Higher diversity of anti-diabetic therapy is associated with lower risk of major adverse kidney events in diabetes

Table 2 Effects of combination anti-diabetic therapy vs monotherapy on risk of major adverse kidney events.

Characteristic	Case/total		HR (95%CI)
	Monotherapy	Combination therapy
UK Biobank: Intention-to-treat analysis
Unadjusted model	83/3475	54/3475	0.65 (0.46-0.92)
Adjusting for ACEI/ARB and MRA use at baseline	83/3475	54/3475	0.65 (0.46-0.92)
Excluding ACEI/ARB users at baseline	68/2795	40/2790	0.65 (0.46-0.93)
Excluding MRA users at baseline	78/3419	51/3428	0.59 (0.40-0.87)
Chongqing Diabetes Registry: Per-protocol analysis
Unadjusted model	19/261	13/808	0.24 (0.11-0.55)
Adjusting for ACEI/ARB, MRA, SGLT2i, and GLP-1RA use at baseline or during follow-up	19/261	13/808	0.37 (0.16-0.88)
Excluding ACEI/ARB users at baseline or during follow-up	9/157	4/373	0.25 (0.07-0.95)
Excluding MRA users at baseline or during follow-up	19/258	12/797	0.24 (0.11-0.55)
Excluding SGLT2i users at baseline or during follow-up	19/203	6/288	0.30 (0.10-0.87)
Excluding GLP-1RA users at baseline or during follow-up	19/251	9/640	0.22 (0.09-0.56)

The major adverse kidney events are a composite of end-stage renal disease (defined as estimated glomerular filtration rate ≤ 15 mL/minute/1.73 m², initiation of dialysis, or undergoing kidney transplantation) or death attributed to kidney disease. Monotherapy: With a single anti-diabetic medication. Combination therapy: With ≥ 2 anti-diabetic medications. HR: Hazard ratio; CI: Confidence interval; ACEI: Angiotensin-converting enzyme inhibitor; ARB: Angiotensin receptor blocker; MRA: Mineralocorticoid receptor antagonist; SGLT2i: Sodium-glucose cotransporter-2 inhibitor; GLP-1RA: Glucagon-like peptide-1 receptor agonist.