Combining GLP-1 receptor agonists with insulin: therapeutic rationales and clinical findings

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 -