Separate comparisons with DPP-4 inhibitors do not show a treatment hierarchy

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Dear Editor,

Turchin and colleagues report that among people without albuminuria, the estimated five-year risk of renal deterioration was 2.8% with sulfonylureas, 2.4% with GLP-1 receptor agonists or SGLT2 inhibitors, and 2.1% with DPP-4 inhibitors.[1] Compared with DPP-4 inhibitors, the risk ratio was 1.31 (95% CI 1.11 to 1.58) for sulfonylureas and 1.10 (0.90 to 1.38) for GLP-1 receptor agonists or SGLT2 inhibitors.

These results may give the impression that sulfonylureas have worse renal outcomes than GLP-1 receptor agonists or SGLT2 inhibitors. However, that comparison was not made. Both risk ratios use DPP-4 inhibitors as the reference. The fact that one comparison is statistically significant and the other is not does not show that the two active treatment strategies differ from each other. A direct comparison between them, with its own confidence interval, would be needed to support that conclusion. The supplementary analyses report GLP-1 receptor agonists and SGLT2 inhibitors separately, but these estimates also remain comparisons with DPP-4 inhibitors rather than with sulfonylureas.[1]

This is relevant to the suggestion that albuminuria could help guide treatment choice. In people without albuminuria, the study shows a higher estimated renal risk with sulfonylureas than with DPP-4 inhibitors, while there is little evidence of a difference between GLP-1 receptor agonists or SGLT2 inhibitors and DPP-4 inhibitors. It does not show that sulfonylureas are worse than GLP-1 receptor agonists or SGLT2 inhibitors.

These findings should therefore not be used to rank the active drug classes by renal outcomes without a direct comparison between them.

Reference

1. Turchin A, Petito LC, Hegermiller E, et al. Renal outcomes in people with type 2 diabetes with and without albuminuria treated with SGLT-2 inhibitors and GLP-1 receptor agonists: target trial emulation. BMJ 2026;394:e100574. doi:10.1136/bmj-2026-100574.

No competing Interests: YesThe following competing Interests: Electronic Publication Date: Friday, September 18, 2026 - 15:50AI use: Yes I have used AIAI use details: ChatGPT was used solely for English language translation and for improving grammar and spelling. All scientific content, interpretation, arguments, and conclusions were developed and verified by me. I take full responsibility for the final content of the manuscript.Highwire Comment Subject:

Renal outcomes in people with type 2 diabetes with and without albuminuria treated with SGLT-2 inhibitors and GLP-1 receptor agonists: target trial emulation

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Separate comparisons with DPP-4 inhibitors do not show a treatment hierarchy

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Renal outcomes in people with type 2 diabetes with and without albuminuria treated with SGLT-2 inhibitors and GLP-1 receptor agonists: target trial emulation

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