TABLE 2.
Considerations for Initiation of SGLT2 Inhibitor Therapy
| STICH (20) | International Consensus (18) | STOP DKA (19) | Anne L. Peters’ Protocol (14) | EMA Guidance (11,12) | NICE Guidance (21–23) | |
|---|---|---|---|---|---|---|
| Dosing | NA | • Initiate at lowest dose possible | Prescribe lower doses of SGLT2i | • Start SGLT2i in the morning, after ketone testing; do not take if BHB ≥6 mmol/L or urine has more than trace ketones | • Dapagliflozin 5 mg/day | Dapagliflozin: 5 mg/day |
| • Some HCPs even suggest splitting doses | • Start with one-fourth to one-half tablet of the lowest dose | • Sotagliflozin 200 mg/day before first meal of day; may be increased after 3 months to two tablets (400 mg/day) | ||||
| • Increase dose slowly every 2 weeks based on blood ketone levels | ||||||
| Maximum dosage | NA | NA | NA | • Canagliflozin: 100 mg/day | • Dapagliflozin: 5 mg/day | NA |
| • Empagliflozin: 10 mg/day | • Sotagliflozin: 400 mg/day | |||||
| • Dapagliflozin: 5 mg/day | ||||||
| • Ertugliflozin: 5 mg/day | ||||||
| Ketone monitoring before SGLT2i initiation | NA | NA | NA | • Measure daily fasting ketones for 2 weeks; report values to clinician weekly | Obtain several baseline ketones over 1–2 weeks before SGLT2i initiation | NA |
| • Continue monitoring until stable on maximum dose for 2 weeks; once on stable dose of SGLT2i, monitor as needed routinely | ||||||
| Timing of insulin adjustment | During initiation and maintenance | At least every 24–48 hours initially | • During initial phase of SGLT2i use | Do not adjust insulin in advance or initially | • Adjust mealtime insulin with first dose | NA |
| • Reassess once patient is stabilized on SGLT2i | • No reduction in basal insulin when initiating SGLT2i | |||||
| Adjustments in insulin dosage | • Clinicians should carefully monitor insulin dose reductions | • If switching insulin (injection to pump; manual to automatic delivery), hold SGLT2i until insulin doses are adjusted and blood glucose and ketones are normal | • Insulin doses cautiously adjusted | • Clinicians should discuss that less premeal insulin may be required subsequently | • 20% reduction in first mealtime bolus insulin may be considered with first dose of dapagliflozin/sotagliflozin | • During treatment with dapagliflozin, insulin therapy should be continuously optimized to prevent ketosis and DKA |
| • Clinicians need to individualize dose reductions | • Basal insulin doses modified based on blood glucose values | • Adjust dose using correction factor and insulin-to-carbohydrate ratio | • No initial reduction in basal insulin is recommended | • Insulin dose should only be reduced to avoid hypoglycemia | ||
| • If glycemia is relatively well controlled (A1C <7.5%), 10–20% reduction in insulin doses | • Try to avoid insulin dose reductions of >20% | • Adjust insulin based on CGM when possible | • Subsequently, basal insulin should be adjusted based on blood glucose results | |||
| • If glycemia is less well controlled (A1C ≥7.5%), slight or no reductions in prandial and basal insulin | • Never stop insulin |
NA, not applicable; SGLT2i, SGLT2 inhibitor.