Can Ozempic (semaglutide) cause metabolic acidosis?

Ozempic (Semaglutide) and Metabolic Acidosis

Based on current clinical guidelines and evidence, Ozempic (semaglutide) does not directly cause metabolic acidosis as an adverse effect. 1

Metabolic Acidosis Risk with GLP-1 Receptor Agonists

• GLP-1 receptor agonists like semaglutide are not directly associated with metabolic acidosis in major clinical guidelines 1
• The comprehensive medication summaries in current diabetes and cardiorenal disease management guidelines do not list metabolic acidosis as a side effect of GLP-1 receptor agonists 1
• The primary adverse effects of GLP-1 receptor agonists are gastrointestinal symptoms (nausea, vomiting, diarrhea), which are typically transient and occur during dose escalation 1

Indirect Mechanisms That Could Potentially Lead to Acidosis

Dehydration and Acute Kidney Injury

• GLP-1 receptor agonists can cause nausea, vomiting, and reduced oral intake, potentially leading to dehydration 1
• In the setting of volume depletion, patients may develop acute kidney injury, which could contribute to metabolic acidosis, especially if they are also taking medications like metformin 2
• Monitoring renal function is recommended when using GLP-1 receptor agonists, especially in patients with gastrointestinal symptoms that may lead to dehydration 1

Rare Case Reports

• There is a case report of euglycemic ketoacidosis in a patient without diabetes who was taking semaglutide for weight loss, though this appears to be extremely rare 3
• This type of ketoacidosis is more commonly associated with SGLT2 inhibitors rather than GLP-1 receptor agonists 3

Medication Combinations That Increase Risk

• The combination of metformin and GLP-1 receptor agonists requires careful monitoring, as metformin is associated with lactic acidosis, particularly in the setting of renal impairment 1
• Metformin is contraindicated when eGFR is <30 mL/min/1.73 m² due to increased risk of lactic acidosis 1
• Combining GLP-1 receptor agonists with SGLT2 inhibitors may potentially increase the risk of metabolic derangements, especially in the setting of volume depletion 2

Clinical Monitoring and Prevention

• Monitor renal function in patients taking semaglutide, especially those with risk factors for dehydration or renal impairment 1
• Ensure adequate hydration, particularly during dose escalation when gastrointestinal side effects are most common 1
• Be vigilant for signs of metabolic acidosis (rapid breathing, confusion, fatigue) in patients taking semaglutide who develop acute illness, especially with vomiting or reduced oral intake 1
• Consider checking electrolytes, renal function, and acid-base status in patients on semaglutide who present with significant gastrointestinal symptoms or signs of dehydration 2

Special Considerations

• Elderly patients may be at higher risk for dehydration and subsequent complications when taking GLP-1 receptor agonists 2
• Patients with pre-existing renal impairment require closer monitoring when using semaglutide 1
• Pre-treatment assessment before initiating semaglutide should include baseline renal function 4

In conclusion, while semaglutide itself does not directly cause metabolic acidosis according to current guidelines, clinicians should be aware of potential indirect mechanisms and risk factors that could lead to acid-base disturbances in certain clinical scenarios.