What are SGLT2 inhibitors drug? Everything you need to know

Posted On December 23, 2021May 28, 2022

Introduction 

What are SGLT2 inhibitors? You must have heard some medicine brand names like Jardiance, Forxiga, or Invokana.

These brands are emerging and trending nowadays. Here, I will review these novel anti-diabetic drugs, known as SGLT2 inhibitors (or Gliflozins).

Diabetes is a relatively common medical condition because the incidence is very high in China, India, and other countries. Till now (as of 2021), around 540 million people have been suffering from diabetes worldwide.

If you have diabetes or someone in your home dealing with diabetes and your blood glucose level is not controlling well to usual anti-diabetic medicines. In that condition, SGLT2 inhibitor medicines are a perfect choice. 

Although, these medicines are costly. But they are very strong and potent anti-diabetic drugs. If your diabetes is not managed adequately, you can take this medicine under medical supervision.

Before taking this drug, you must know everything about your medicine. Here, I have made a complete guide on SGLT2 inhibitors. You will know –

What are SGLT2 inhibitors?

How do they work?

Who should not take SGLT2 inhibitors?

Are SGLT2 inhibitors safe?

I’ll help you answer all these questions in this post. So, let’s get started right away.

What are SGLT2 inhibitors? 

SGLT2 inhibitors are a newer oral hypoglycemic agent used in Type 2 diabetes mellitus (T2DM) conditions. These are prescription medicines, also known as “Gliflozins.”

SGLT2 inhibitors are powerful anti-diabetic drugs. These drugs are generally recommended to those patients who are not responding to traditional anti-diabetic drugs like Metformin, Sulphonylureas, Voglibose, etc. 

It is also considered for those patients who are not willing to start insulin injection. 

So, they are used as second- or third-line anti-diabetic treatment options. 

What does SGLT2 inhibitor stand for?

The full form of SGLT2 inhibitors is sodium-glucose cotransporter-2 inhibitors. These drugs lower your blood glucose level by interfering in the sodium and glucose pumps of the kidney. 

What are examples of SGLT2 inhibitors?

Currently, there are three most prominent SGLT2 inhibitors available in the international market. These SGLT2 inhibitors examples are Dapagliflozin, Canagliflozin, and Empagliflozin. They are well approved by US-FDA.

Canagliflozin was the first molecule of the Gliflozins family approved by US-FDA in 2013. After that, Dapagliflozin and empagliflozin were approved in 2014. 

A Japanese pharmaceutical company (Kissei Pharmaceutical) discovered a new gliflozin molecule – Remogliflozin. In May 2019, Glenmark first launched this drug in the Indian market. 

Ertugliflozin is another gliflozin drug approved in European countries in March 2018. This drug was got approval in the US market in December 2019. 

Ipragliflozin and Luseogliflozin were approved for medical purposes in Japan in 2014. 

Some gliflozins drugs are going under clinical trials like Sergliflozin, Sotagliflozin, and Tofogliflozin.

What are the brand names for SGLT2 inhibitors?

There are specific popular brand names of SGLT2 inhibitors available in the market. These are – 

• Canagliflozin – Invokana (Johnson and Johnson ltd.), Sulisent, Motivyst, Prominad 

• Dapagliflozin – Forxiga (Astrazeneca), Glucreta, Gluflozin 

• Empagliflozin – Jardiance (Boehringer Ingelheim), Gibtulio 

Gliflozins are also available in combination with traditional anti-diabetic drugs like – 

1. Empagliflozin with metformin

• Jardiance Met (Boehringer Ingelheim)
• Gibtulio Met (Lupin ltd.)

2. Empagliflozin with Linagliptin 

• Glyxambi (Boehringer Ingelheim)
• Ajaduo (Lupin ltd.) 

3. Canagliflozin with metformin 

Vokanamet tablet (Johnson and Johnson ltd.)

