SGLT2 inhibitors: renal mechanism, cardiorenal benefit and euglycaemic ketoacidosis
How blocking proximal tubular glucose reabsorption lowers glucose in proportion to filtered load, why tubuloglomerular feedback causes the expected eGFR dip and slows CKD, the heart failure and kidney trials with worked NNTs, and the physiology of euglycaemic ketoacidosis and perioperative withholding.
Tier 1Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- SGLT2 inhibitors (empagliflozin, dapagliflozin; canagliflozin and ertugliflozin overseas) block sodium-glucose cotransporter 2 in the proximal tubule.
- Glucose lowering is modest (HbA1c 0.5 to 0.8%) and depends on GFR. The heart failure and kidney benefits don't depend on glucose and persist at low eGFR.
- Paper 1 tests the transporter physiology, the haemodynamic eGFR dip, the mechanism of euglycaemic ketoacidosis, and trial numbers.
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Sources
- Diabetes (Therapeutic Guidelines)AU/NZTherapeutic Guidelines Ltd, 2026
- Periprocedural diabetic ketoacidosis with SGLT2 inhibitor use: ADS, ADEA, ANZCA and NZSSD alertAU/NZAustralian Diabetes Society, May 2023
- KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney diseaseKidney International 2022;102(5S):S1-S127, 2022
- KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney diseaseKidney International 2024;105(4S):S117-S314, 2024
- Dapagliflozin in patients with heart failure and reduced ejection fraction (DAPA-HF)McMurray et al., N Engl J Med 2019;381:1995-2008, 2019
- Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes (EMPA-REG OUTCOME)Zinman et al., N Engl J Med 2015;373:2117-28, 2015
- Dapagliflozin in patients with chronic kidney disease (DAPA-CKD)Heerspink et al., N Engl J Med 2020;383:1436-46, 2020
- Empagliflozin in patients with chronic kidney disease (EMPA-KIDNEY)The EMPA-KIDNEY Collaborative Group, N Engl J Med 2023;388:117-27, 2023
- Last updated
- 14 November 2026
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