Stopping Versus Continuing Metformin in Patients With Advanced CKD: A Nationwide Scottish Target Trial Emulation...

Area of Science:

• Nephrology
• Endocrinology
• Clinical Pharmacy

Background:

• Current guidelines often advise against metformin use in advanced kidney impairment, despite limited evidence.
• The impact of continuing or stopping metformin in type 2 diabetes patients with stage 4 chronic kidney disease (CKD) on mortality and cardiovascular events is unclear.

Purpose of the Study:

• To compare outcomes of patients with type 2 diabetes who continued versus stopped metformin after developing stage 4 CKD (eGFR <30mL/min/1.73m²).

Main Methods:

• Nationwide observational cohort study of adults with type 2 diabetes and incident stage 4 CKD in Scotland (2010-2019).
• Target trial emulation using clone-censor-weight design and marginal structural models.
• Primary outcome: all-cause mortality. Secondary outcome: major adverse cardiovascular events (MACE).

Main Results:

• Analysis included 4,278 patients; 40.1% discontinued metformin within 6 months of stage 4 CKD diagnosis.
• Stopping metformin was associated with lower 3-year survival (HR, 1.26; 95% CI, 1.10-1.44).
• Marginal structural models confirmed higher all-cause mortality risk (HR, 1.34; 95% CI, 1.08-1.67) and similar MACE risk (HR, 1.04; 95% CI, 0.81-1.33) for those who stopped metformin.

Conclusions:

• Continued metformin use may be appropriate for patients with stage 4 CKD (eGFR <30mL/min/1.73m²).
• Stopping metformin was associated with reduced survival, not explained by increased cardiovascular events.
• Randomized controlled trials are necessary to confirm these findings.