OBJECTIVE: To examine the influence of baseline U-100 insulin @entity2794 ( @entity2794 ) on clinical outcomes in severely insulin-resistant @entity1 with inadequately controlled type 2 @entity6 treated with @entity1 regular U-500 insulin (U-500R) from the perspective of current dosing recommendations. METHODS: Data from a recent prospective, randomized @entity2794 ( @entity2794 ) and twice-daily (BID) U-500R in 325 @entity1 transitioned from high-dose/high-volume U-100 insulin were analyzed across baseline U-100 @entity2794 units and units/kg subgroups ( <=300 units [n = 224, 68.9%] and >300 units [n = 101, 31.1%];  <=2 units/kg [n = 96, 29.5%] and >2 units/kg [n = 229, 70.5%]). Subgroup effects on treatment differences were evaluated, and outcomes between treatment-pooled subgroups were compared. RESULTS: At 24 weeks, significant reduction in glycated hemoglobin (HbA1c) was observed for all subgroups (range: -1.01% to -1.38%, P < .05). Within-subgroup treatment effects were similar with no treatment-by-subgroup interactions; however, greater reduction was noted in the >300-units subgroup (P = .04). No @entity2794 /BID differences within subgroups or treatment-by-subgroup interactions were observed for @entity2794 or weight increase from baseline. Overall @entity4053 rates were similar between treatments (within subgroups) and showed no interactions. However, rates were higher in the >300-units subgroup for severe @entity4053 (P = .04) and in both higher-dose subgroups for documented symptomatic @entity4053  <=70 mg/dL (P < .001, units; P = .001, units/kg). CONCLUSION: Both @entity2794 and BID U-500R were efficacious and safe across @entity2794 subgroups, though higher @entity4053 rates were observed in higher-dose, treatment-pooled subgroups. Accordingly, U-500R dosing recommendations have been updated.

EFFECT OF TOTAL DAILY DOSE ON EFFICACY, DOSING, AND SAFETY OF 2 DOSE TITRATION REGIMENS OF @entity1 REGULAR U-500 INSULIN IN SEVERELY INSULIN-RESISTANT XXXX WITH TYPE 2 DIABETES.

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity2794 :: ('MESH:D020773', 'Disease') :: ['total daily dose', 'trial comparing thrice-daily', 'TID', 'TDD'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetes'] @entity4053 :: ('MESH:D007003', 'Disease') :: ['hypoglycemia']
@entity1 :: (9606,Species) :: ['PATIENTS']
