Which SGLT2i is best for CKD?

Which SGLT2i is best for CKD?

There is not a best one. They all have a major beneficial effect for most patients with CKD. Let;s start with some background.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors (or SGLT2is or ‘gliflozins’) are commonly used to treat type 2 diabetes (DM2). You may be prescribed it to take one its own, or with other diabetes medication.

There are a few different tablets in the SGLT2 inhibitor group, these include:

• Dapagliflozin – 10 mg once a day
• Canagliflozin – 100-300 mg
• Empagliflozin – 10-25 mg.

Chemical structure of SGLT2is

What else are SGLT2 inhibitors used for?

As well as DM2, they are also a very effective treatment for:

• Chronic heart failure (CHF)
• Chronic kidney disease (CKD) when there is proteinuria (protein in urine); when the GFR is 60-25 ml/min, and the uACR is >25 mg/mmol. This is often due to glomerular diseases like  diabetic nephropathy (diabetes affecting the kidneys). Thus SGLT2is may slow the progression of chronic kidney disease in such patients.

Here is more information on the use of SGLT2is in CKD.

How do SGLT2 inhibitors work?

SGLT2 inhibitors work by blocking the action of the SGLT2 transporter (protein) in the distal convoluted tubule (DCT) of the kidneys. This protein is responsible for reabsorbing glucose back into the bloodstream from the urine. By inhibiting SGLT2, these drugs increase the amount of glucose lost in the urine, leading to lower blood glucose levels.

One of the ‘good’ side effects of SGLT2 inhibitors is weight loss. Why? As you are losing glucose from your body, you are effectively losing calories, which can be beneficial.

In the long-term, good control of blood glucose levels reduces the risk of developing problems with your eyes, kidneys and feet.

They also increase the amount of sodium and water lost in the urine. This may explain why they have a useful ‘side-effect’ of reducing blood pressure.

They have also been shown to lower the risk of heart attacks, help people with heart failure and slow the progression of kidney disease. This may in part be due to their effect on blood pressure. This class of medication may be beneficial if you already have these conditions or are at high risk of developing these in the future.

How are SGLT2 inhibitors taken?

SGLT2 inhibitors are given in a tablet form.

Because of the way that SGLT2 inhibitors work, your urine will test positive for glucose while you are on this medication.

What other side effects do SGLT2 inhibitors cause?

Most people can take SGLT2 inhibitors without any side effects. However, like all medications, SGLT2 inhibitors can cause side effects in some people – and, very rarely, these can be serious.

Some of the more common side effects include:

• Dehydration. You may find you make more urine when you take these drugs. This can sometimes lead to dehydration. This is more likely for people also taking water tablets (diuretics) such as Bendroflumethiazide, Furosemide, Bumetanide or Metolazone
• Low blood sugar (hypoglycaemia). This is more likely to happen in people with diabetes that are already taking other diabetes medication. When you start an SGLT2 inhibitor, a change in your diabetes medication might be needed
• Urine and fungal infections. You may get urine and fungal infections. This includes thrush around the vagina or penis. These should be reported to your doctor are usually treatable. Maintaining good hygiene of the genital area should reduce your risk.

Far less common, but important, side effects of SGLT2 inhibitors include:

• Diabetic ketoacidosis. SGLT2 inhibitors can raise the blood levels of chemicals called ketones. Very rarely, this can lead to a condition called ‘diabetic ketoacidosis (DKA)’, which is more usually seen in people with type 1 diabetes but can occur in people with type 2 diabetes.
  Note. Contact your doctor or nurse straight away if you notice a sweet smell on your breath, sweat or urine (like nail varnish remover); or if you have symptoms such as: feeling sick, tummy pain, losing weight quickly, feeling very thirsty, breathing unusually quickly, confusion, tiredness or sleepiness
• Peripheral vascular disease (PVD). There may be a small risk of worsening foot ulcers, gangrene or severe foot infections, which may lead to an amputation – particularly among people with diabetes or who have or have had foot disease
• Fournier’s gangrene. This is a severe deep skin infection that often causes pain, swelling and/or redness around the genital area. This usually starts with an area of redness or a sore in the genital/groin area that spreads quickly. People also usually feel very unwell. 

Note. If you suspect you may have one of these important side effects, immediately stop the SGLT2 inhibitor and seek urgent medical attention.

Sick day rules

You should stop taking SGLT2 inhibitors if you become very unwell, especially if you think you have a significant infection, or have vomiting and/or diarrhoea, or are not eating and drinking. These are called sick day rules. You can start taking them again once you are back to normal health. You should inform your doctor or nurse at the earliest opportunity that you have stopped your SGLT2 medication.

How SGLT2 inhibitors affect blood sugar

On their own they will not cause your blood glucose level to go too low (i.e. cause hypoglycaemia, which is classed as a blood glucose level less than 4 mmol/L) but they may increase the risk of this happening if you also take insulin or drugs called sulphonylureas (e.g. gliclazide).

This also means that if you do not have diabetes, and you are taking them for heart failure of CKD, they will not drop your blood sugar.

Who should not take SGLT2 inhibitors?

SGLT2 inhibitors are usually prescribed to adults who have type 2 diabetes, heart failure or CKD. But they are not suitable for some people. You should tell your doctor before starting any of this medication if you:

• Have advanced CKD (GFR <25 ml/min)
• Are pregnant, planning a pregnancy or breastfeeding
• Have problems with repeated urine infections
• Liver problems
• Type 1 diabetes
• Any history of diabetic ketoacidosis.

Note. They should not be prescribed for patients with type 1 diabetes, or have had an episode of DKA.

Summary

We have described which SGLT2i is best for CKD. There is not a best one. They all have a major beneficial effect for most patients with CKD. We hope it has been helpful.

Other resource

This is a useful patient information leaflet on SGLT2 inhibitors and CKD. And this is some more useful information from the NHS.

Last Reviewed on 19 April 2024