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SGLT2 inhibitors and cardiorenal protection

Use SGLT2 inhibitors for appropriate glycaemic, heart and kidney benefit while preventing euglycaemic ketoacidosis, dehydration, genital infection and perioperative harm.

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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.

Open the sections you need. The overview is shown first.
01Purpose and principlesWhat the treatment does and how it fits into care.

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.
  • 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.
02Indications, selection and cautionsWho may benefit, who needs urgent treatment and important alternatives.
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.

03Assessment before treatmentTests and checks that guide safe selection.
Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

  1. 01
    eGFR 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.
  2. 02
    Blood 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.
  3. 03
    Renal 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.
  4. 04
    Glucose 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.
  5. 05
    Perineal 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.
  6. 06
    Medicine 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.
  7. 07
    Heart 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.
04Treatment approachPreparation, options, escalation and aftercare.
01InitiationStart for the right indicationFirst stepType 2 diabetes, heart failure or CKD meets current NICE and licensed criteria.
  1. 1Confirm product-specific indication, eGFR, albuminuria, blood pressure, volume status, diabetes type, ketone risk, foot disease, genital infection history and pregnancy status.
  2. 2Reconcile diuretics, insulin and sulfonylureas, correcting volume depletion and avoiding abrupt insulin reduction; explain that kidney and heart benefit can exceed the glucose effect.
  3. 3Provide written DKA symptoms, blood-ketone, sick-day, fasting, surgery, genital hygiene and urgent perineal or foot warning advice before the first dose.
  4. 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 interruptionVomiting, diarrhoea, fever, dehydration, reduced intake or acute serious illness.
  1. 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.
  2. 2Seek urgent care for positive or rising ketones, abdominal pain, deep breathing, drowsiness, persistent vomiting or inability to hydrate, regardless of glucose level.
  3. 3Clinicians should assess gas, ketones, electrolytes, renal function and precipitant and use the current JBDS DKA pathway when criteria are met.
  4. 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.
  1. 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.
  2. 2Monitor blood rather than urine ketones during hospital interruption when clinically indicated, while ensuring basal insulin continues in insulin-deficient diabetes.
  3. 3Use an agreed glucose management plan through fasting and surgery and investigate acidosis or nausea promptly instead of attributing it to anaesthesia alone.
  4. 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.
  1. 1Stop the drug, begin ABCDE assessment and obtain blood ketones, venous gas, electrolytes, glucose, renal function and infection or surgical evaluation without delay.
  2. 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.
  3. 3Involve diabetes specialists and identify fasting, illness, low-carbohydrate intake, insulin reduction, alcohol or misclassified type 1 diabetes as potential triggers.
  4. 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.
05Regimens, contraindications and interactionsTreatment details and the circumstances that modify them.
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.

06Complications, monitoring and follow-upAdverse effects, response and longer-term review.
  • 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.
07Special situationsVariants, exceptions and circumstances that change the usual approach.

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.

08Common pitfallsFrequent interpretation and management errors.
  1. 01

    Excluding DKA because glucose is below the usual hyperglycaemic range.

  2. 02

    Stopping basal insulin when an SGLT2 inhibitor is initiated or withheld.

  3. 03

    Restarting immediately after surgery before ketones and intake are normal.

  4. 04

    Calling every early eGFR dip nephrotoxicity without assessing volume and trajectory.

  5. 05

    Missing Fournier gangrene by treating severe perineal pain as simple candidiasis.

  6. 06

    Using an old type 1 dapagliflozin indication as current UK authorisation.

Practice

Two practice questions

Question 1 of 20 correct
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.

Authoring stateComplete draftClinical stateAwaiting reviewJurisdictionUnited Kingdom