Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.
SGLT2 inhibitors and cardiorenal protection
Endocrinology and metabolism · UK scope · Sources checked 27 Aug 2026 · Clinical review pending
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Time-critical presentation
Nausea, vomiting, abdominal pain, deep breathing, confusion or unusual fatigue in someone taking an SGLT2 inhibitor requires blood ketone and acid-base assessment even when glucose is near normal. Stop the drug, treat confirmed DKA urgently and do not restart after SGLT2-associated DKA unless a clear cause is identified and resolved with specialist agreement.
Purpose and principles
Use SGLT2 inhibitors for appropriate glycaemic, heart and kidney benefit while preventing euglycaemic ketoacidosis, dehydration, genital infection and perioperative harm.
By inhibiting proximal tubular glucose and sodium reabsorption, SGLT2 inhibitors reduce intraglomerular pressure and alter cardiac–renal haemodynamics. Benefits include slower kidney decline and fewer heart-failure admissions in selected people with and without diabetes, while glycosuria lowers glucose only when filtered glucose and kidney function permit.
The central decision is whether the person's indication and eGFR match a specific licensed product and NICE pathway, and whether volume status, ketosis risk, foot or genital health and ability to follow sick-day rules make treatment safe.
Prescribing for heart failure or CKD still requires diabetes safety knowledge. A person without markedly high glucose can develop ketoacidosis if insulin falls, intake stops or illness and surgery increase counter-regulatory hormones.
Key points
SGLT2 inhibitors cause urinary glucose and sodium loss, with benefits in type 2 diabetes, heart failure and chronic kidney disease that extend beyond HbA1c reduction.
Indications, selection and cautions
Expected osmotic effects
Increased urination, thirst and a small early blood-pressure fall can occur after initiation. Review diuretics and fluid status if symptoms impair function or cause postural dizziness.
Genital fungal infection
Itch, erythema, discharge or balanitis is commoner because of glycosuria and often responds to standard treatment; recurrence prompts hygiene, glucose and continuation review.
Euglycaemic ketoacidosisRed flag
Nausea, vomiting, abdominal pain, tachypnoea, drowsiness or ketone odour with only modest glucose is a time-critical SGLT2 complication, especially during fasting, illness or insulin reduction.
Volume depletionRed flag
Postural hypotension, syncope, oliguria or rising creatinine after diarrhoea, heat, diuretics or low intake indicates clinically important hypovolaemia and requires drug interruption and assessment.
Fournier gangreneRed flag
Severe perineal pain, swelling, erythema, fever or malaise may precede necrosis and requires immediate broad sepsis management and surgical referral, not treatment as simple thrush.
Foot disease concernRed flag
New ulcer, infection, ischaemic pain or gangrene needs urgent multidisciplinary foot assessment and an individual decision about treatment interruption, especially with canagliflozin or severe vascular disease.
Protective renal response
A small early eGFR fall in an otherwise well euvolaemic patient may be expected. Progressive decline, hypotension, hyperkalaemia or active urinary abnormalities points to another process.
Assessment before treatment
01eGFR and urinary albumin-to-creatinine ratioFirst step
Why
Confirm kidney indication, product eligibility and baseline risk.
Interpretation and limitations
Use current NICE and product-specific cut-offs. Cardiorenal benefit may justify use when glucose lowering is small; albuminuria and eGFR trend determine the wider kidney plan.
02Blood ketones and venous blood gas
Why
Diagnose euglycaemic or conventional DKA during compatible symptoms.
Interpretation and limitations
Prefer blood beta-hydroxybutyrate to urine during hospital interruption. Acidosis and ketonaemia define danger; normal-ish glucose must not stop the DKA pathway.
03Renal profile and volume assessment
Why
Separate expected haemodynamic dip from hypovolaemia or acute kidney injury.
Interpretation and limitations
Review blood pressure, orthostasis, weight, urine output, creatinine, sodium and potassium with diuretic and illness history. Treat physiology rather than stopping kidney-protective therapy for one small isolated change.
04Glucose and HbA1c
Why
Measure glycaemic effect separately from cardiorenal benefit.
Interpretation and limitations
Falling eGFR reduces HbA1c response; do not label the drug ineffective for CKD or heart failure solely because glucose changes little. Avoid hypoglycaemia by reviewing insulin and sulfonylurea.
