.
In this condition, your body starts to produce ketone bodies. Due to this,
your blood becomes acidic (pH below 7).
In ketoacidosis, you may feel burning while urinating, blood in urine, pain in
the lower abdomen, and shortness of breath. If you observe these
symptoms, you should stop this medicine immediately and contact your
doctor.
5. Allergic reaction

12. You should immediately discontinue this medicine if you feel a
hypersensitive reaction to this dapagliflozin.
How and when to take dapagliflozin?
Dapagliflozin causes polyuria due to its osmotic diuretic effect. So, taking
one tablet in the morning with or without a meal is always better.
The dose of dapagliflozin depends on the severity of the disease and type
of disease, such as –
Dapagliflozin dose for type 2 diabetes mellitus
Dapagliflozin is considered a first-line agent if metformin is contraindicated.
You may be prescribed this medicine at the disease’s initial or late stage. It
can be used as a monotherapy or added to insulin/another oral
hypoglycemic agent.
The starting dose of dapagliflozin in T2DM is 5 mg, administered once
daily. It can be increased up to 10 mg if clinically indicated.
The maximum dapagliflozin dose per day is 10 mg.
Dapagliflozin dose for heart disease
The recommended dose of dapagliflozin is 10 mg once daily dosing in
NYHA class II–IV heart disease.
Dapagliflozin dose for chronic kidney disease

13. The usual dose of dapagliflozin is 10 mg once daily in chronic kidney
disease.
Taking dapagliflozin increases serum creatinine and reduces eGFR. These
changes may be more prevalent in elderly patients and patients with
impaired renal function.
So, it would help if you kept in mind GFR values. The normal eGFR value
is 90 ml/min or more.
No dose
adjustment
Not
recommended
Contraindicated
eGFR values
(ml/min/1.73m2)
45 or above 30 or less than
45
Less than 30
What dapagliflozin brands are popular in India?
Dapagliflozin is prominent in India with brand names of –
● Forxiga 5 mg or 10 mg tablet
● Oxra 5 mg or 10 mg tablet
● Dapaone 5 mg or 10 mg tablet
● Sugaflo 5 mg or 10 mg tablet

14. Dapagliflozin is also available in combination with traditional antidiabetic
drugs like –
1. Dapagliflozin and metformin combination
You can get this fixed dose combination of Dapagliflozin & Metformin HCL
extended-release tablets with brand names of –
● Gledepa met XR 10/500mg or 1000 mg
● Glucreta M 5/500 or 10/1000
● Dapaturn M 5 or 10 mg tablet ER

15. ● Dapanorm M 5/500 mg
2. Dapagliflozin and vildagliptin combination
The FDC of dapagliflozin & vildagliptin sustain release tablet is available
with brand names of –
● Jalra-DP 10mg/100mg
● Daparyl V 10mg/100mg
● Torglip D 10mg/100mg
● Zukanorm D 10mg/100mg
3. Dapagliflozin + vildagliptin + metformin combination
This triple FDC combination (Dapagliflozin + vildagliptin + metformin) is
available with brand names of –
● Daparyl VM 10mg/500mg/100mg Tablet
● Zomelis-DM Forte Tablet SR
● Jalra Trio Tablet
● Vylda-DM 100/10/1000 Tablet SR
What are the clinical benefits of dapagliflozin?

16. Dapagliflozin does not only improve your glycaemic control, but it also has
many benefits like –
● Effective in heart failure (NYHA class II-IV)
● Effective in chronic kidney disease if GFR is 45 mg/ml or above
● Rarely cause hypoglycaemia
● Helps to reduce blood pressure
● Helps in weight reduction
● Reduce fatty liver content, especially NAFLD
Conclusion
Dapagliflozin is a potent, well tolerated and safest antidiabetic drug.
In this post, we understood the dapagliflozin mechanism of action and how
it works in diabetes.
Besides its use in diabetes, dapagliflozin has a cardio-renal effect.
This medicine can be considered a rising star in treating diabetes patients.
This was all about the dapagliflozin mechanism of action summary, uses,
benefits, side effects, and contraindications.
Please share this post on social media if you found it informative.
FAQ

17. Q1. Is dapagliflozin bad for the kidneys?
Dapagliflozin would be the right choice for kidney disease, whose GFR
value is more than 45 ml/min. It can be contraindicated if GFR is less than
30 ml/min.
Q2. Does dapagliflozin increase creatinine?
Dapagliflozin drug increases serum creatinine levels and reduces eGFR.
You should avoid this medicine if you have a higher creatinine level or
lower GFR value.
Q3. How long does dapagliflozin take to work?
The onset of action of dapagliflozin is 2 hours. Your blood glucose levels
will drop after about two hours of taking dapagliflozin. However, it may take
up to a week to become fully effective.
Q4. Which is better, metformin or dapagliflozin?
Metformin is a first-line antidiabetic drug. Suppose metformin is
contraindicated or ineffective. In that case, dapagliflozin may be a
second-line option for the treatment of diabetes.
Q5. What is a substitute for dapagliflozin?
If dapagliflozin is contraindicated or not tolerated. Then, you may go to
other drugs of this class, such as Canagliflozin or Empagliflozin.
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