Mounjaro (Tirzepatide) and High Anion Gap Metabolic Acidosis
Mounjaro (tirzepatide) itself is not directly associated with high anion gap metabolic acidosis based on current evidence, unlike SGLT2 inhibitors which can cause euglycemic ketoacidosis. While GLP-1 receptor agonists like Mounjaro have various side effects, high anion gap metabolic acidosis is not a recognized direct complication of this medication class 1.
Mechanisms of High Anion Gap Metabolic Acidosis
High anion gap metabolic acidosis occurs when there is accumulation of acid anions in the blood, resulting in an elevated anion gap (typically >12 mEq/L). Common causes include:
- Lactic acidosis (tissue hypoperfusion, sepsis)
- Ketoacidosis (diabetic, alcoholic, starvation)
- Renal failure (uremic acidosis)
- Toxic ingestions (methanol, ethylene glycol, salicylates)
- Medication-induced acidosis 2, 3
Medication Classes Known to Cause High Anion Gap Metabolic Acidosis
Several medications can cause high anion gap metabolic acidosis:
- SGLT2 inhibitors: Can cause euglycemic diabetic ketoacidosis, especially perioperatively 1
- Biguanides (metformin): Can cause lactic acidosis, particularly in renal impairment
- Salicylates: Direct toxicity causing metabolic acidosis
- Alcohols and glycols: Metabolized to organic acids 4
Mounjaro (Tirzepatide) and Acid-Base Balance
Tirzepatide is a dual GIP/GLP-1 receptor agonist that:
- Enhances glucose-dependent insulin secretion
- Decreases glucagon secretion
- Slows gastric emptying
- Reduces appetite
Unlike SGLT2 inhibitors, which can cause ketoacidosis by:
- Lowering glucose concentrations
- Changing insulin/glucagon ratio
- Predisposing to ketosis during physiological stress 1
GLP-1 receptor agonists like tirzepatide do not have this mechanism of action and are not associated with ketoacidosis or high anion gap metabolic acidosis in the current literature.
Clinical Considerations
When evaluating unexplained high anion gap metabolic acidosis in patients on multiple medications:
- Calculate and correct anion gap for albumin level
- Compare to patient's baseline anion gap rather than population normal
- Assess relationship between changes in bicarbonate and anion gap
- Consider uncommon causes like 5-oxoproline acidosis if common causes are ruled out 3
Monitoring Recommendations
For patients on Mounjaro:
- Regular monitoring of renal function is prudent, as impaired kidney function can lead to metabolic acidosis
- Be vigilant for symptoms like nausea, vomiting, malaise, and confusion that could indicate an underlying acid-base disturbance
- If acidosis develops, perform comprehensive workup including arterial blood gases, serum electrolytes with calculated anion gap, serum ketones, lactate, glucose, and renal function tests 2
Important Distinctions
While SGLT2 inhibitors have a documented risk of euglycemic ketoacidosis (with an odds ratio of 1.48 compared to non-users) 1, GLP-1 receptor agonists like Mounjaro do not share this risk profile. The perioperative management guidelines for these medication classes differ accordingly, with SGLT2 inhibitors requiring careful perioperative management to prevent ketoacidosis.
If a patient on Mounjaro develops high anion gap metabolic acidosis, clinicians should investigate other common causes rather than attributing it directly to the medication.