Rate of Inpatient Hypoglycemia Following a 1:1 Dose Interchange Between Concentrated Insulin Glargine to Insulin Detemir.

BACKGROUND: Insulin remains a mainstay of treating hyperglycemia in an acute setting. Insulin glargine 300 units/mL (Toujeo, iGlar300) has a different pharmacokinetic profile than 100 units/mL basal insulins, such as insulin detemir (iDet100) and iGlar100. While conversion from iGlar300 to iGlar100 requires a 20% dose decrease, there is currently no recommended interchange from iGlar300 to iDet100. OBJECTIVE: Compare the incidence of hypoglycemia in patients who received a 1:1 unit interchange from home iGlar300 or iGlar100 to iDet100 while admitted. METHODS: A retrospective study was conducted to evaluate adults within a multi-site network admitted between May and December 2019. Patients were included if they received at least one dose of iDet100 following interchange from home iGlar300 or iGlar100. The primary endpoint was the incidence of hypoglycemic events following a 1:1 interchange of iGlar300 vs. iGlar100 to inpatient iDet100. Secondary outcomes include overall hypoglycemic events, time to hypoglycemia, and doses given before hypoglycemia. RESULTS: Of 615 patients, 394 received a 1:1 unit interchange to iDet100 (52 from iGlar300 and 342 from iGlar100). Incidence of hypoglycemic events was significantly higher in those with a 1:1 interchange from iGlar300 versus iGlar100 (36.5% vs. 18.7%, p = 0.007). Significant differences were observed in overall hypoglycemic events, time to hypoglycemia, and number of doses given before hypoglycemic event. CONCLUSION AND RELEVANCE: A 1:1 unit interchange from iGlar300 to iDet100 led to a higher incidence of hypoglycemic events compared to those interchanged from iGlar100. Dose reduction should be considered when transitioning from home iGlar300 to iDet100 in the inpatient setting.

Characterization of excitatory prostanoid receptors in the human umbilical artery in vitro.

1. 5-HT and the prostanoid TP receptor agonists, U46619 and I-BOP, constricted the human umbilical artery with pEC50 values of 7.3+/-0. 2, 6.7+/-0.1, and 7.3+/-0.2, respectively. The selective TP receptor antagonist, GR32191 (0.1 microM), shifted the concentration-effect curves to U46619 and I-BOP to the right, but had no effect on the response to 5-HT. 2. The natural prostaglandins, PGF2alpha and PGE2, caused concentration-dependent contraction with pEC50 values of 5.2+/-0.2 and 4.9+/-0.2, respectively. PGD2 was a partial agonist with a pEC50 of 5.24+/-0.03. GR32191 (0.1 microM) inhibited the responses to all of these compounds suggesting that they produce contraction by acting at TP receptors. 3. Sulprostone failed to elicit contraction in the human umbilical artery at concentrations up to 4.4 microM suggesting the absence of EP1 and EP3 receptors. Despite this, 17-phenyltrinor PGE2 and GR63799 both induced contraction at concentrations above 1 microM, but the effects were sensitive to GR32191 (0.1 microM). 4. Fluprostenol had no effect on the human umbilical artery at concentrations up to 17 microM suggesting the absence of FP receptors. Cloprostenol was ineffective in two tissues, but caused contraction in one tissue at the highest concentration tested (1.7 microM). However, this response was abolished in the presence of GR32191 (0.1 microM). 5. The effects of four TP receptor antagonists were assessed by global non-linear regression analysis. GR32191, SQ29548, SQ30741, and ICI192605 competitively inhibited responses to U46619 with pKb values of 8.0+/-0.1, 7.6+/-0.1, 7.0+/-0. 2 and 8.1+/-0.1, respectively. 6 These results suggest that the human umbilical artery functionally expresses TP receptors, but not EP1, EP2 or FP receptors.