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Abstract

Objective: Peripheral insulin resistance in type 1 diabetes may be related to a paradoxical postprandial glucagon increase. This study evaluated the effects of sitagliptin, (DPP-IV inhibitor, approved for patients with type 2 diabetes), in adults with type 1 diabetes to improve glycemic control through decreasing postprandial glucagon.Methods This investigator-initiated, double-blind, randomized-parallel 20-week study enrolled 141 subjects. Subjects received sitagliptin 100 mg/day or placebo for 16-weeks. A subset of 85 patients wore blinded continuous glucose monitors (CGM) for 5 separate 7-day periods. The primary outcome was post-meal (Boost™) reduction in 4-hour glucagon area under the curve (AUC). Secondary endpoints included changes in A1c, CGM data, insulin dose, GLP-1, GIP, and C-peptide levels.Results There were no differences at screening between groups; however, after 4-week run-in phase, A1c was significantly lower in the sitagliptin vs. placebo group. Post-meal GLP-1 levels were higher (P<0.001) and GIP levels lower (P=0.03), with glucagon suppression at 30 minutes (LS means 23.2 ± 1.9 vs. 16.0 ± 1.8, P=0.006) in the sitagliptin group at 16-weeks. There were no differences between the groups in change in A1c, insulin dose, weight, or C-peptide after 16-weeks of treatment. However, C-peptide positive patients randomized to sitagliplin had a non-significant trend toward decrease in A1c, mean glucose and time spent in hyperglycemia.Conclusion Sitagliptin use in type 1 diabetes did not change glucagon AUC, A1c, insulin dose or weight despite post-meal rise in GLP-1 levels. C-peptide positive subjects treated with sitagliptin had a non-significant trend in decreasing hyperglycemia which needs further evaluation.