Can Ozempic (semaglutide) and Jardiance (empagliflozin) cause hypoglycemia in patients with type 2 diabetes?

Hypoglycemia Risk with Ozempic (Semaglutide) and Jardiance (Empagliflozin)

Both Ozempic (semaglutide) and Jardiance (empagliflozin) have minimal risk of causing hypoglycemia when used alone, but they may increase hypoglycemic risk when combined with insulin or sulfonylureas. 1

Mechanism of Action and Hypoglycemia Risk

GLP-1 Receptor Agonists (Ozempic/Semaglutide)

• Work by stimulating insulin secretion and reducing glucagon secretion in a glucose-dependent manner 1
• Promote weight loss and improve satiety
• Have high glucose-lowering efficacy
• Minimal risk for hypoglycemia when used as monotherapy 1
• May increase hypoglycemic potential when combined with insulin or sulfonylureas 1

SGLT2 Inhibitors (Jardiance/Empagliflozin)

• Work by inhibiting glucose reabsorption in kidneys, increasing urinary glucose excretion
• Independent of β-cell function, making them effective at any disease stage 2
• Provide moderate reductions in body weight and blood pressure 2
• Low risk of hypoglycemia except when used with insulin or insulin secretagogues 2

Clinical Evidence on Hypoglycemia Risk

Semaglutide (Ozempic)

• Clinical trials demonstrate improved glycemic control with low risk of hypoglycemia 3
• When added to oral glucose-lowering therapies, associated with low proportions of patients experiencing severe or blood glucose-confirmed symptomatic hypoglycemia 4
• Did not increase hypoglycemia incidence when added to insulin therapy 4

Empagliflozin (Jardiance)

• Phase 3 clinical trials showed no increased risk of hypoglycemia versus placebo as monotherapy 5
• No increased hypoglycemia risk when used as add-on therapy, except when given with sulfonylurea 5
• Generally well-tolerated with a favorable benefit-risk ratio 2

Important Considerations for Combined Therapy

Risk Factors for Hypoglycemia

• Concomitant use with insulin or sulfonylureas significantly increases hypoglycemia risk 1
• If HbA1c is well-controlled at baseline, or there's a known history of frequent hypoglycemic events:
  • Consider weaning or stopping sulfonylurea or glinide
  • Consider reducing total daily insulin dose by ~20% when starting SGLT2 inhibitor therapy 1

Monitoring Recommendations

• Self-monitoring of blood glucose should be considered to facilitate optimal glycemic control in T2DM 1
• Guidelines explicitly recommend avoiding hypoglycemia 1
• Hypoglycemia should be avoided as it can trigger arrhythmias 1

Safety Considerations Beyond Hypoglycemia

Empagliflozin (Jardiance)

• May cause genital fungal infections, urinary tract infections 1
• Risk of euglycemic diabetic ketoacidosis 1
• May contribute to intravascular volume contraction; consider stopping or reducing diuretic dose if applicable 1
• Should be discontinued at least 3 days before planned surgery to prevent postoperative ketoacidosis 1

Semaglutide (Ozempic)

• Gastrointestinal side effects most common (nausea, vomiting, diarrhea)
• Most GI side effects are transient and tend to occur during dose escalation 4

Clinical Decision Algorithm

1. For patients on monotherapy with either agent:

   • Monitor blood glucose but expect minimal hypoglycemia risk
   • No special precautions needed specifically for hypoglycemia

2. For patients starting either agent while on insulin:

   • Reduce total daily insulin dose by approximately 20% 1
   • Monitor blood glucose more frequently during initiation
   • Adjust insulin dose based on glucose readings

3. For patients starting either agent while on sulfonylureas:

   • Consider reducing sulfonylurea dose or discontinuing if HbA1c is near target 1
   • Monitor closely for hypoglycemia symptoms, especially during first few weeks

4. For patients on both agents together:

   • Use standard doses (Empagliflozin 10mg daily, Semaglutide as prescribed) 1
   • Monitor for additive effects on blood pressure and volume status
   • No specific increased hypoglycemia risk from the combination itself

Remember that hypoglycemia from these medications is primarily a concern when they're used in combination with insulin or insulin secretagogues, not when used as monotherapy or together.