When can metformin (biguanide) be resumed after a diabetic ketoacidosis (DKA) episode?

Resuming Metformin After Diabetic Ketoacidosis (DKA)

Metformin therapy should be resumed only after complete resolution of ketosis/ketoacidosis in patients who have experienced DKA. 1

Timing of Metformin Resumption

• Metformin should be restarted only after acidosis has completely resolved and normal or near-normal fasting and postprandial glycemia have been restored 1
• Initial insulin therapy is required during the acute DKA phase until ketosis/ketoacidosis has resolved 1
• After resolution of DKA, if the patient was previously on metformin, it can be resumed as part of the ongoing diabetes management plan 1

Considerations for Restarting Metformin

Kidney Function Assessment

• Before resuming metformin, assess kidney function with eGFR measurement 1
• Follow FDA guidance regarding metformin use based on eGFR levels 1:
  • Contraindicated if eGFR < 30 mL/min/1.73 m² 1
  • Reassess benefits and risks if eGFR falls to < 45 mL/min/1.73 m² 1
  • Do not initiate if eGFR < 45 mL/min/1.73 m² 1
  • Consider dose reduction in proportion to GFR decline 1

Risk Factors to Consider

• Evaluate for risk factors that might have contributed to DKA development 2, 3
• Assess for conditions that increase risk of lactic acidosis when using metformin (severe dehydration, heart failure, liver disease) 1, 3
• Consider whether the patient can adhere to "sick-day rules" (temporarily stopping metformin during acute illness, surgery, or other situations with risk of acute kidney injury) 1

Transitioning from Insulin to Metformin

• In patients initially treated with insulin and metformin who are meeting glucose targets based on blood glucose monitoring, insulin can be tapered over 2–6 weeks by decreasing the insulin dose by 10–30% every few days 1
• Continue blood glucose monitoring to ensure adequate glycemic control during the transition period 1
• For patients with type 2 diabetes who presented with DKA, consider maintaining both insulin and metformin if needed for glycemic control 1

Special Considerations

Concurrent Use with SGLT2 Inhibitors

• Exercise caution when restarting combination therapy with metformin and SGLT2 inhibitors, as this combination has been associated with increased risk of euglycemic DKA 3
• Consider delaying SGLT2 inhibitor restart until stable on metformin alone 3

Monitoring After Resumption

• Monitor blood glucose levels closely after resuming metformin 1
• Assess for signs of recurrent ketosis or acidosis 1
• Consider more frequent follow-up visits initially after DKA episode 1

Pitfalls to Avoid

• Resuming metformin too early before complete resolution of acidosis can potentially worsen metabolic derangements 2
• Failing to identify the underlying cause of DKA may lead to recurrence 4
• Not providing adequate patient education about sick-day management and when to temporarily discontinue metformin 1
• Overlooking the need to adjust metformin dosing based on kidney function 1
• Neglecting to monitor for potential complications after resuming therapy 1