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It is increasingly evident that SGLT2 inhibitors (SGLT2i) provide benefits for both patients with diabetes and with heart disease, however these medications are under-prescribed. Over the last few years, an interdepartmental coalition at our hospital has led to several quality improvement projects aimed at increasing SGLT2i use. Our first project focused on increasing prescription of SGLT2i by outpatient cardiologists. Our cardiology department hired a nurse practitioner to review the cardiology patient panels and identify people who might benefit from SGLT2i therapy. She assessed the percent utilization of these drugs - by the end of 24 weeks, she had reviewed 1561 charts and had increased the percentage of patients on an SGLT2i from 9.4% to 10.9%. More importantly, she created a protocol for sending informational messages to providers whose patients were eligible for SGLT2i therapy. Our team also led a project to increase inpatient SGLT2i prescriptions, evaluate barriers to their use, and assess physician comfort with inpatient initiation of therapy. To assess physician comfort with prescribing SGLT2i, we surveyed cardiologists, endocrinologists, and hospitalists regarding prescribing habits and factors preventing SGLT2i inpatient prescription. The most common factors for preventing initiation of SGLT2i therapy included unfamiliarity with evidence for SGLT2i, preference of outpatient initiation, lack of inpatient availability, and cost. To assess whether formulary availability was a barrier to inpatient use, we queried our hospital’s EMR to find the number of inpatient SGLT2i prescriptions before and after dapagliflozin and canagliflozin were added to the hospital formulary. We discovered that adding SGLT2i to our hospital formulary resulted only in a modest increase in the number of SGLT2i prescriptions. Further work needs to be done to increase the utilization of these medications. Disclosure A.V.Rivera: None. X.A.Wang: None. M.Grodsky: None. S.Gandhi: None. F.Karaisz: None. Y.Lev: None.

Plant lipoxygenases oxygenate linoleic acid to produce 13(S)-hydroperoxy-9Z,11E-octadecadienoic acid (13(S)-HPOD) or 9-hydroperoxy-10E,12Z-octadecadienoic acid (9(S)-HPOD). The manner in which these enzymes bind substrates and the mechanisms by which they control regiospecificity are uncertain. Hornung et al. (Proc. Natl. Acad. Sci. USA 96 (1999) 4192–4197) have identified an important residue, corresponding to phe-557 in soybean lipoxygenase-1 (SBLO-1). These authors proposed that large residues in this position favored binding of linoleate with the carboxylate group near the surface of the enzyme (tail-first binding), resulting in formation of 13(S)-HPOD. They also proposed that smaller residues in this position facilitate binding of linoleate in a head-first manner with its carboxylate group interacting with a conserved arginine residue (arg-707 in SBLO-1), which leads to 9(S)-HPOD. In the present work, we have tested these proposals on SBLO-1. The F557V mutant produced 33% 9-HPOD (S:R = 87:13) from linoleic acid at pH 7.5, compared with 8% for the wild-type enzyme and 12% with the F557V,R707L double mutant. Experiments with 11(S)-deuteriolinoleic acid indicated that the 9(S)-HPOD produced by the F557V mutant involves removal of hydrogen from the pro-R position on C-11 of linoleic acid, as expected if 9(S)-HPOD results from binding in an orientation that is inverted relative to that leading to 13(S)-HPOD. The product distributions obtained by oxygenation of 10Z,13Z-nonadecadienoic acid and arachidonic acid by the F557V mutant support the hypothesis that ω6 oxygenation results from tail-first binding and ω10 oxygenation from head-first binding. The results demonstrate that the regiospecificity of SBLO-1 can be altered by a mutation that facilitates an alternative mode of substrate binding and adds to the body of evidence that 13(S)-HPOD arises from tail-first binding.