Sodium Glucose Transporter Inhibitors Explained

Sodium glucose transporter inhibitors, commonly known as SGLT2 inhibitors or gliflozins, are a class of oral medicines that have transformed the management of type 2 diabetes, heart failure, and chronic kidney disease in the UK. By blocking a kidney protein that normally returns glucose to the bloodstream, these medicines lower blood sugar, reduce blood pressure, and offer significant cardiovascular and renal protection. Licensed agents in the UK include dapagliflozin, empagliflozin, canagliflozin, and ertugliflozin. This article explains how they work, who they are suitable for, and what to watch out for.

What are sodium glucose transporter inhibitors and how do they work?

Sodium glucose transporter inhibitors block the SGLT2 protein in the kidneys, preventing glucose reabsorption and causing it to be excreted in the urine, lowering blood sugar independently of insulin. They also promote mild diuresis and natriuresis, contributing to cardiovascular and renal benefits.

Sodium glucose transporter inhibitors (also called SGLT2 inhibitors or gliflozins) are a class of oral medicines that lower blood glucose by blocking a protein in the kidneys called sodium-glucose cotransporter 2, which normally reabsorbs glucose back into the bloodstream. By inhibiting this transporter, the medicines cause excess glucose to be excreted in the urine, a process known as glucosuria, thereby reducing blood sugar levels independently of insulin. This mechanism is distinct from most other diabetes medicines, which either stimulate insulin secretion or improve insulin sensitivity.

The main SGLT2 inhibitors licensed in the UK include dapagliflozin (Forxiga), empagliflozin (Jardiance), canagliflozin (Invokana), and ertugliflozin (Steglatro).^[15][5] Each medicine has its own licensed indications and dosing schedule as set out in its UK Summary of Product Characteristics (SmPC), available on the Electronic Medicines Compendium (EMC). A related agent, sotagliflozin (Zynquista), inhibits both SGLT1 and SGLT2 transporters and has a slightly different pharmacological profile; however, sotagliflozin does not currently hold a UK marketing authorisation and is not available for routine NHS prescribing.

Beyond glucose lowering, SGLT2 inhibitors produce several additional physiological effects. They promote mild osmotic diuresis and natriuresis (sodium excretion), which reduces blood pressure and plasma volume. These effects are thought to contribute to the significant cardiovascular and renal benefits observed in large clinical trials, benefits that appear to extend beyond glycaemic control alone. The medicines are taken orally, usually once daily, and can generally be taken with or without food, though individual SmPCs should be consulted for agent-specific advice.

Which conditions are SGLT inhibitors prescribed for in the UK?

SGLT2 inhibitors are licensed in the UK for type 2 diabetes, heart failure, and chronic kidney disease, though specific indications vary by agent. Dapagliflozin and empagliflozin hold the broadest authorisations, including use in people without diabetes.

SGLT2 inhibitors are prescribed in the UK for type 2 diabetes, heart failure, and chronic kidney disease, with specific licensed indications varying between individual medicines. Dapagliflozin (Forxiga) holds MHRA authorisation for all three of these conditions, making it one of the most broadly licensed agents in this class. Empagliflozin (Jardiance) is authorised for type 2 diabetes, heart failure, and chronic kidney disease.^[9][10] Canagliflozin (Invokana) and ertugliflozin (Steglatro) are currently licensed primarily for type 2 diabetes; prescribers should consult the current SmPC for each agent to confirm the full scope of authorised indications.

For type 2 diabetes, SGLT2 inhibitors are used to improve glycaemic control, either as add-on therapy or, where metformin is not tolerated, as an alternative. In heart failure, dapagliflozin and empagliflozin are licensed for use in adults across the spectrum of ejection fraction, including heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), subject to the specific terms of each medicine's UK authorisation.^[6][11] For chronic kidney disease, dapagliflozin and empagliflozin are authorised to slow the progression of kidney disease in adults at risk of deterioration, including in people without diabetes, subject to eGFR and urinary albumin-to-creatinine ratio criteria set out in the relevant SmPC and NICE guidance.

It is important to note that the licensed indications for each medicine are distinct, and prescribers select the appropriate agent based on the individual patient's clinical profile, comorbidities, and the specific MHRA-authorised indication. Patients should not switch between agents without clinical guidance. Bolt Pharmacy is a GPhC-registered UK online pharmacy offering online consultations, with prescriber review and pharmacist support, where clinically appropriate treatment options may be considered.

