SGLT2 Inhibitors Side Effects - Mechanism of Action
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Drug Side Effects

Side Effects Of SGLT2 Inhibitors

Nov 24, 2016

Glucose is the fuel of the human body using which we generate energy. This energy is then used for all the life processes that happen inside our bodies. Apart from getting glucose from the digestion of food, our bodies have developed an elaborate system of re-absorbing excess glucose that is being removed by the kidneys. SGLT2 is a protein whose job is to facilitate glucose reabsorption in the kidney. It is highly efficient and is responsible for 90% of glucose reabsorption.

Now, since diabetics already have an excess of glucose in their bodies, it does not really make sense to re-absorb excess glucose that the kidneys have worked so hard to remove. And thus to negate the activity of SGLT2, a new class of drugs, called SGLT2 inhibitors, is used to manage blood sugar levels in diabetics.

SGLT2 inhibitors (Sodium-Glucose Linked Transporter) are chemicals that prevent re-absorption of glucose by the kidneys, so that it spills out into the urine. This prevents sugar build-up in the bloodstream and brings down blood glucose and insulin levels.

SGLT2 inhibitors Mechanism of Action

SGLT2 inhibitors are a new class of drugs for the treatment of type 2 diabetes. They lower blood sugar concentrations by increasing renal excretion of glucose. These compounds reduce glucose reabsorption in the kidney and lower blood glucose independent of changes in insulin concentrations.

How Should This Medicine be Used?

SGLT2 inhibitors (Empagliflozin) are available as a tablet to be taken orally. It is usually taken once a day in the morning with or without food. Consume SGLT2 inhibitor (empagliflozin) at around the same time every day. Follow the directions written in your prescription label carefully, and ask your healthcare practitioner or pharmacist to explain any part you do not understand. Take SGLT2 inhibitor (empagliflozin) exactly as directed. Do not take more or less of it or take it more often than prescribed by your healthcare practitioner.
Your healthcare practitioner may start you on a low dose of the medication and depending on how you respond to it, may increase your dose gradually.

This medication simply helps you in controlling your blood sugar levels; it cannot actually treat your diabetes. Do not stop taking your medication just because you are feeling well and never stop taking any medication without consulting your healthcare practitioner.

Most Prescribed Names In This Category of Drugs Include

Canagliflozin (Invokana), Dapagliflozin (Forxiga), Empagliflozin (Jardiance)

Side Effects That Could Happen as Soon as You Start Taking the Medication

Following are some common SGLT2 inhibitors side effects:

Urinary Tract Issues

Side-effects of SGLT 2

Side-effects of SGLT 2

These drugs speed up the excretion of sugar by way of urine. Since bacteria and yeast love sugar, this makes people taking this drug highly susceptible to urinary tract infections. These drugs may also make you urinate more frequently.

Low Blood Sugar or Hypoglycemia

These drugs act by increasing the excretion of glucose through urine. This mechanism of action may cause excess excretion of glucose from the body, leading to dangerously low blood sugar levels. Excess sweating, palpitations, dizziness, extreme hunger, palor and tiredness are symptoms that can occur due to hypoglycemia. Long-term effects of SGLT2 inhibitors have not been studied yet, however hypoglycemia is one of the well-documented SGLT2 inhibitors side effects.

Other Symptoms

Individual drugs have been found to have a higher incidence of bladder cancer (dapagliflozin) and increase in HDL and LDL cholesterol (canagliflozin). This has been observed in clinical trials. In rare cases, the drug has also been known to cause diabetic ketoacidosis.

What Can You Do?

These adverse effects can often be handled by your doctor by switching you over to some other class of diabetic medications in case you are prone to urinary infections or have any kind of compromised kidney function. Dietary supplements can help support blood sugar control, so they can help you reduce the burden of medications and their side effects.

Should You Be Using SGLT2 inhibitors for a Long Term?

While SGLT2 inhibitors have not been studied for the nutrients that they deplete with long-term use, clinical trials of dapagliflozin showed some incidence of liver damage and breast and bladder cancers amongst users. Trials with canagliflozin showed increases in both LDL (bad) and HDL (good) cholesterol.

What Special Precautions Should I Follow?

You need to inform your healthcare practitioner if you are allergic to the active compound of the medicine or any substances in it. You also need to tell your healthcare practitioner about any other prescription and non-prescription drugs you are taking or any supplements or herbal products you might be taking.

If you have a kidney problem, be sure to tell your healthcare practitioner; it is likely that he/she may not put you on this medicine. Also talk to your healthcare practitioner if you are pregnant or plan to get pregnant. Do not breastfeed while on this drug.

What Should I Do if I Forget a Dose?

Take it as soon as you remember. If more than 12 hours have passed since your missed dose, then skip the missed dose and take the next dose at the regularly prescribed time. Do not double your dose to compensate the missed one.

What Should I Know About Storage and Disposal of this Medication?

Store SGLT2 inhibitors (empagliflozin) at room temperature 68-77°F (20-25°C).

Dietary Considerations, While Taking Medicine: Follow all exercise and dietary recommendations made by your healthcare practitioner or dietitian. It is important to eat a healthy diet, regulate your lifestyle and follow a regular exercise regimen. Drink enough fluids throughout the day while you are on this medication.

Drug Interactions

Insulin or Insulin Secretagogues

Taking SGLT2 inhibitors along with insulin or drugs called insulin secretagogues increases the risk of hypoglycemia.

Positive Urine Glucose Test

Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors, as SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. Use alternative methods to monitor glycemic control.

What are the ingredients in Jardiance (empagliflozin)?

  • The active substance is empagliflozin. Each tablet contains 10 mg or 25 mg empagliflozin.
  • The other ingredients are:

Tablet core: lactose monohydrate, cellulose microcrystalline, hydroxy propylcellulose, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate

Film coating: hypromellose, titanium dioxide, talc, macrogol, iron oxide yellow

Parting Thoughts

Being diagnosed with diabetes is not the end of the world. Type 2 diabetes is a dietary disorder and it follows that a holistic diet and a healthy lifestyle are vital for reversing this condition. Diabetes can be tough, but you can manage to live well with it by following some simple rules. You can succeed with diabetes through knowledge, good medical care, exercise, proper diet and emotional strength.

Staying strong emotionally throughout the journey of your diabetes treatment is key to keeping stress and your blood glucose levels low.

Dietary supplements that have been studied to help with controlling blood sugar could assist you in reducing the burden of your prescription drugs.

There has been lot of research in areas where diet and lifestyle changes, like intermittent fasting, yoga, meditation, weight loss and moderate exercise, were shown to have a huge positive impact on diabetes. You should explore all of these avenues, to get the best results for yourself.

Nachiket Rajadhyaksha
Nachiket holds a first class degree in Pharmacy and is passionate about writing. He believes that subject experts must simplify medical concepts to make them interesting and accessible to everyone.


1. Dailymed, U.S.National Library of medicine
2. Medline Plus, U.S. National Library of medicine
3. Useful information on Canagliflozin by Canadian Diabetes Association
4. Medline Plus, U.S.National Library of medicine
5. Useful information on Canagliflozin by Canadian Diabetes Association
6. Patient information leaflet Jardiance (empagliflozin)
7. Medline Plus, U.S. National Library of medicine
8. Prescribing information – Jardiance
9. Package leaflet: Information for the patient
10. Package leaflet: Information for the patient