This pilot clinical trial is designed to gather preliminary data on the efficacy and safety of empagliflozin, a diabetes drug in the sodium-glucose cotransporter 2 inhibitor (SGLT2i) class, in islet autotransplant recipients who have partial islet function.

Inclusion Criteria:

• Age 18-70 years old;
• >1 year after TPIAT date at enrollment;
• Partial islet function defined as stimulated C-peptide ≥0.6 ng/mL at screening/baseline visit, AND either (1) on insulin at ≤0.25 unit/kg/day OR (2) not on insulin but HbA1c >6.5%;
• Stable diabetes management defined by stable on pump or multiple daily injections (MDI) for at least 8 weeks and <25% change in insulin dosing over prior 8 weeks.
• Willing to manage diabetes medication management/dose adjustments for the duration of the study with study team MD
• Willing to wear continuous glucose monitor for diabetes management (currently standard of care for TPIAT diabetes)
• Willing to record insulin doses for 14 day intervals x 3 study visits.
• Willing and able to come to the UMN Clinical Research Unit for 3 study visits, approximately 3 months apart
• No prescribed medications other than insulin to treat diabetes in the past 4 weeks.

Exclusion Criteria:

• HbA1c >9%; on any non-insulin antihyperglycemic medication;
• History of diabetic ketoacidosis (DKA) in the past 1 year;
• Unable to drink Boost HP due to true milk protein allergy;
• Underweight (BMI <18.5 kg/m2) [contraindicated by possible weight loss with SGLT2 inhibitors];
• Renal failure defined by glomerular filtration rate <30 mL/min/m2;
• Recurrent dehydration necessitating ED/hospital visits; one time/ rare hospital visits due to intercurrent illness are not exclusionary but repeated dehydration from a chronic condition will be exclusionary.
• Expected to need systemic corticosteroids at >25 mg/day hydrocortisone equivalent over the 6-month study interval;
• Known allergy to empagliflozin;
• Currently pregnant or plan to become pregnant in the next 6 months (for females), or currently breastfeeding;
• Unwillingness to consent or return for study visits;
• Non-English speaking.
• Any other medical contraindication to treatment or study participation in the opinion of the investigator that would impact either patient's safety or their ability to complete the study.