How do SGLT inhibitors compare to other diabetes and heart medicines?

SGLT2 inhibitors are oral tablets with a low hypoglycaemia risk and strong evidence for reducing heart failure hospitalisations and slowing kidney disease progression, distinguishing them from sulfonylureas and GLP-1 receptor agonists. They are now a core component of guideline-directed heart failure therapy.

SGLT2 inhibitors offer a distinct combination of glucose lowering, cardiovascular protection, and renal benefits that sets them apart from older diabetes medicines such as sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, and thiazolidinediones. Unlike sulfonylureas, SGLT2 inhibitors carry a low intrinsic risk of hypoglycaemia when used without insulin or insulin secretagogues, because their mechanism does not depend on stimulating insulin release.^[1][5] However, when SGLT2 inhibitors are combined with insulin or sulfonylureas, the risk of hypoglycaemia increases, and a dose reduction of the insulin or secretagogue may be needed; patients should discuss this with their prescriber. SGLT2 inhibitors also tend to produce modest weight loss and blood pressure reduction, which are clinically useful in many patients with type 2 diabetes.

Compared with GLP-1 receptor agonists (such as semaglutide or liraglutide), SGLT2 inhibitors are oral tablets rather than injectable medicines, which some patients prefer. GLP-1 receptor agonists generally produce greater weight loss and have strong evidence for cardiovascular benefit in people with established atherosclerotic cardiovascular disease, whereas SGLT2 inhibitors show particularly strong evidence for reducing hospitalisation for heart failure and slowing kidney disease progression. In clinical practice, the two classes are sometimes used together when a patient has multiple comorbidities.

In the context of heart failure, SGLT2 inhibitors are now considered a core component of guideline-directed therapy alongside beta-blockers, ACE inhibitors or angiotensin receptor-neprilysin inhibitors (ARNIs), and mineralocorticoid receptor antagonists, as reflected in NICE technology appraisals for dapagliflozin and empagliflozin in chronic heart failure. Their ability to reduce fluid overload through diuresis complements the mechanisms of these established agents. For chronic kidney disease, they are used alongside renin-angiotensin system blockade. The choice between agents is guided by individual patient factors, tolerability, and the specific clinical indication.

What side effects should I watch out for on these tablets?

The most common side effects are genital thrush and urinary tract infections due to increased urinary glucose. Rare but serious risks include euglycaemic diabetic ketoacidosis and Fournier's gangrene, requiring urgent medical attention.

The most common side effects of SGLT2 inhibitors are genital mycotic infections (thrush) in both men and women, and urinary tract infections, both of which result from the increased glucose in the urine creating a favourable environment for microbial growth. These are generally mild and manageable with standard treatments, but patients who experience recurrent infections should discuss this with their GP. Increased urinary frequency is also common, particularly in the first few weeks of treatment. If you develop symptoms of a severe urinary infection such as high fever, shivering, back or flank pain, or feel very unwell, seek prompt medical attention as serious infections including pyelonephritis have been reported with this medicine class.

A rare but serious adverse effect is diabetic ketoacidosis (DKA), which can occur even when blood glucose levels appear only modestly elevated, a presentation sometimes called euglycaemic DKA. This risk is higher in people who are fasting, unwell, dehydrated, or who have significantly reduced their carbohydrate intake. If you feel unwell with symptoms such as nausea, vomiting, abdominal pain, excessive thirst, or rapid breathing, stop taking your SGLT2 inhibitor and seek urgent medical assessment via NHS 111 or, if severely unwell, attend A&E. If you have access to a blood ketone meter, checking your ketone level can help inform the clinical assessment. During any acute illness, dehydration, or period of reduced food and fluid intake, you should generally pause your SGLT2 inhibitor and restart it only when you have recovered and are eating and drinking normally; your GP or diabetes team can advise you on this sick-day approach.

Fournier's gangrene (necrotising fasciitis of the perineum) is an extremely rare but life-threatening infection that has been reported with SGLT2 inhibitors.^[14] Patients should seek immediate medical attention if they develop pain, tenderness, redness, or swelling in the genital or perineal area. Lower limb amputations have been reported with canagliflozin in particular, and patients should maintain good foot care and report any wounds or infections promptly to their GP.^[18][19] Volume depletion and a fall in blood pressure can also occur, particularly in older adults or those taking diuretics or medicines that affect the renin-angiotensin system; contact your GP if you feel dizzy or faint, especially on standing.

