CHICAGO – Once-daily oral sitagliptin appears to be safe and effective for the management of hyperglycemia in patients with type 2 diabetes hospitalized on general medicine or surgery wards, according to an industry-sponsored pilot study.
"Our results suggest that many hospitalized patients with type 2 diabetes could be treated with sitagliptin plus corrective rapid-acting insulin as needed. Patients with persistent hyperglycemia can be treated with sitagliptin and a low dose of glargine once daily or with basal-bolus insulin," Dr. Roma Gianchandani said at the annual scientific sessions of the American Diabetes Association.
Sitagliptin (Januvia) is an attractive alternative to current guideline-recommended basal-bolus insulin regimens, which are labor intensive, require multiple daily injections, and entail a significant risk of hypoglycemia, said Dr. Gianchandani of the University of Michigan, Ann Arbor.
Dr. Roma Gianchandani
She presented a randomized, open-label study of 82 noncritically ill patients with type 2 diabetes hospitalized on general medicine or surgery wards. Their mean hospital length of stay was 6.5 days. Because there have been no previous studies on the use of a dipeptidyl peptidase–4 (DPP-4) inhibitor such as sitagliptin in this context, entry criteria were stringent. Patients were enrolled if they had early-stage type 2 diabetes as reflected in a prehospital treatment regimen involving diet and oral antidiabetic agents or a low total daily insulin dose of up to 0.4 units/kg per day.
Participants were randomized to one of three treatment arms: sitagliptin at 100 mg once daily provided their creatinine clearance exceeded 50 mL/min, or 50 mg/day if their creatinine clearance was 30-50 mL/min; sitagliptin plus once-daily insulin glargine at 0.2 units/kg per day if their admission blood glucose value was 140-200 mg/dL, and glargine at 0.25 units/kg per day if it was 201-400 mg/dL; or a standard basal-bolus insulin regimen at a total daily insulin dose of 0.44 units/kg per day if their admission blood glucose was 140-200 mg/dL and 0.5 units/kg per day if it was 201-400 mg/dL. In the basal-bolus group, half of the total daily dose was given as glargine once daily and half as lispro in three equal doses before meals or every 6 hours.
Patients in all three study arms received a supplemental dose of lispro before meals if their premeal blood glucose exceeded 140 mg/dL.
A key study finding was that glycemic control improved similarly in all three study groups. After the first day of treatment there were no significant differences in mean daily blood glucose. Nor did the percentage of blood glucose readings falling within the target range of 70-140 mg/dL differ significantly: It was 36% in the sitagliptin-only group and 43% in the other two treatment arms. The percentage of blood glucose readings above the cutoffs of 140 and 200 mg/dL was likewise similar in all three treatment groups. The rate of treatment failure, defined as three or more consecutive blood glucose readings greater than 240 mg/dL or a mean daily blood glucose above that level, was 11% in the sitagliptin-alone group, 10% with sitagliptin plus basal insulin, and 8% with basal-bolus therapy.
The rate of hypoglycemia below 70 mg/dL was statistically similar in all three groups: 4% with sitagliptin alone, 7% with sitagliptin and basal insulin, and 8% with basal-bolus insulin.
Patients in the sitagliptin group averaged 1.8 insulin injections per day after day 1 of their hospital stay, significantly less than the 2.5 per day in the basal-bolus therapy group. Patients on sitagliptin plus basal insulin averaged 1.3 injections per day. Total insulin per day averaged 11.5 units in the sitagliptin group, 28.2 units in the sitagliptin plus basal insulin–treated patients, and 39.6 units in the basal-bolus group.
There were no between-group differences in complication rates or length of stay, Dr. Gianchandani continued.
One audience member said the generalizability of the study findings is limited by the small number of patients and stringent entry criteria. He estimated that 80% of his own type 2 diabetic patients hospitalized on general medicine or surgery wards wouldn’t have qualified for the trial.
Dr. Gianchandani responded that based on the favorable results of this pilot study, a larger study with a broader range of patients is being planned.
Another audience member, Dr. Stanley Schwartz of Ardmore, Pa., rose to enthusiastically declare, "I think this is actually a seminal study." He noted that nearly half of the patients in the sitagliptin-alone group never required any supplemental insulin injections during their hospital stay.
"Think about it: 40%-50% of these patients with early diabetes who may have otherwise required low doses of insulin didn’t need insulin because they were on sitagliptin alone. I think this is a superb study and should be pursued further," he said.