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Introduction
Type 2 diabetes is characterized by hyperglycemia and is associated with a high risk of cardiovascular, microvascular, and other complications; it is a heterogeneous disease involving pancreatic β-cell dysfunction and insulin resistance [1, 2]. A progressive decline in β-cell function decreases insulin secretion and disrupts glucose homeostasis [3, 4–5].
Glucagon-like peptide-1 (GLP-1), a peptide produced in the entero-endocrine L-intestinal cells, is a major incretin hormone that stimulates insulin secretion after nutrient ingestion. Owing to its involvement in pancreatic β-cell proliferation and survival and the regulation of glucagon secretion, food intake, and gastric and intestinal motility, it has helped develop efficient pharmacologic treatments for diabetes and obesity [6, 7].
Several GLP-1 receptor agonists (GLP-1ras) with distinct structural and pharmacokinetic properties are currently used to treat type 2 diabetes and to prevent cardiovascular disease, the main cause of death in patients with type 2 diabetes. These agonists improve glycemic regulation with a low risk of hypoglycemia and weight reduction. Furthermore, recent trials on cardiovascular outcomes have reported that GLP-1ras liraglutide and semaglutide reduce the occurrence rate of cardiovascular events and deaths among patients with type 2 diabetes at high cardiovascular risk [8, 9].
However, some clinical trials have reported that the glucose-lowering effect of GLP-1ras potentially differs among individuals, with some patients exhibiting insufficient responses in the clinical setting. Accordingly, predictors of the therapeutic response to GLP-1ra are needed to identify patient subsets potentially benefiting from GLP-1ras treatment. We hypothesized that residual insulin secretory capacity in patients with type 2 diabetes is an important predictor of the glucose-lowering effect of GLP-1ra. Hence, the present study aimed to identify factors predicting the efficacy of GLP1ras on Hemoglobin A1c (HbA1c) in patients with insulin-independent diabetes. Furthermore, since GLP1-ra promotes weight loss, along with glucose-lowering effects, we evaluated the association between residual β-cell function and weight loss effects of GLP-1ra.
Methods
Study Design and Ethics
This retrospective, single-center study was conducted at Kanazawa University Hospital between November 2010 and June 2014. All procedures were performed in accordance with the 1964 Helsinki Declaration and its later amendments. The study was approved by the ethics committees at the University of Kanazawa (no. 2014124), and patient consent was waived by the ethics committee owing to the retrospective nature of the study. Since...