Suspected adverse reactions to SGLT2 inhibitors can be reported to the MHRA via the Yellow Card scheme at yellowcard.mhra.gov.uk. Mild side effects should be discussed with a GP or pharmacist before stopping treatment.

Who should avoid sodium glucose transporter inhibitors?

SGLT2 inhibitors are contraindicated in hypersensitivity, severe renal impairment, and pregnancy, and are not licensed for type 1 diabetes in the UK. They should be stopped before major surgery and used with caution in older adults and those at elevated DKA risk.

Sodium glucose transporter inhibitors are contraindicated in people with hypersensitivity to the active substance or any excipient listed in the relevant SmPC. SGLT2 inhibitors do not have a licensed indication for type 1 diabetes in the UK; use in type 1 diabetes is off-label and carries a substantially elevated risk of diabetic ketoacidosis, so it should only ever occur under specialist supervision if at all.

These medicines should not be initiated in people with severely reduced kidney function, as their glucose-lowering efficacy is substantially diminished at low eGFR. However, the specific eGFR threshold for initiation or continuation varies by agent and by indication: for heart failure and chronic kidney disease indications, some agents may be continued at lower eGFR values for organ-protective benefit than would apply in type 2 diabetes alone. Prescribers consult the current SmPC and relevant NICE guidance for each agent and indication when making this assessment. Renal function is checked before starting treatment and monitored periodically.

SGLT2 inhibitors should be used with caution or avoided in people who are at elevated risk of DKA, including those who are significantly restricting carbohydrate intake, following a very low calorie diet, or who have a history of recurrent DKA. They should be stopped before planned surgery or invasive procedures. UK guidance from the Joint British Diabetes Societies (JBDS) advises stopping SGLT2 inhibitors at least three days before major surgery or any procedure requiring prolonged fasting or a low-carbohydrate preparation. Patients should inform their surgical team and diabetes care team that they are taking these medicines.

Pregnancy and breastfeeding are important considerations. SGLT2 inhibitors are not recommended during pregnancy, and women of childbearing potential should use effective contraception. These medicines should be discontinued before a planned pregnancy and are not recommended during breastfeeding, as it is unknown whether they pass into human breast milk. Older adults and those taking diuretics may be at greater risk of volume depletion and should be monitored carefully, particularly at initiation. Patients with recurrent urinary tract infections or genital infections may also be less suitable candidates.

What does NICE say about prescribing SGLT inhibitors on the NHS?

NICE recommends SGLT2 inhibitors for adults with type 2 diabetes and high cardiovascular or renal risk, chronic heart failure, and chronic kidney disease, based on technology appraisals for dapagliflozin and empagliflozin. Access is subject to local Integrated Care Board commissioning decisions.

NICE recommends SGLT2 inhibitors across several clinical areas, with guidance covering type 2 diabetes, chronic heart failure, and chronic kidney disease. In its guideline on type 2 diabetes in adults (NG28, updated), NICE recommends considering an SGLT2 inhibitor with cardiovascular benefit for people with established cardiovascular disease, high cardiovascular risk, heart failure, or chronic kidney disease.^[21][22] Depending on the individual's comorbidities and risk profile, an SGLT2 inhibitor may be appropriate as an initial treatment option or as an add-on to existing therapy; the specific positioning is not fixed as second-line for all patients, and prescribers apply the guidance to each person's circumstances.

For heart failure, NICE technology appraisals have recommended dapagliflozin and empagliflozin for use within their licensed indications in adults with symptomatic chronic heart failure, across the range of ejection fraction where authorised. For chronic kidney disease, NICE has recommended dapagliflozin as an option for adults with CKD who meet specified criteria relating to eGFR and urinary albumin-to-creatinine ratio, including in people without diabetes.^[23] NHS availability following a NICE technology appraisal is subject to local commissioning decisions by Integrated Care Boards (ICBs), and access may vary across England.

NICE guidance emphasises shared decision-making, taking into account patient preferences, comorbidities, tolerability, and the overall treatment burden. Patients are encouraged to discuss with their GP or diabetes specialist whether an SGLT2 inhibitor is appropriate for them, and to review their medicines regularly. NICE does not approve medicines; it makes recommendations on clinical and cost-effectiveness for NHS use, while the MHRA is responsible for granting marketing authorisations. Patients in Scotland, Wales, and Northern Ireland should refer to guidance from the Scottish Medicines Consortium (SMC), All Wales Medicines Strategy Group (AWMSG), and the Northern Ireland formulary respectively.

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