TY - JOUR
T1 - Combining GLP-1 receptor agonists with insulin
T2 - therapeutic rationales and clinical findings
AU - Holst, Jens Juul
AU - Vilsbøll, T
N1 - © 2012 Blackwell Publishing Ltd.
PY - 2013/1
Y1 - 2013/1
N2 - Due to the increasing prevalence of type 2 diabetes mellitus (T2DM), the emergent trend towards diagnosis in younger patients and the progressive nature of this disease, many more patients than before now require insulin to maintain glycaemic control. However, there is a degree of inertia among physicians and patients regarding the initiation and intensification of insulin therapy, in part due to concerns about the associated weight gain and increased risk of hypoglycaemia. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase insulin release and suppress glucagon secretion in a glucose-dependent manner, thus conferring glycaemic control with a low incidence of hypoglycaemia. GLP-1RAs also promote weight loss, and have beneficial effects on markers of β cell function, lipid levels, blood pressure and cardiovascular risk markers. However, the durability of their effectiveness is unknown and, compared with insulin, the antihyperglycaemic efficacy of GLP-1RAs is limited. The combination of a GLP-1RA and insulin might thus be highly effective for optimal glucose control, ameliorating the adverse effects typically associated with insulin. Data from clinical studies support the therapeutic potential of GLP-1RA-insulin combination therapy, typically showing beneficial effects on glycaemic control and body weight, with a low incidence of hypoglycaemia and, in established insulin therapy, facilitating reductions in insulin dose. In this review, the physiological and pharmacological rationale for using GLP-1RA and insulin therapies in combination is discussed, and data from clinical studies that have assessed the efficacy and safety of this treatment strategy are outlined.
AB - Due to the increasing prevalence of type 2 diabetes mellitus (T2DM), the emergent trend towards diagnosis in younger patients and the progressive nature of this disease, many more patients than before now require insulin to maintain glycaemic control. However, there is a degree of inertia among physicians and patients regarding the initiation and intensification of insulin therapy, in part due to concerns about the associated weight gain and increased risk of hypoglycaemia. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase insulin release and suppress glucagon secretion in a glucose-dependent manner, thus conferring glycaemic control with a low incidence of hypoglycaemia. GLP-1RAs also promote weight loss, and have beneficial effects on markers of β cell function, lipid levels, blood pressure and cardiovascular risk markers. However, the durability of their effectiveness is unknown and, compared with insulin, the antihyperglycaemic efficacy of GLP-1RAs is limited. The combination of a GLP-1RA and insulin might thus be highly effective for optimal glucose control, ameliorating the adverse effects typically associated with insulin. Data from clinical studies support the therapeutic potential of GLP-1RA-insulin combination therapy, typically showing beneficial effects on glycaemic control and body weight, with a low incidence of hypoglycaemia and, in established insulin therapy, facilitating reductions in insulin dose. In this review, the physiological and pharmacological rationale for using GLP-1RA and insulin therapies in combination is discussed, and data from clinical studies that have assessed the efficacy and safety of this treatment strategy are outlined.
KW - Blood Glucose
KW - Diabetes Mellitus, Type 2
KW - Drug Administration Schedule
KW - Drug Therapy, Combination
KW - Female
KW - Glucagon-Like Peptide 1
KW - Hemoglobin A, Glycosylated
KW - Humans
KW - Hypoglycemic Agents
KW - Insulin
KW - Male
KW - Peptides
KW - Treatment Outcome
KW - Venoms
KW - Weight Gain
U2 - 10.1111/j.1463-1326.2012.01628.x
DO - 10.1111/j.1463-1326.2012.01628.x
M3 - Journal article
C2 - 22646532
SN - 1462-8902
VL - 15
SP - 3
EP - 14
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - 1
ER -
