Which medications should be stopped or adjusted in an insulin-treated patient when starting a very low-carbohydrate diet (VLCKD)?

Medications to Stop or Adjust When Starting VLCKD in Insulin-Treated Patients

When starting a very low-carbohydrate ketogenic diet (VLCKD) in insulin-treated patients, SGLT2 inhibitors should be temporarily stopped due to increased risk of diabetic ketoacidosis, and insulin doses should be reduced by 10-20% initially with close monitoring for hypoglycemia. 1

Medications That Should Be Stopped

Highest Priority to Stop

• SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin, canagliflozin)
  • These must be discontinued due to significantly increased risk of diabetic ketoacidosis (DKA) when combined with VLCKD 1, 2
  • The incidence of DKA in patients with type 2 diabetes on VLCKD who are also taking SGLT2 inhibitors is 2.90 per 1000 patient-years, compared to 1.01 per 1000 patient-years in those not taking SGLT2 inhibitors 2

Other Medications to Consider Stopping

• Sulfonylureas (e.g., glipizide, glimepiride)

  • These medications stimulate insulin release regardless of blood glucose levels and can cause hypoglycemia when carbohydrate intake is severely restricted 1
  • If a patient has already taken their daily dose, they should be instructed to consume some carbohydrates until the medication effect wears off (12-24 hours) 1

• Meglitinides (e.g., repaglinide, nateglinide)

  • Similar to sulfonylureas, these medications can cause hypoglycemia when combined with VLCKD 1

Medications That Require Adjustment

Insulin

• Reduce basal insulin dose by 10-20% initially 1

  • Further adjustments should be based on blood glucose monitoring
  • More frequent monitoring (every 4-6 hours while awake) is essential during the transition 1
  • Consider even greater reductions in insulin doses for patients with good glycemic control before starting VLCKD 3

• Bolus/mealtime insulin

  • Significant reduction is typically needed due to dramatically reduced carbohydrate intake 1
  • Adjust based on carbohydrate counting and postprandial glucose levels 1
  • Consider checking glucose 3 hours after eating to determine if additional insulin adjustments are required 1

Metformin

• Can generally be continued but may need dose reduction
  • Consider reducing dose if hypoglycemia occurs 1
  • Particularly important to adjust in patients with impaired renal function (eGFR <45 ml/min/1.73m²) 1

GLP-1 Receptor Agonists (e.g., liraglutide, semaglutide)

• May need dose adjustment based on individual response
  • Some guidelines suggest temporary discontinuation 1
  • However, many patients can continue these medications as they do not typically cause hypoglycemia when used without insulin or sulfonylureas 1

Monitoring Recommendations

• Blood glucose monitoring

  • Increase frequency to every 4-6 hours while awake during the transition period 1
  • Continue until glucose patterns stabilize on the new diet

• Ketone monitoring

  • Patients should check ketone levels, especially those previously on SGLT2 inhibitors or insulin 1
  • Blood ketone monitoring is preferred over urine ketone testing 1

• Symptoms to watch for

  • Hypoglycemia: shakiness, confusion, sweating, irritability 1
  • DKA: nausea, vomiting, abdominal pain, fruity breath odor, rapid breathing 1

Special Considerations

• Glucagon effectiveness

  • Low-carbohydrate diets impair the effectiveness of glucagon for treating hypoglycemia 4
  • This is because glucagon works primarily by stimulating glycogen breakdown in the liver, and glycogen stores are reduced on VLCKD 4

• Resuming medications

  • Medications should be resumed at usual doses within 24-48 hours of returning to normal eating patterns 1
  • For medications that can cause hypoglycemia, they should be resumed at usual doses as soon as symptoms improve and normal eating resumes 1

• Duration of medication adjustments

  • Most medication adjustments should be maintained as long as the patient remains on VLCKD 1
  • Regular reassessment is necessary as insulin sensitivity often improves over time on VLCKD, potentially requiring further dose reductions 5

Cautions and Contraindications

• VLCKD is not currently recommended for pregnant or lactating individuals, children, people with renal disease, or those with or at risk for disordered eating 1

• Patients with type 1 diabetes require particularly careful monitoring when following VLCKD due to higher risk of DKA 2, 6

• The effectiveness of VLCKD in improving glycemic control is well-documented for up to 6 months, with some benefits persisting for up to 12 months 5