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

Abstract

Context The long-term effects of dipeptidyl peptidase-4 inhibitors on β-cell function and insulin sensitivity in latent autoimmune diabetes in adults (LADA) are unclear. Objective To investigate the effects of sitagliptin on β-cell function and insulin sensitivity in LADA patients receiving insulin. Design and Setting A randomized controlled trial at the Second Xiangya Hospital. Patients and Interventions Fifty-one patients with LADA were randomized to sitagliptin + insulin group (SITA group) or insulin alone group (CONT group) for 24 months. Main Outcome Measures Fasting C-peptide (FCP), 2-hour postprandial C-peptide (2hCP) during mixed-meal tolerance test, △CP (2hCP - FCP) and updated homeostatic model assessment of β-cell function (HOMA2-B) were deterrmined 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 β-cell function in SITA group, whereas the levels of 2hCP and △CP in CONT group were reduced at 24 months. Meanwhile, the changes in HOMA2-B from baseline were larger in SITA group than in CONT group. At 24 months, first-phase insulin secretion was improved in SITA group by hyperglycemia clamp, which was higher than in CONT group (P<0.001), while glucose metabolized(M), insulin sensitivity index and M over logarithmical insulin ratio in HEC were increased in SITA group (all P<0.01 vs. baseline), which were higher than in CONT group. Conclusions Compared with insulin intervention alone, sitagliptin plus insulin treatment appeared to maintain β-cell function and improve insulin sensitivity in LADA to some extent.

Efficacy and safety of sitagliptin and insulin for latent autoimmune diabetes in adults: A systematic review and meta‐analysis

“…Of the remaining 188 articles, 180 articles were excluded by reading the full texts, of which four had no useful outcomes, 166 were not related to sitagliptin or LADA and 10 were non‐RCTs. Finally, eight eligible trials 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 involving 295 participants that met our inclusion criteria were included in the present study. The flowchart of the study selection process is summarized in Figure 1 .…”

Dipeptidyl Peptidase 4 (DPP4) as A Novel Adipokine: Role in Metabolism and Fat Homeostasis

“…Sitagliptin had no effect on β cell function in individuals with long-standing T1DM [ 90 ], but it improved β cell functionality [ 91 , 92 ] and insulin sensitivity in subjects with LADA [ 91 ], inducing changes of T cell phenotype and gene expression profile [ 93 ]; indeed, DPP4-I treatment is nowadays considered as a therapeutic option in LADA subjects [ 36 ].…”

Latent autoimmune diabetes in adults in China

“…Dipeptidyl peptidase-4 inhibitor (DPP-4i) can inactivate the DPP-4 enzyme, lead to an increase in the level of GLP-1, promote insulin secretion from pancreatic β-cells, and lead to lower blood glucose A randomized controlled trial in a Chinese population found that insulin plus sitagliptin outperformed insulin alone to maintain C-peptide level ( 65 , 67 ). Other studies involving the Caucasian population studies have also reported similar benefits of saxagliptin ( 68 , 69 ) and linagliptin ( 70 ).…”