*Purpose: Insulin therapy is commonly prescribed to treat hyperglycemia early post-kidney transplant (KTx) due to its widespread availability and ease of titration. Alternatively, there is limited evidence analyzing the comparative effectiveness of oral therapies on glycemic outcomes following KTx.

*Methods: This was a single-center, retrospective cohort study of adult KTx recipients with new or worsening hyperglycemia requiring treatment between 01/2014-05/2020. Patients were excluded if they had received a prior or combined organ transplant, had a history of type 1 diabetes or HIV, were converted to belatacept, or were on intensive insulin prior to transplant. Patients discharged on oral medications were matched in a 1:1 ratio to patients receiving intensive insulin based on pre-transplant diabetes regimen, baseline hemoglobin A1c (HbA1c), duration of diabetes, and steroid maintenance. The primary endpoint was the number of hyperglycemia-related readmissions within 6 months of KTx. Key secondary endpoints included HbA1c at 6 months post-transplant, serum glucose levels and documented hypoglycemia within 1 month of KTx, and treated urinary or bloodstream infections.

*Results: 30 patients prescribed intensive insulin were matched to 30 patients receiving oral therapies based on clinical parameters. Four patients in each group were discharged on chronic steroid therapy, while others received dual tacrolimus and mycophenolate. Baseline characteristics were similar between groups, with the exception of more Caucasians in the insulin group (53.5% vs 26.7%; p=0.04). There were no differences between groups in the incidence of the primary endpoint (3.3% vs 6.7%; p=0.55) or all-cause readmissions within 30 days (26.7% vs 26.7%; p=1.00); however, 9 patients in the oral group required the use of emergency sliding scale insulin and 7 (23.3%) subsequently were converted to standing insulin. HbA1c at 6 months was similar between groups (7.0 vs 7.3; p=0.49), and no differences were observed in serum glucose levels during follow-up (179.9 vs 179.8; p=0.99). There were also no significant differences in the incidence of laboratory reported hypoglycemia or weight change at 6 months. More insulin patients were treated for urinary or bloodstream infections, however this did not reach statistical significance (23.3% vs 13.3%; p=0.32).

*Conclusions: This study suggests that the early use of oral antiglycemics post-KTx in selected patients results in similar outcomes relative to insulin therapy. Rigorous follow-up of blood glucose levels is still required, as up to 25% of patients may require conversion to intensive insulin within the first month. Practitioners should consider concomitant comorbidities, lifestyle preferences, and patient goals of care when selecting patients for oral therapies.

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