Side Effects of Glyxambi (linagliptin and empagliflozin)
Glyxambi (empagliflozin/linagliptin) has several important side effects, with the most common being genital mycotic infections, urinary tract infections, and increased urination related to the empagliflozin component, while the linagliptin component may cause joint pain and rarely pancreatitis. 1, 2
Common Side Effects
SGLT2 Inhibitor (Empagliflozin) Related:
- Genital mycotic infections: More common in females; can be mitigated with proper genital hygiene 1, 2
- Urinary tract infections: More frequent in women (17-18% vs 3-4% in men); may require treatment discontinuation in some cases 2
- Increased urination: Due to the glucose-lowering mechanism that increases urinary glucose excretion 2, 3
- Volume depletion/hypotension: Particularly in elderly patients or those taking diuretics 1
- Increased LDL cholesterol: Dose-related increases of 4.6-6.5% compared to placebo 2
- Increased hematocrit: Median increase of 2.8% 2
DPP-4 Inhibitor (Linagliptin) Related:
- Joint pain: Common side effect reported with DPP-4 inhibitors 1
- Peripheral edema: Common with DPP-4 inhibitors 1
Serious but Less Common Side Effects
SGLT2 Inhibitor (Empagliflozin) Related:
- Diabetic ketoacidosis (DKA): Rare but serious; can occur even with normal blood glucose levels (euglycemic DKA) 1, 2
- Necrotizing fasciitis of the perineum (Fournier's gangrene): Rare but requires prompt treatment if suspected 2
- Acute kidney injury: Risk increases with volume depletion 2
DPP-4 Inhibitor (Linagliptin) Related:
- Acute pancreatitis: Has been reported, though causality not firmly established 1
- Heart failure risk: While saxagliptin (another DPP-4 inhibitor) increases heart failure risk, linagliptin has shown a neutral effect on heart failure 1
Drug Interactions
- Diuretics: Increased risk of volume depletion when combined with empagliflozin 2
- Insulin or insulin secretagogues: Increased risk of hypoglycemia when combined with Glyxambi 2, 3
Special Population Considerations
- Renal impairment: Empagliflozin has reduced glycemic efficacy when eGFR <45 mL/min/1.73m² 1
- Elderly patients: Higher risk of volume depletion and hypotension 3
- Pregnancy: Not recommended during second and third trimesters due to potential adverse renal effects observed in animal studies 2
Monitoring Recommendations
- Renal function: Monitor upon initiation, especially in patients at risk for volume depletion 2
- Signs of ketoacidosis: Particularly in patients with insulin deficiency 1
- Genital symptoms: Watch for signs of infection, particularly in women 2
- Volume status and blood pressure: Especially important when ill or fasting 2
- LDL cholesterol: Monitor for clinically significant increases 2
Risk Mitigation Strategies
- Genital infections: Maintain good genital hygiene 2
- DKA risk: Implement sick-day planning; discontinue before scheduled surgery (3-4 days), during critical illness, or prolonged fasting 2
- Volume depletion: Pay attention to volume status and blood pressure, particularly when ill 2
- Hypoglycemia: Use caution when combining with insulin or insulin secretagogues 2, 3
Glyxambi combines the benefits of both drug classes, providing improved glycemic control with a modest reduction in body weight and blood pressure without significant safety issues when used appropriately 4, 5.