Islet Function and Insulin Sensitivity in Latent Autoimmune Diabetes in Adults Taking Sitagliptin: A Randomized Trial

Context: The long-term effects of dipeptidyl peptidase-4 inhibitors on beta-cell function and insulin sensitivity in latent autoimmune diabetes in adults (LADA) are unclear. Objective: To investigate the effects of sitagliptin on beta-cell function and insulin sensitivity in LADA patients receiving insulin. Design and Setting: A randomized controlled trial at the Second Xiangya Hospital. Methods: Fifty-one patients with LADA were randomized to sitagliptin + insulin (SITA) group or insulin alone (CONT) group for 24 months. Main Outcome Measures: Fasting C-peptide (FCP), 2-hour postprandial C-peptide (2hCP) during mixed-meal tolerance test, Delta CP (2hCP - FCP), and updated homeostatic model assessment of beta-cell function (HOMA2-B) were determined every 6 months. In 12 subjects, hyperglycemic clamp and hyperinsulinemic euglycemic clamp (HEC) tests were further conducted at 12-month intervals. Results: During the 24-month follow-up, there were no significant changes in beta-cell function in the SITA group, whereas the levels of 2hCP and Delta CP in the CONT group were reduced at 24 months. Meanwhile, the changes in HOMA2-B from baseline were larger in the SITA group than in the CONT group. At 24 months, first-phase insulin secretion was improved in the SITA group by hyperglycemia clamp, which was higher than in the CONT group (P <.001), while glucose metabolized (M), insulin sensitivity index, and M over logarithmical insulin ratio in HEC were increased in the SITA group (all P <.01 vs baseline), which were higher than in the CONT group. Conclusion: Compared with insulin intervention alone, sitagliptin plus insulin treatment appeared to maintain beta-cell function and improve insulin sensitivity in LADA to some extent.

Automated summary

The study findings suggest that compared with insulin intervention alone, sitagliptin plus insulin treatment appears to maintain beta-cell function and improve insulin sensitivity in LADA patients to some extent.