PROLONGED EFFICACY OF SHORT-ACTING INSULIN LISPRO COMBINATION WITH HUMAN ULTRALENTE IN INSULIN-DEPENDENT DIABETES-MELLITUS

Insulin Lispro is a newly FDA approved analog of human insulin that ex hibits rapid absorption and a short duration of action after sc inject ion. Although Lispro insulin improves immediate postprandial glycemia compared to Regular insulin, long term trials of Lispro insulin have n ot shown improvement in overall glycemic control, as determined by gly cosylated hemoglobin. We hypothesize that this lack of improvement is attributable to the development of late postprandial hyperglycemia sec ondary to a waning of Lispro insulin's effect in conjunction with cont inued meal absorption. This study was designed to evaluate the duratio n of Lispro-induced reductions in plasma glucose after a standardized meal when Lispro insulin is incorporated into a regimen typically empl oyed in insulin-dependent diabetes mellitus. After establishment of eu glycemia overnight, 12 healthy IDDM patients received human Ultralente insulin (0.2 U/kg) alone and in combination with each of the followin g treatments in random sequence immediately before ingesting a 750-Cal American Diabetes Association breakfast: 1) 0.15 U/kg human Regular i nsulin (Regular 0.15 group), 2) 0.15 U/kg Lispro insulin (Lispro 0.15 group), 3) 0.1 U/kg Lispro insulin (Lispro 0.1 group), and 4) an equim olar (1:1) mixture of Lispro and Regular insulins (0.15 U/kg; 1:1 Mix group). Glucose and hormonal parameters were assessed for 8 h after th e meal. Peak postprandial glucose was increased in the Regular insulin group compared to that in all groups that incorporated Lispro insulin (P < 0.001). Glucose area under the curve (AUG) was decreased in the Lispro 0.15 group compared to that in the Lispro 0.1 group, and glucos e AUC was decreased in the Lispro 0.15 and 1:1 Mix groups compared to that in the group given Regular insulin (P < 0.001). Mean plasma gluco se concentrations during the final hour of study were increased in the Ultralente group compared with those in all other treatment groups an d were increased in the Lispro 0.1 group compared with those in the Re gular, Lispro 0.15, and 1:1 Mix groups (P < 0.05). Insulin AUC was sig nificantly reduced in the Lispro 0.1 group compared to those in all ot her short acting insulin groups (P < 0.001), and time to peak insulin was more rapid in the two Lispro groups than those in all other treatm ent groups (P < 0.01). The glucagon response was significantly greater in the Ultralente group compared to those with all other treatments. There was no difference in the development of hypoglycemia between the groups. This study demonstrates that the reductions in plasma glucose effected by Lispro insulin are consistent and stable for 8 h after me al ingestion when Lispro insulin is used in combination with human Ult ralente insulin. These findings suggest that improvement in overall gl ycemia, as assessed by glycosylated hemoglobin, may be achievable with Lispro insulin if adequate doses are administered.