4. Dapagliflozin with metformin 

Gledepa met XR (Abbott), Glucreta M (Torrent), Dapaturn M (Lupin), Dapaease M (Jubiliant), Dapaglyn M (Zydus), Dapanorm M (Alkem)

How do SGLT2 inhibitors work?

SGLT2 inhibitors have a novel and unique mechanism of action. 

Mostly, typical anti-diabetic drugs increase insulin secretion by working on the pancreas. 

While SGLT2 inhibitors (gliflozins) are not dependent on beta cells of the pancreas. They directly work on the kidney and remove the excess glucose from your blood by your kidney. 

Let’s understand through basic concept – how do gliflozins exactly work?

Normally, sodium-glucose transporter-2/pump is present in your PCT (Proximal Convoluted Tubules) of the kidney’s nephron. The primary function of this sodium-glucose pump is to reabsorb (or reuptake) sodium and glucose into your blood.

There are three main steps involved in urine formation: filtration, reabsorption, and secretion. 

Your body filters your glucose in the nephron. Then it reabsorbs 90% glucose into your blood by sodium-glucose pump, and the rest of the stuff excrete out. 

In diabetes, getting excessive glucose in your blood is not good. 

Therefore, scientist has made an incredible molecule – gliflozins. The specialty of this molecule is that it restricts the re-entry of glucose into your blood. 

These drugs stop the glucose reabsorption step in urine formation by inhibiting sodium-glucose cotransporter-2. 

That’s why these drugs are called SGLT2 (Sodium-Glucose Cotransporter-2) inhibitors. 

These gliflozin drugs decrease your blood glucose level by excreting the glucose content via urine. 

What are SGLT2 inhibitors side effects?

As I discussed the mechanism of SGLT2 inhibitors, these drugs excrete out the glucose through urine that causes the glucosuria effect (presence of sugar in urine). 

By this mechanism, these drugs may cause some side effects like – 

1. Frequent UTI (Urinary tract infection)

You may have bacterial or fungal infections like genital mycotic infections –

• Vulvovaginal candidiasis (vaginal fungal infection) 
• Balanitis (pain, inflammation, and irritation in the penis)

So, you should maintain personal hygiene, especially in genital areas. 

2. Dehydration and hypotension

The glucosuria effect of gliflozins may cause dehydration and hyponatremia (loss of sodium ions). You need to take a sufficient amount of water to avoid dehydration. 

These drugs may also decrease your blood pressure level and produce a hypotensive effect by this mechanism. 

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 drugs like ACE inhibitors, diuretics, or others.

3. Weight loss

You will observe slight weight reduction during gliflozins therapy due to losing calories (or glucose). However, it may be beneficial for obese patients. 

4. Hypoglycemia 

Gliflozins may cause hypoglycemia if used in combination with insulin or sulphonylurea-like drugs. 

You need to reduce the dose of insulin or other oral hypoglycaemic agents while taking gliflozin drugs.
 

5. Excessive thirst and frequent urination

Due to its osmotic diuresis action, it will increase the frequency of urine and thirst. 

6. Risk of foot amputations

As per FDA (Food and drug administration), the Canagliflozin drug may have an increased risk of leg and foot amputations, especially in toes. If you are feeling pain, sensitivity, or infections near the feet region. Then you must consult your doctor. 

7. Risk of bone fracture 

Canagliflozin is also associated with an increased risk of bone fracture. As per the US-FDA report, canagliflozin may decrease bone mineral density. 

What are the benefits of SGLT2 inhibitors?

SGLT2 inhibitors do not only improve your glycaemic control, but these drugs also have many benefits like – 

1. SGLT2 inhibitors in heart failure, hypertension, and kidney 

As we have seen, Gliflozin drugs work as a diuretic. Due to this mechanism, these drugs provide you cardiorenal protection. 

Even many studies suggest SGLT2 inhibitors have cardiovascular benefits. 

A recent study published in the journal Diseases 2020 shows the cardiorenal benefits after using Gliflozins like empagliflozin, canagliflozin, and Dapagliflozin. 

