SGLT2 inhibitors and GLP-1 agonists were linked to kidney protection only when albuminuria was present

Design

Target trial emulation using linked records and claims (BESTMED)

Population

75,455 US adults with type 2 diabetes, eGFR ≥45, starting second-line therapy after metformin

Primary outcome

Doubling of serum creatinine or eGFR below 15

Effect

With albuminuria: five-year risk 3.2% vs 5.4%, RR 0.60 (95% CI 0.42 to 0.82); without: RR 1.10 (0.90 to 1.38)

BESTMED used linked health records and insurance claims from 10 US health systems and two national insurers to emulate a trial in 75,455 people with type 2 diabetes, eGFR of 45 or more and moderate cardiovascular risk, who started a second drug after metformin between 2014 and 2022. Most (82%) had no albuminuria; median eGFR was 92.

The outcome was doubling of creatinine or eGFR below 15. In people with albuminuria (urine albumin-to-creatinine ratio 30 mg/g or more), the estimated five-year risk was 3.2% with a GLP-1 receptor agonist or SGLT2 inhibitor against 5.4% with a DPP-4 inhibitor (risk ratio 0.60, 95% CI 0.42 to 0.82). Without albuminuria, risks were 2.4% vs 2.1% (risk ratio 1.10, 0.90 to 1.38).

The point for any prescriber is that the albumin-to-creatinine ratio identifies who stands to gain kidney protection from these drugs. Without it, the kidney argument for choosing them over a DPP-4 inhibitor was weak over about three years, although the cardiovascular and weight arguments may still apply.

• Check urine albumin-to-creatinine ratio before choosing a second-line diabetes drug, not only eGFR.
• With albuminuria present, favour an SGLT2 inhibitor or GLP-1 receptor agonist for kidney protection.
• Without albuminuria, decide on cardiovascular risk, weight and cost rather than expected kidney benefit.
• Repeat the albumin-to-creatinine ratio at least yearly; a new rise changes the choice.

Why it matters

It turns albuminuria from a monitoring test into the deciding factor for which second-line drug protects the kidney.

Don't overread it

This is observational; target trial emulation reduces bias but cannot match randomisation, and the drug classes were pooled.

The statistics, in plain English

A risk ratio of 0.60 means about 40% less kidney deterioration over five years in the albuminuria group. In people without albuminuria, the interval runs from 0.90 to 1.38 and includes 1, so no benefit was shown, though follow-up (median 32 months) may be too short to see one.

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