What are the side effects of Glyxambi (linagliptin and empagliflozin)?

Side Effects of Glyxambi (linagliptin and empagliflozin)

Glyxambi commonly causes genital mycotic infections (especially in women), urinary tract infections, volume depletion, and joint pain, with more serious but rare side effects including diabetic ketoacidosis and acute pancreatitis. 1, 2

Common Side Effects

Genital and Urinary Tract Issues

• Genital mycotic infections occur more frequently in female patients and can be mitigated with proper genital hygiene 1, 2
• Urinary tract infections are more common in women (17-18.4% vs 3.2-4.1% in men) and patients with history of chronic or recurrent UTIs 2
• Phimosis may occur in male patients (less than 0.1-0.1%) 2

Cardiovascular and Volume-Related Effects

• Volume depletion/hypotension is particularly concerning in elderly patients and those taking diuretics 1, 2
• Increased hematocrit levels (median increase of 2.8%) may occur with empagliflozin component 2
• Peripheral edema is common with the DPP-4 inhibitor component (linagliptin) 1

Metabolic Effects

• Dose-related increases in LDL cholesterol have been observed with empagliflozin (2.3-6.5% increase) 2
• Weight loss is a common effect due to the caloric loss from urinary glucose excretion 3, 4

Musculoskeletal Effects

• Joint pain is a common side effect reported with DPP-4 inhibitors such as linagliptin 1

Serious but Less Common Side Effects

Metabolic Emergencies

• Diabetic ketoacidosis (DKA) is a rare but serious side effect that can occur even with normal blood glucose levels (euglycemic DKA) 1, 2
• Risk of DKA is higher in patients with insulin deficiency 1

Pancreatic Issues

• Acute pancreatitis has been reported with linagliptin, though causality is not firmly established 1

Allergic Reactions

• Angioedema and skin reactions (rash, urticaria) have been reported with empagliflozin 2

Infections

• Urosepsis and pyelonephritis can occur as complications of urinary tract infections 2

Special Population Considerations

Renal Function

• Empagliflozin has reduced glycemic efficacy when eGFR <45 mL/min/1.73m² 1, 2
• The medication is not recommended for patients with severe renal impairment, ESRD, or those receiving dialysis 2

Pregnancy

• Based on animal data showing adverse renal effects, Glyxambi is not recommended during the second and third trimesters of pregnancy 2

Drug Interactions

• Coadministration with diuretics increases the risk of volume depletion 2
• Combination with insulin or insulin secretagogues increases the risk of hypoglycemia 2, 4

Monitoring Recommendations

• Monitor for signs of ketoacidosis, particularly in patients with insulin deficiency 1
• Watch for symptoms of genital mycotic infections and urinary tract infections 1, 2
• Monitor for signs of volume depletion, especially in elderly patients or those on diuretics 1, 2
• Be aware that SGLT2 inhibitors interfere with urine glucose tests and 1,5-AG assays; use alternative methods to monitor glycemic control 2

Clinical Pearls

• The combination of empagliflozin and linagliptin has complementary mechanisms of action that improve glycemic control through different pathways 3, 5
• The risk of hypoglycemia is low unless combined with sulfonylureas or insulin 4, 5
• The combination provides additional benefits beyond glycemic control, including weight loss and blood pressure reduction 3, 6
• Unlike some other DPP-4 inhibitors (e.g., saxagliptin), linagliptin has shown a neutral effect on heart failure risk 1