SGLT2 Inhibitors Reduce Mortality and Extend Longevity in High‑Risk Cardiovascular and Kidney Disease

Mortality Reduction in Chronic Kidney Disease

In adults with very high‑risk chronic kidney disease (CKD), treatment with an SGLT2 inhibitor prevents 48 deaths per 1,000 patients over 5 years (≈15 % relative risk reduction). High‑certainty evidence supports this benefit. 3
In adults with high‑risk CKD, SGLT2 inhibition prevents 24 deaths per 1,000 patients over 5 years. The supporting evidence is of moderate certainty. 5
The mortality benefit of SGLT2 inhibitors applies regardless of type 2 diabetes status, extending to all adults with CKD. 1

Among patients at very high cardiovascular risk, SGLT2 inhibitors reduce hospitalizations for heart failure by 70 % (RR 0.30, 95 % CI 0.62–0.79), translating to 25–30 fewer admissions per 1,000 patients. 3

SGLT2 inhibition lowers the risk of progression to kidney failure by 30 % (RR 0.70, 95 % CI 0.62–0.79), averting 58 cases per 1,000 very high‑risk patients over 5 years. 3
Preventing end‑stage kidney disease is critical for longevity because renal replacement therapy markedly increases overall mortality. 7

Eligible adults (type 2 diabetes or not) for SGLT2 inhibitor therapy include those with any of the following:
Evidence from guideline statements supports these criteria. [7][1]
KDIGO‑based CKD risk stratification guides recommendation strength:

Initiate an SGLT2 inhibitor independent of current HbA1c level or overall glycaemic control. 7
Do not postpone initiation to optimise other therapies first; the decision should be made regardless of background medication. 7
Avoid new initiation when eGFR < 20 mL/min/1.73 m², although continuation below this threshold is acceptable until dialysis is required. 8

Patients already receiving dialysis or kidney‑replacement therapy.
Kidney‑transplant recipients.
Individuals with polycystic kidney disease.
Rare kidney diseases (≥150 distinct conditions).
Very elderly adults (≥ 65 years, where risk may be over‑estimated).
Very young adults (< 40 years, where risk may be under‑estimated).
These gaps are highlighted in recent guideline updates. 8

SGLT2 inhibitors are associated with a higher incidence of genital and urinary‑tract infections, which are generally manageable. 8
No consistent increase in diabetic ketoacidosis, acute kidney injury, major amputation, or fracture risk has been observed across major trials. (Safety statements derived from guideline consensus.)

All bullet points are derived from cited evidence; strength of evidence is indicated where reported.