🎙️ Episode 19: Metformin's Stage 4 Surprise – A CKD Curveball

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🧠 Clinical Context
We’ve long been taught to stop metformin once GFR drops below 30 due to concerns about lactic acidosis. But what if—just maybe—some patients might actually do better by continuing it? Enter a large-scale Scottish national database review that turned this dogma on its head.
🧪 Study Highlights

• Design: Retrospective analysis of a national database in Scotland
• Population: Patients with Stage 4 and 5 CKD (GFR ＜30 mL/min) who continued metformin for over 6 months despite guidelines
• Group Division:
• Continued metformin past GFR ＜30
• Stopped metformin upon reaching GFR ＜30

📈 Outcomes

• Mortality:
• Patients who continued metformin had lower 3-year all-cause mortality compared to those who stopped
• Cause of Death:
• Leading causes in both groups: cancer, respiratory disease, cardiovascular events
• Interestingly, respiratory deaths were significantly lower in those who stayed on metformin
• CV Events: No significant difference in major adverse cardiovascular outcomes between the groups

⚠️ Caveats

• Not a randomized trial — many possible confounders
• Nearly half of those continuing metformin eventually stopped due to provider decision or follow-up
• Mechanism for fewer respiratory deaths is unknown — could be unrelated or due to unmeasured factors

🧩 Clinical Takeaway
This accidental natural experiment suggests we might be a bit too strict with our GFR ＜30 cutoff. While lactic acidosis risk is real, the data hints that patients with stable CKD might tolerate metformin better than previously thought.
💡 Time to rethink? Maybe. But we still need prospective trials to safely redraw the lines. For now, this is not a green light, but definitely a yellow one.
Data Source: Scottish National Database, observational cohort

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