Relationship Between Improvement in Insulin Secretion and Decrease in HbA1c in GLP-1 RA Therapy in T2DM Patients
Status:
Recruiting
Trial end date:
2023-07-15
Target enrollment:
Participant gender:
Summary
GLP-1 receptor agonists (GLP-1 RA) is group of antidiabetic agents very effective in lowering
the plasma glucose concentration in T2DM patients . Currently there are several agents
approved for the treatment of T2DM which are classified into two groups: (1) short acting
GLP-1 RA and include exenatide BID and lexisenatide, and (2) long acting agents which are
given once daily or weekly injection and include liraglutide, semaglutide, dulaglutide and
budyreon . Clinical studies have demonstrated that long acting GLP-1 RA (e.g. liraglutide,
bydureon and dulaglutide) produce ~1.5% reduction in the HbA1c , which was significantly
greater than that caused by other classes of antidiabetic agents (e.g. DPP4 inhibitors, and
SGLT2 inhibitors). Members of this class of drugs exert multiple metabolic actions in T2DM.
They potentiate insulin-stimulated insulin secretion from the beta cell , inhibit glucagon
secretion from the alpha cells and inhibit appetite and promote weight loss. Together, these
metabolic actions of GLP-1 RA contribute to the improvement in glucose metabolism and
decrease in HbA1c.
Although GLP-1 RA produce a robust mean decrease in HbA1c (~1.5%), the magnitude of decrease
in HbA1c in the individual patient vary considerably. Clinical studies showed that
approximately one third of T2DM patients receiving GLP-1 RA experience very modest to no
decrease in the HbA1c while another third of patients experience a robust decrease in the
HbA1c. the reason for this large variability in the individual response to GLP-1 RA is
unknown. Studies which attempted to identify possible clinical predictors that distinguish
between "good responders" and "poor responders" have failed to identify clinical parameter
that can predict the magnitude of decrease in HbA1c by GLP-1 RA in T2DM patients.
Because of the central role of beta cell function in the regulation of plasma glucose
concentration, the study investigators hypothesis that varying degree of beta cell response
to GLP-1 RA action is the principal factor responsible for the large variability in the
decrease in HbA1c by GLP-1 RA. The aim of the present study is to test this hypothesis.