SGLT2-inhibitors: a new era in protecting kidney health?
A type of medication called SGLT2 inhibitors could help people with chronic kidney disease (CKD) stay well for longer. We spoke to our funded researcher, consultant nephrologist Dr Dominic Taylor from the University of Bristol to hear more about SGLT2 inhibitors and his study into getting access to this new treatment.
To start off, could you explain what SLT2 inhibitors are?
SGLT2 inhibitors, often called “SGLT2i’s”, are given as tablets; usually once a day. They have a brand name and a chemical (generic) name which ends ‘–flozin’.
These drugs alter the way the kidneys handle salt and sugar, and can help the body get rid of more sugar in the urine. Because of this, SGLT2i’s can treat people with diabetes, and recent research has shown they can benefit heart failure and CKD patients too. We know SGLT2i’s can reduce the amount of protein lost in the urine in CKD, how quickly kidney function is lost, and reduce the risk of death from heart failure.
How do SGLT2i’s protect kidney function and what hope do they offer?
Although we do not have a cure, the future looks brighter with multiple treatment options for kidney disease. For many patients, SGLT2i’s can offer more protection on top of medications such as angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) which have been the standard approach to care in kidney disease patients. ACE inhibitors and ARBs reduce the strain on the delicate kidney filters by decreasing blood pressure and reduce how much protein is lost in the urine.
SGLT2i’s also protect the kidney, but in a different way. By increasing the amount of sugar and salt in the urine they can reduce pressure in the kidney filters and improve their function. Because these treatments work in different ways we can combine them for a greater overall effect. A key challenge for healthcare providers is getting the use of these treatments right, so all patients receive the full benefit.
Medication guidelines
The SGLT2i-s empagliflozin and dapagliflozin are recommended by for certain kidney patients by the UK’s regulatory bodies.
Both empagliflozin (eg Jardiance) and dapagliflozin (eg Forxiga) are only offered as additional medications for patients already on the maximum tolerated dose of ACE inhibitors or ARBs, unless these are unsuitable for the patient. Patients suitable for empagliflozin or dapagliflozin will have:
- an eGFR (measure of kidney function) between 20 and 44 ml/min/1.73 m2
or
- an eGFR of 45 to 90 ml/min/1.73 m2 with either:
- a urine albumin-to-creatinine ratio of 22.6 mg/mmol or more
or
- a urine albumin-to-creatinine ratio of 22.6 mg/mmol or more
- Type 2 diabetes
How did researchers first find out about the protective effect on kidney function?
SGLT2i’s were first studied in big clinical trials involving people living with diabetes, some of whom also had kidney disease; positive impacts were seen in both groups. This led to trials in CKD patients with and without diabetes, which confirmed SGLT2i’s could offer important benefits, reducing the risk of disease progression and death from kidney or cardiovascular causes (heart health being a serious problem as kidney function decreases).
Can children benefit from these medications?
There currently isn’t evidence for using these drugs in children with kidney disease, but the LifeArc-Kidney Research UK centre for rare diseases will be launching a clinical trial in children. We need to make sure that everyone can benefit from progress in science in a safe way.
Tell us about your research into access to these medications
We know people living in areas with more deprivation are more likely to develop kidney disease, as well as other diseases. Early studies have also shown that people living in more deprived areas of the UK are less likely to receive SGLT2i treatment when it is needed.
Using Kidney Research UK’s grant our team are looking at this in more detail, to identify what barriers might exist and how we can overcome them. Swift diagnosis is key to equal access to new treatments, and this is dependent on early GP or hospital appointments, but often those most in need are the least likely to get prompt medical care.
What needs to change so that all eligible patients have access to these vital medicines?
This is complicated, but care outside of hospitals is crucial. We need to make sure GPs have the resources to identify who would benefit from them. Currently kidney disease is not prioritised in the same way as conditions like diabetes or heart disease, which limits the time and information available to support patients. Initiatives where kidney specialists work with GPs to help improve access to treatment are likely to help, but we need to make sure the treatment gets to people who need it most, many of whom live in areas of the country with higher levels of deprivation. I hope my work with Kidney Research UK will help inform changes that are needed.
What advice would you give someone who thinks they might benefit from SGLT2i’s?
Talk to your doctor. SGLT2i treatment isn’t suitable for everyone, but this should be explained to you and an alternative plan made in partnership with you. You can show them the information in this article too.
Treating patients early with SGLT2i’s protects their kidney function, so I would encourage conversations early – as soon as any kidney damage is suspected.
Lastly, we know that the NHS is facing a crisis as the number of patients requiring dialysis is predicted to reach 143,000 by 2033, what role can new treatments play in addressing this?
SGLT2i’s are proven to slow the speed of loss of kidney function in people with chronic kidney disease. So, as well as having benefit to individual patients on their risk of heart disease and further loss of kidney function, we would expect that their widespread use would help avoid a lot of people reaching kidney failure and needing dialysis.
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