SGLT2 inhibitors in diabetic CKD: weight, pressure and glucose improved, eGFR and UACR unchanged in pooled trials

Design

Systematic review and meta-analysis of 17 randomised trials

Population

29,192 participants with diabetic CKD

Primary outcome

eGFR and UACR; secondary glycaemic, weight and blood pressure outcomes; safety

Effect

HbA1c -0.40 (95% CI -0.44 to -0.36); eGFR +0.25 (-0.08 to 0.57); volume depletion RR 1.36 (1.16 to 1.59)

This systematic review and meta-analysis pooled 17 randomised trials with 29,192 participants with diabetic CKD. Outcomes were grouped as renal surrogates (eGFR, UACR), metabolic and haemodynamic measures, and safety.

SGLT2 inhibitors lowered HbA1c by 0.40 percentage points (95% CI -0.44 to -0.36), body weight by 1.36 kg and systolic pressure by 2.98 mmHg (-3.44 to -2.52). There was no significant difference in eGFR (mean difference 0.25 mL/min/1.73 m2, -0.08 to 0.57) or UACR (-31.6 mg/g, -137.2 to 74.1). Urinary infections were not significantly more frequent (RR 1.20, 0.94 to 1.54), but volume-depletion events were (RR 1.36, 1.16 to 1.59).

The neutral eGFR and albuminuria results reflect short to medium follow-up and a pooled surrogate analysis. The authors point out that large outcome trials show long-term cardiorenal protection, which this analysis does not replace.

• Do not read the neutral eGFR result as a lack of kidney protection; this analysis looked at short-term surrogates.
• Expect modest falls in weight (about 1.4 kg) and systolic pressure (about 3 mmHg).
• Check for volume depletion, especially with diuretics or in older patients; events were 36% more frequent.
• Urinary infection risk was not significantly higher in pooled data.

Why it matters

It separates the metabolic effects of these drugs from the long-term kidney protection shown in outcome trials.

Don't overread it

The pooled surrogate results do not contradict outcome trials of long-term kidney protection.

The statistics, in plain English

A mean eGFR difference of 0.25 with an interval from -0.08 to 0.57 shows no change in this measure across the trials, but eGFR dips early on these drugs and recovers, so it is a poor guide to long-term benefit. The UACR interval is very wide and spans large reductions and increases.

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