Patients with autosomal dominant polycystic kidney disease were excluded from the pivotal SGLT2 inhibitor trials, which leaves nephrologists extrapolating in the commonest hereditary kidney disease and a leading cause of kidney failure. This systematic review and meta-analysis gathered what evidence exists: six clinical studies, 451 patients in total.
The results do not support extrapolation. Starting an SGLT2 inhibitor was associated with a statistically significant attenuation of eGFR decline in the first year compared with the patient's own pre-treatment slope — a mean difference of 0.65 mL/min/1.73 m2 per year (95% CI 0.05 to 1.26). But when SGLT2-treated patients were compared with patients on non-SGLT2 therapy, the difference in first-year eGFR slope was 2.12 mL/min/1.73 m2 per year with an interval of -8.13 to 12.38 — entirely uninformative. Total kidney volume, the outcome that matters mechanistically in this disease, showed no difference: mean difference -31.31 mL per year (95% CI -184.00 to 121.37).
The contrast between those two comparisons is the finding. Comparing patients with their own earlier trajectory is a weak design that is prone to regression to the mean, and it produced the only positive result. The controlled comparison, which is the one that answers the question, showed nothing measurable in either direction.
There is a theoretical concern specific to this disease that the review does not resolve. SGLT2 inhibitors increase distal sodium delivery and diuresis, and there has been debate about whether that could promote cyst growth through effects on cyclic AMP — the pathway tolvaptan targets from the other direction. The total kidney volume data here are reassuring only in that they show nothing; with intervals that wide, they cannot exclude harm any more than benefit.
So the position is unchanged: no established benefit, no identified major safety concern, and evidence limited by small samples, mostly observational designs and substantial heterogeneity. Where a patient with polycystic kidney disease has a separate indication — type 2 diabetes, heart failure — the SGLT2 inhibitor is justified on that indication. Prescribing it for the polycystic disease itself is not yet supported.
- Do not start an SGLT2 inhibitor for polycystic kidney disease itself; benefit is not established.
- Where there is a separate indication such as diabetes or heart failure, prescribe on that indication.
- The only positive result came from a before-and-after comparison, which is the weakest design here.
- Total kidney volume, the disease-specific outcome, showed no difference in either direction.
- No major safety concern was identified, but the evidence is too thin to exclude one.
The statistics, in plain English
Two comparisons, two very different qualities of evidence. Comparing each patient's eGFR slope before and after starting the drug uses the patient as their own control, which sounds efficient but is vulnerable to regression to the mean: drugs tend to be started when someone's numbers look bad, and bad numbers tend to improve on their own. That comparison was positive. The comparison against patients on other treatment — the one that actually controls for this — gave an interval of -8.13 to 12.38, which spans everything and therefore says nothing. When those two disagree, believe the controlled one.
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