Another recent review and meta-analysis study published in ESC heart failure 2020 also revealed the benefit of an SGLT2 inhibitor in heart failure. In this study, Gliflozins drugs significantly reduced the risk of cardiovascular mortality. 

According to a study of the current cardiology report, 2018 Gliflozins help decrease your blood pressure and cardiovascular risk. As per this study, these drugs also help slow the progression of kidney disease. 

These medicines will provide you good benefits if you have hypertension and heart disease problems (like ischemic heart disease) with type 2 diabetes mellitus. 

2. SGLT2 inhibitors in HbA1C and weight reduction

A 2015 study found that Gliflozin drugs significantly reductions in HbA1C. In this study, Canagliflozin was found (HbA1c reduction 1.01%) highly effective drug among all SGLT2 inhibitors. 

This study also suggests that gliflozins are better drugs for weight reduction. 

So, these drugs effectively reduce blood sugar levels and weight control without producing severe adverse reactions like hypoglycemia. 

3. SGLT2 inhibitors in liver disease

A study published in Diabetes and Metabolism 2019 was found a positive effect of SGLT2 inhibitors in liver disease. 

These drugs are potential to reduce fatty liver content and improve biological markers like liver enzymes, increased high-density lipoprotein, and decreased triglycerides. 

Gliflozins are mainly effective in NAFLD (Non-alcoholic fatty liver disease). 

So, you may take this drug if you have a fatty liver disease with type 2 diabetes. 

Who should not take SGLT2 inhibitors?

You should avoid SGLT2 inhibitors drug in certain conditions – 

1. Pregnancy and breastfeeding 

SGLT2 inhibitors are category C medications. According to the American College of cardiology 2021, SGLT2 inhibitors are unsafe in pregnancy and lactating mothers. 

Some data suggest reproductive toxicity in animals during SGLT2 inhibitors. 

2. Severe kidney disease 

Gliflozin drugs should not be used in certain GFR values – 

Dapagliflozin < 45 ml/min

Empagliflozin < 45 ml/min

Canagliflozin < 30 ml/min

3. Ketoacidosis history

You should avoid these drugs if you have had ketoacidosis in the past because SGLT-2 inhibitors themselves cause ketoacidosis. 

In April 2015 FDA issued a warning that Gliflozins may increase the risk of developing 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. 

When should I take SGLT2?

Since Gliflozins have osmotic diuresis action. So, it is always better to take one tablet in the morning with or without a meal.

SGLT2 inhibitors comparison chart

Conclusion 

So, we have seen – what are SGLT2 inhibitors and how do they work. 

SGLT2 inhibitor drugs are an attractive and effective treatment option for type-2 diabetes mellitus patients. They have good tolerability and safety profile. 

Apart from lowering your blood glucose level, these drugs are helpful in heart failure, liver disease, weight reduction, and kidney protection.

In future, we can consider them rising stars in the treatment of diabetes patients. 

Although these are the latest drugs and we don’t have sufficient data regarding side effects. 

I urge you (patients) and healthcare professionals to report newer side effects of Gliflozins at your nearest AMC (ADR Monitoring Center).

If you have any queries regarding this post – what are SGLT2 inhibitors. Let me know in the comments below. I will try my best to answer all of them.

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FAQ

Q1. What drugs are SGLT2 inhibitors?

Ans. Those drugs which are ending with gliflozin are called SGLT2 inhibitors. For example, Canagliflozin, empagliflozin, and Dapagliflozin. 

Q2. Is metformin an SGLT2 inhibitor drug?

Ans. Metformin belongs to the biguanides class of anti-diabetic drugs. Metformin is also available in FDC (fixed-dose combination) with SGLT2 inhibitors like Jardiance Met (Empagliflozin+Metformin), Vokanamet (Canagliflozin+metformin), Dapaglyn M (Dapagliflozin+Metformin).

Q3. Can SGLT2 inhibitors cause hypoglycemia?

Ans.SGLT2 inhibitors significantly reduce your blood glucose level without causing hypoglycemia.