Sitagliptin as add-on therapy in insulin deficiency: biomarkers of therapeutic efficacy respond differently in type 1 and type 2 diabetes

Ottavio Giampietro, Chiara Giampietro, Luca Della Bartola, Maria Chiara Masoni, Elena Matteucci

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Background: Sitagliptin has been proven to be effective and safe as add-on to insulin in adult patients with type 2 diabetes and absolute insulin deficiency. Recently, it has been suggested to extend the use of dipeptidyl-peptidase-4 inhibitors to type 1 diabetes. The aim of this study was to evaluate and compare the effects of a long-term, fixed-dose combination of sitagliptin and metformin as add-on to insulin on body mass index, fasting plasma glucose, fructosamine, HbA_1c, lipids, and daily dose of insulin in both type 1 diabetes and insulin-treated type 2 diabetes.
Methods: We recruited 25 patients with type 1 diabetes (mean age 51 ± 10 years, mean disease duration 26 ± 13 years) and 31 insulin-treated type 2 diabetic patients (mean age 66 ± 8 years, mean disease duration 19 ± 9 years), who received sitagliptin with metformin as a fixed-dose combination (50/1000 mg once or twice daily) or sitagliptin (100 mg once daily, if intolerant to metformin) in addition to ongoing insulin therapy for 46 ± 19 weeks and 56 ± 14 weeks, respectively.
Results: After 21 ± 9 weeks, patients with type 1 diabetes had a significantly lower body mass index, fasting plasma glucose, fructosamine, HbA_1c, and daily insulin requirement. After 49 ± 17 weeks, they maintained their weight loss and total daily insulin dose and showed a significant reduction in low-density lipoprotein cholesterol levels, whereas their HbA_1c had returned to baseline values. In patients with type 2 diabetes, long-term treatment remained weight-neutral but had persistent beneficial effects on short-term, intermediate-term, and long-term biomarkers of metabolic control, as well as on low-density lipoprotein cholesterol levels and insulin requirement.
Conclusion: Clinical outcomes differed according to type of diabetes in terms of quality and over time. In type 2 diabetes, the combination therapy significantly improved metabolic control and the lipid profile, and decreased insulin requirements, even in the absence of clinically significant weight loss. In type 1 diabetes, the combined therapy only temporarily improved metabolic control, but significantly decreased body weight, low-density lipoprotein cholesterol levels, and insulin requirements.

Keywords: dipeptidyl-peptidase-4 inhibitors, drug therapy combination, metformin, synthetic analogs of insulin, diabetes mellitus, type 1, type 2