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.

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, △CP (2hCP - FCP), and updated homeostatic model assessment of β-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 β-cell function in the SITA group, whereas the levels of 2hCP and △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 β-cell function and improve insulin sensitivity in LADA to some extent.

• Authors: Lin Yang, Huiying Liang, Xinyuan Liu, Xia Wang, Ying Cheng, Yunjuan Zhao, Lingjiao Liu, Gan Huang, Xiangbing Wang, Zhiguang Zhou
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 106 Issue 4 Pg. e1529-e1541 (03 25 2021) ISSN: 1945-7197 [Electronic] United States
• PMID: 33475138 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

Chemical References

• Dipeptidyl-Peptidase IV Inhibitors
• Hypoglycemic Agents
• Insulin
• Sitagliptin Phosphate

Topics

• Adult
• Diabetes Mellitus, Type 1 (drug therapy, physiopathology)
• Dipeptidyl-Peptidase IV Inhibitors (therapeutic use)
• Female
• Glucose Clamp Technique
• Humans
• Hypoglycemic Agents (therapeutic use)
• Insulin (therapeutic use)
• Insulin Resistance
• Insulin Secretion
• Insulin-Secreting Cells (physiology)
• Male
• Middle Aged
• Prospective Studies
• Sitagliptin Phosphate (therapeutic use)
• Treatment Outcome