Comparative Effectiveness of SGLT2i and DPP-4i in T2D

The study population included patients 18 years and older who initiated treatment with a SGLT2i (canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin) or a DPP-4i (alogliptin, saxagliptin, linagliptin, or sitagliptin) between April 1, 2013 (consistent with the US Food and Drug Administration [FDA] approval of the first SGLT2i), and June 30, 2021. Treatment with DPP-4i was selected as the comparator because these medications are also frequently used as second-line therapy for T2D, have similar out-of-pocket costs as SGLT2i but a different mechanism of action, which does not involve inhibition of kidney glucose reabsorption and osmotic diuresis, and have shown no association with atherosclerotic cardiovascular outcomes. Cohort entry was the day of the first filled prescription of either SGLT2i or DPP-4i, with no use in the previous 6 months. Study eligibility was limited to patients with at least 6 months of continuous health plan enrollment, a recorded T2D diagnosis before cohort entry, and at least 1 HbA_1c laboratory result recorded within 3 months before cohort entry. We excluded patients with records of type 1, secondary, or gestational diabetes; malignant neoplasms; end-stage kidney disease; kidney replacement therapy; no laboratory results for creatinine; or nursing home residence within 6 months preceding cohort entry (eFigure 1 and eTable 2 in Supplement 1). Based on the most recent HbA_1c baseline value, we identified 3 different subcohorts which comprised patients with controlled (HbA_1c <7.5%), above-target (HbA_1c 7.5%-9%), or elevated (HbA_1c >9%) glycemia, respectively (to convert percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01). The cutoffs for HbA_1c stratification were chosen by both inspecting terciles of the HbA_1c distribution among SGLT2i treatment initiators and considering the thresholds currently recommended to define controlled vs uncontrolled hyperglycemia.^{12 (link),13 (link)}