ArticlesEffect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and β-cell function in type 2 diabetes: a parallel-group study
Introduction
Type 2 diabetes is characterised by insulin resistance and β-cell dysfunction.1 It results in deterioration of glycaemic control over time, primarily through progressive β-cell dysfunction.1 Although strict glycaemic control reduces the risk of microvascular complications, the deterioration of β-cell function seems inevitable.1, 2
Glucagon-like peptide 1 (GLP-1) is an intestinally produced peptide hormone. Under physiological conditions, it is secreted in response to ingestion of food3 and has an important role in regulating postprandial blood glucose concentrations.4 GLP-1 secretion is lower than normal in patients with type 2 diabetes,5 which suggests that the hormone may contribute to the pathogenesis of the disease. Exogenous GLP-1 acutely stimulates insulin secretion, inhibits glucagon secretion, and lowers plasma glucose concentrations in people with type 2 diabetes.6 In addition, GLP-1 inhibits gastric emptying7 and reduces appetite in these patients.8 In rats, GLP-1 reverses age-dependent decline in β-cell function9 and stimulates β-cell proliferation and neogenesis.10 Thus, GLP-1 may be useful in the treatment of type 2 diabetes. This study was undertaken to investigate the long-term effects of GLP-1 on glycaemic control, bodyweight, insulin resistance, and β-cell function in patients with type 2 diabetes.
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Patients
The patients were recruited from the Department of Endocrinology, Hvidovre Hospital, Denmark. Eligible patients had had type 2 diabetes diagnosed after the age of 40 years and normal concentrations of haemoglobin and creatinine and normal liver function. 20 patients were included in the study and assigned to either GLP-1 or saline. The first two consecutive eligible patients were assigned GLP-1 treatment, and the next two were assigned saline, and so on. Treatment allocation was concealed from
Results
Of the 20 patients enrolled, 10 were assigned to the GLP-1 group and 10 to the saline group (figure 1). One patient in the saline group was excluded at week 0 because no veins were accessible. Clinical characteristics of the assessable patients are shown in table 1.
For patients in the saline group, plasma concentrations of GLP-1 did not change (week 0, 10·8 pmol/L [SE 2·4]; week 1, 10·5 pmol/L [2·3]; week 6, 9·4 pmol/L [2·1]; p=0·8). By contrast, in the GLP-1 group, concentrations of GLP-1
Discussion
We found that GLP-1 significantly decreases concentrations of plasma glucose, haemoglobin A1c, fructosamine, and free fatty acids and improves insulin sensitivity and β-cell function in patients with type 2 diabetes. The study, however, has some methodological constraints. It was not randomised, nor was it carried out double blind, and such observational studies can overestimate intervention effects compared with randomised trials. However, the patients in our study were similar at entry, which
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