Treatment approach
01InitiationStart for the right indicationFirst stepType 2 diabetes, heart failure or CKD meets current NICE and licensed criteria.+
2Reconcile diuretics, insulin and sulfonylureas, correcting volume depletion and avoiding abrupt insulin reduction; explain that kidney and heart benefit can exceed the glucose effect.
3Provide written DKA symptoms, blood-ketone, sick-day, fasting, surgery, genital hygiene and urgent perineal or foot warning advice before the first dose.
4Review renal function and tolerability at the locally specified interval, interpreting any early dip in the whole clinical context and preserving treatment when safely appropriate.
02IllnessSick-day interruption
Regimens, contraindications and interactions
Provides glucose lowering and product-specific cardiovascular, heart-failure and kidney protection.
SGLT2 inhibitor
Use the licensed product and dose for the exact diabetes, heart or kidney indication.
Check eGFR and volume, avoid routine type 1 use and pregnancy, teach euglycaemic DKA and sick-day interruption, and monitor genital, perineal and foot complications.
Prevents insulin deficiency and ketosis while SGLT2 treatment contributes cardiorenal benefit.
Insulin co-therapy
Retain essential basal insulin and adjust other doses cautiously from glucose data.
Abrupt reduction increases DKA risk and should never be made simply because an SGLT2 inhibitor starts. Monitor ketones during illness, fasting and unexplained nausea.
Treats a common glycosuria-related adverse effect and may allow beneficial therapy to continue.
Antifungal treatment
Use the current formulary topical or oral regimen for confirmed genital candidiasis.
Check pregnancy, interactions and recurrence; severe pain, fever, tissue change or systemic illness is not uncomplicated thrush and requires emergency assessment for deeper infection.
Complications, monitoring and follow-up
Review eGFR, electrolytes, blood pressure, volume status and diuretic burden after initiation according to CKD and heart-failure risk, not an inflexible universal schedule.
Track albuminuria and kidney-function slope over time; kidney benefit is assessed from trajectory and clinical outcomes, not the immediate glucose response.
Ask at every contact about fasting, illness, ketogenic diet, insulin changes, genital infection, foot lesions and whether the person remembers the DKA symptoms and stop rule.
During hospital interruption, use blood ketone monitoring when required and record the explicit restart decision after normalisation and oral intake.
Review HbA1c and hypoglycaemia with insulin or sulfonylurea co-therapy, reducing those agents rather than discarding indicated SGLT2 cardiorenal treatment without reason.
Special situations
Glucose is not the whole indication
At lower eGFR, glycosuria and HbA1c change diminish while haemodynamic kidney and heart benefits can remain. Explain this to prevent inappropriate discontinuation.
Blood ketones are preferred
SGLT2 treatment can alter urinary ketone handling, and blood beta-hydroxybutyrate better supports hospital decisions during surgery or acute illness.
A small dip may be expected
Initial glomerular haemodynamic change can lower eGFR modestly. Symptoms, volume, potassium and subsequent trend separate this from progressive acute kidney injury.
Thrush and Fournier are different
Superficial itch and discharge are common; disproportionate perineal pain, swelling and systemic toxicity is a rare surgical emergency requiring immediate escalation.
Type 1 authorisation changed
Dapagliflozin is no longer authorised for type 1 diabetes in the UK. Historic clinic notes or overseas practice should not be treated as current routine approval.
Restart is a clinical decision
The date on a perioperative chart is insufficient. Ketones, intake, haemodynamics and the reason for interruption must all be satisfactory before resumption.
Common pitfalls
01
Excluding DKA because glucose is below the usual hyperglycaemic range.
02
Stopping basal insulin when an SGLT2 inhibitor is initiated or withheld.
03
Restarting immediately after surgery before ketones and intake are normal.
04
Calling every early eGFR dip nephrotoxicity without assessing volume and trajectory.
05
Missing Fournier gangrene by treating severe perineal pain as simple candidiasis.
06
Using an old type 1 dapagliflozin indication as current UK authorisation.
Practice
Two practice questions
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Question 1 of 2
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Endocrinology and metabolismOriginal SBA
Euglycaemic illness on empagliflozin
A person taking empagliflozin presents after two days of poor intake with abdominal pain, deep breathing and glucose 11.2 mmol/L. What is the most appropriate immediate investigation?
