Does Empagliflozin (Jardiance) cause diarrhea?

Empagliflozin and Diarrhea: Clinical Evidence and Management

Empagliflozin (Jardiance) does not commonly cause diarrhea as a side effect, unlike some other antidiabetic medications in different classes.

Evidence on Empagliflozin and Gastrointestinal Effects

• The most common adverse effects of empagliflozin include genital mycotic infections (particularly in women), urinary tract infections, volume depletion effects, and risk of euglycemic ketoacidosis 1.
• Clinical trials evaluating empagliflozin, including EMPA-RESPONSE-AHF, did not report diarrhea as a significant adverse event 2.
• Empagliflozin's side effect profile is primarily related to its mechanism of action (SGLT2 inhibition) which causes glycosuria, leading to genital infections and potential volume depletion, rather than gastrointestinal effects 3.

Comparison with Other SGLT2 Inhibitors

• Sotagliflozin, a dual SGLT1/SGLT2 inhibitor (not empagliflozin), has been associated with diarrhea in clinical trials, likely due to its SGLT1 inhibition in the intestines 2.
• In the SOLOIST-WHF trial, diarrhea was specifically noted as a common adverse effect with sotagliflozin but not with empagliflozin 2.
• Empagliflozin has greater selectivity for SGLT2 versus SGLT1 receptors compared to some other agents in this class, which may explain its lower association with gastrointestinal side effects 1.

Dose-Related Considerations

• A systematic review and meta-analysis comparing low-dose (10 mg) versus high-dose (25 mg) empagliflozin found no significant differences in overall adverse drug events between the two dosages 4.
• This meta-analysis did not identify diarrhea as a significant dose-dependent adverse effect of empagliflozin 4.

Known Side Effects of Empagliflozin

• The most commonly reported adverse effects of empagliflozin include:
  • Genital mycotic infections (more common in women) 3, 4
  • Urinary tract infections 4
  • Volume depletion (particularly in elderly patients or those on diuretics) 1, 5
  • Risk of euglycemic ketoacidosis 1, 5
• Empagliflozin has demonstrated cardiovascular and renal benefits in patients with type 2 diabetes, which may outweigh potential side effects in appropriate patients 3.

Clinical Implications

• When counseling patients about potential side effects of empagliflozin, focus should be on the more common adverse effects like genital infections and urinary tract infections rather than diarrhea 5, 4.
• If a patient on empagliflozin experiences diarrhea, consider other potential causes or concomitant medications rather than assuming it is directly caused by empagliflozin 3.
• For patients concerned about gastrointestinal side effects, empagliflozin may be a better choice compared to sotagliflozin or other medications known to cause diarrhea 2.

Special Considerations

• In patients with type 2 diabetes who have heart failure, empagliflozin has shown significant cardiovascular benefits without notable gastrointestinal adverse effects 2, 3.
• For patients with a history of gastrointestinal issues, empagliflozin may be preferable to other antidiabetic agents that are more commonly associated with diarrhea, such as metformin or GLP-1 receptor agonists 6, 7.

In conclusion, diarrhea is not a commonly reported side effect of empagliflozin based on clinical trial data and post-marketing surveillance. Patients and clinicians should focus on monitoring for the more typical side effects associated with SGLT2 inhibitors, particularly genital infections, urinary tract infections, and volume depletion.