Table 3.

Strategies to mitigate the adverse effects of SGLT2i and GLP1-RA

Adverse EffectsFrequencySeverityMitigating Strategies
SGLT2i
 Genital fungal infectionaLowKeep genital area dry and clean. Prophylactic topical treatment for fungal infection in high-risk patients
 Volume depletionaLowProactive dose reduction of diuretics in euvolemic patients. Hold SGLT2i when patients have nausea, vomiting, or diarrhea. Implement “Sick day protocol”
 UTIbLowUse with caution. Avoid in patients at high risk of recurrent UTI (e.g., indwelling foley catheter or self-catheterization)
 DKAcHighPatient education on early recognition and implement “STOP DKA” protocol (stop SGLT2i, test for ketones, maintain intake of fluid and carbohydrates, and use maintenance and supplemental insulin)
 AmputationbHighEncourage self-examination by patients or caregivers. Foot examination by health care provider at clinic visits. Temporarily hold SGLT2i when having an open wound or infection of the foot
 Bone fracturebHighCaution in patients with risk of fall. Monitor PTH and vitamin D
GLP-1 RA
 Nausea/vomiting/diarrheaaLowPatient education on symptom recognition. Start at low dose and slowly uptitrate over 2–4 wk
 Cholelithiasis and cholecystitisbHighPatient education on recognition of symptoms
 Acute pancreatitisdHighCaution in patients with history of pancreatitis
  • SGLT2i, sodium glucose co-transporter 2 inhibitor; GLP-1 RA, glucagon-like peptide 1 receptor agonist; UTI, urinary tract infection; DKA, diabetic ketoacidosis; PTH, parathyroid hormone.

  • a Commonly reported in multiple, large clinical trials.

  • b Increased risk reported in a single, large clinical trial.

  • c Increased risk reported in meta-analysis of clinical trials.

  • d Reported in small clinical trials or case series.