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This result is partly due to the higher (4.4 vs. 4.0 mmol/L) 5% maximum hypoglycemic risk threshold specified at these intervals (Table 2).
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Modern insulin analogs were designed to achieve improved blood glucose control with similar hypoglycemic risk compared with non-analog insulins (or similar blood glucose control with reduced hypoglycemic risk).
These rationally-designed partial agonists provide an approach to interrogate whether control of maximal activity can provide glycemic control with reduced hypoglycemic risk.
The controller is provided with a feedforward loop to improve meal compensation, a gain scheduling scheme to improve the controller performance in controlling the nonlinear glucose insulin system, and an asymmetric cost function to reduce the hypoglycemic risk.
The incretins have the advantage of an extremely low hypoglycemic risk when used as monotherapy.
Liraglutide's glucose-lowering action is strictly glucose dependent with low hypoglycemic risk.
The hypoglycemia experience supports the potential for dapagliflozin to achieve meaningful glycemic efficacy with relatively low hypoglycemic risk.
These programs have been successfully delivered in other settings (103, 104) with comparable reductions in hypoglycemic risk (105).
For example, exenatide has a 5% hypoglycemic risk as a monotherapy, which increases to 35% when combined with a sulfonylurea.
The main benefit of such a combination would be reducing hypoglycemic risk whenever targeting an A1C level of <7.0%.
Based on this Kalman state estimate, the hypoglycemic module computes a 30-min prediction of hypoglycemic risk and downmodulates insulin delivery according to a patient-specific inverse proportionality (13).
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