Twenty-Four Hour Action of Insulin Glargine (Lantus) May Be too Short for Once-Daily Dosing: A case report

The insulin analog insulin glargine has a pharmacodynamic profile described as peakless and of longer duration than human NPH insulin (1). This allows for convenient once-daily dosing for coverage of basal insulin needs. We recently had the opportunity to examine whether this is the case in the following patient.

T.L. is a 53-year-old man with a history of type 1 diabetes for the past 16 years. Before hospitalization, he had a history of widely variable blood glucose levels, from 50 to 400 mg/dl, while using a 4-injection regimen of premeal insulin lispro and ultralente at dinner. He has no known diabetic complications. Before admission, he had a history of heavy ethanol abuse, with a daily intake of 48–72 oz wine or beer per day. On the day of admission, the patient developed left arm weakness and progressive loss of consciousness. A computed tomography scan revealed a massive intracerebral bleed. Admission laboratory data revealed glucose of 292 mg/dl, a bicarbonate of 15 mEq/l, an anion gap of 18, trace urine ketones, and a blood pH of 7.34. After treatment of compensated diabetic ketoacidosis, the patient was maintained on an intravenous insulin infusion between 1 and 2 units/h. On the fifth hospital day, enteral feedings via a feeding tube were initiated. The enteral formula provided 2 kcal/ml, with a composition consisting of 43% carbohydrate, 17% protein, and 40% fat. The feeding rate was successfully increased and maintained at 35 ml (70 calories) per hour without residual stomach accumulation. Total nutrition intake was 1,680 kcal/day. On the sixth hospital day, the patient was given a 30-unit dose of insulin glargine at 9:00 p.m. and was weaned off of the insulin infusion over the next 4 h. For the next 11 days, the patient continued to receive continuous enteral feeding. He remained on respiratory support and received no other calories by either oral or parenteral route. From day 6 to day 12, he received insulin glargine as a single dose, given at 9:00 p.m. In addition to basal insulin coverage, as described above, glucose excursions >200 mg/dl were treated with supplemental subcutaneous lispro insulin. Marked hyperglycemia was noted at 10:00 p.m. after this single-dose regimen and required supplemental lispro insulin coverage on 4 of the 6 days. For purposes of comparison, days 7–12 are defined as period 1. For days 13–18, or period 2, the glargine dose was converted to a split dose given at 9:00 a.m and 9:00 p.m. On day 13, the patient’s enteral tube feeding was electively discontinued from 11:00 a.m to 2:00 p.m. for a procedure. At 2:00 p.m., hypoglycemia occurred (blood glucose 41 mg/dl). Two subsequent glargine doses were held and then restarted at 10 units every 12 h. The mean glucose levels were not significantly different between the two treatment periods during time points 2:00 a.m, 6:00 a.m, 10:00 a.m, 2:00 p.m., and 6:00 p.m. However, the mean glucose level was significantly higher at 10:00 p.m. during period 1 than at 10:00 p.m. during period 2 (mean glucose 226 ± 37 vs. 132 ± 27 mg/dl, respectively, P < 0.005 by two-tailed t test). This data point represents 1-h postdosing, or 25 h after receiving the previous dose.

The data suggest that, in this patient, insulin glargine has a 24-h action profile. However, the slow onset of action for the subsequent nighttime dose may have produced a window of relative insulinopenia, resulting in higher blood glucose levels at night. This problem was corrected by giving glargine as a split dose every 12 h. We suggest that for patients receiving a constant inflow of carbohydrates, once-daily dosing of insulin glargine may not provide effective 24-h coverage. In addition, the present case underscores the need to provide intravenous dextrose to glargine-treated patients receiving continuous enteral feeding in the event that the enteral feeding is discontinued. We suggest that more studies are needed to determine whether once-daily dosing of insulin glargine provides effective basal insulin coverage for all insulinopenic patients in various clinical settings or whether a subset of patients may require twice-daily dosing.