In type 2 diabetes, SGLT2 inhibitors and GLP-1 agonists protected the kidney only when albuminuria was present

Design

Target trial emulation using linked records and claims

Population

75,455 adults with type 2 diabetes on metformin, eGFR 45 or above

Primary outcome

Doubling of creatinine or eGFR below 15 over five years

Effect

With albuminuria RR 0.60 (0.42 to 0.82); without RR 1.10 (0.90 to 1.38) vs DPP-4 inhibitors

A target trial emulation in the BMJ (16 September 2026) used linked health records and claims from ten US health systems and two national insurers. It followed 75,455 people with type 2 diabetes on metformin, eGFR 45 or above and moderate cardiovascular risk, who added a GLP-1 receptor agonist or SGLT2 inhibitor, a sulfonylurea or a DPP-4 inhibitor. Most (82%) had no albuminuria, and median eGFR was 92.

The outcome was doubling of creatinine or eGFR below 15. In people with albuminuria (urine albumin-creatinine ratio 30 mg/g or more), five-year risk was 3.2% on GLP-1 agonists or SGLT2 inhibitors against 5.4% on DPP-4 inhibitors (RR 0.60, 95% CI 0.42 to 0.82). Without albuminuria it was 2.4% against 2.1% (RR 1.10, 0.90 to 1.38).

This is observational, and the two drug classes were pooled. Over a median of 32 months, people without albuminuria had few kidney events to prevent, so absence of benefit here is not proof of none over a longer horizon. These drugs have cardiovascular and weight reasons for use regardless.

The practical point is the albumin-creatinine ratio: it identifies who stands to gain the kidney benefit, and it is too often not measured.

• Check a urine albumin-creatinine ratio in every person with type 2 diabetes at least yearly
• Where albuminuria is present, prioritise an SGLT2 inhibitor or GLP-1 agonist for kidney protection
• Do not promise kidney protection to a patient with normal albumin and good eGFR — the benefit was not seen here
• Keep cardiovascular and weight indications separate from the kidney question when choosing second-line therapy
• Confirm albuminuria on two of three samples before labelling it

Why it matters

It challenges the assumption that these drugs protect every diabetic kidney equally, and makes an under-ordered test the deciding factor.

Don't overread it

This is an observational emulation over about three years; it does not show these drugs are useless for the kidney without albuminuria in the long term.

The statistics, in plain English

A risk ratio of 0.60 with albuminuria means 40% fewer kidney events, and the interval (0.42 to 0.82) stays below 1. Without albuminuria the ratio of 1.10 has an interval from 0.90 to 1.38 that includes no effect, and the absolute risks (2.4% vs 2.1%) were both low.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.