Sources and review status5 sources · checked 27 Aug 2026 · clinical review pending+
Sources
Sources and review status
National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.
The glucose-lowering effect diminishes as eGFR falls, but kidney and heart-failure protection can persist within licensed and NICE-recommended renal ranges.
NICE's February 2026 type 2 algorithm places cardiorenal comorbidity and risk at the centre of selection; check exact product eligibility rather than treating the class as interchangeable.
Explain genital candidiasis, polyuria, volume depletion and the rare risks of ketoacidosis and Fournier gangrene before initiation, with a written sick-day plan.
SGLT2-associated DKA may be euglycaemic. Test blood ketones when symptoms fit, regardless of a reassuring capillary glucose.
Pause treatment during acute serious illness, inability to eat or drink, significant dehydration and major surgery; hospitalised patients need blood-ketone monitoring under MHRA guidance.
Do not use SGLT2 inhibitors for type 1 diabetes in routine UK practice: dapagliflozin's former type 1 indication is no longer authorised.
An early modest eGFR dip may reflect haemodynamic change and is not automatically acute kidney injury; interpret with symptoms, volume status, potassium and later trajectory.
Never reduce essential insulin abruptly when adding SGLT2 treatment, and avoid ketogenic diets or prolonged fasting that increase ketosis risk.
05Perineal and foot examination
Why
Identify infection, ischaemia or necrotising soft-tissue disease.
Interpretation and limitations
Simple candidiasis is local and superficial; systemic illness, disproportionate pain or tissue change demands emergency surgical sepsis assessment. Active foot disease needs specialist review.
06Medicine and fasting review
Why
Identify DKA and dehydration triggers before treatment or procedures.
Interpretation and limitations
Check insulin reduction, ketogenic diet, alcohol excess, recent surgery, infection, low intake, bariatric procedure and diuretic burden. A written mitigation plan is part of eligibility.
07Heart failure status
Why
Document congestion, blood pressure and therapeutic response.
Interpretation and limitations
Benefit applies across ejection-fraction phenotypes for selected licensed products, but acute decompensation, hypotension and diuretic change require coordinated cardiology and renal assessment.
Vomiting, diarrhoea, fever, dehydration, reduced intake or acute serious illness.
+
1Stop the SGLT2 inhibitor temporarily, maintain hydration and carbohydrate as able, continue essential insulin and increase glucose and blood-ketone monitoring under the person's sick-day plan.
2Seek urgent care for positive or rising ketones, abdominal pain, deep breathing, drowsiness, persistent vomiting or inability to hydrate, regardless of glucose level.
3Clinicians should assess gas, ketones, electrolytes, renal function and precipitant and use the current JBDS DKA pathway when criteria are met.
4Restart only when ketones are normal, the person is clinically stable and eating and drinking, with the cause understood and product eligibility rechecked.
03SurgeryPerioperative interruption and ketone safetyMajor operation, prolonged fasting or hospital admission for acute serious illness.+
1Identify the medicine at pre-assessment and stop it at the interval in the current local perioperative policy; different operations and pathways may require longer fasting safeguards.
2Monitor blood rather than urine ketones during hospital interruption when clinically indicated, while ensuring basal insulin continues in insulin-deficient diabetes.
3Use an agreed glucose management plan through fasting and surgery and investigate acidosis or nausea promptly instead of attributing it to anaesthesia alone.
4Resume only after normal ketones, physiological stability and reliable oral intake, with diabetes-team advice after any suspected perioperative ketoacidosis.
04DKASuspected SGLT2-associated ketoacidosisCompatible symptoms with ketonaemia or metabolic acidosis, even at near-normal glucose.+
1Stop the drug, begin ABCDE assessment and obtain blood ketones, venous gas, electrolytes, glucose, renal function and infection or surgical evaluation without delay.
2Treat confirmed DKA with the current JBDS fixed-rate insulin, fluid and potassium protocol, recognising that dextrose may be needed early because glucose is not markedly raised.
3Involve diabetes specialists and identify fasting, illness, low-carbohydrate intake, insulin reduction, alcohol or misclassified type 1 diabetes as potential triggers.
4Do not routinely restart after DKA; only reconsider when another clear cause has resolved and a specialist judges the cardiorenal benefit to outweigh recurrence risk.