Incretin-based therapy in combination with basal insulin: A promising tactic for the treatment of type 2 diabetes

• Published in: Diabetes & metabolism Vol. 39; no. 1; pp. 6 - 15
• Main Authors: Vora, J, Bain, S.C, Damci, T, Dzida, G, Hollander, P, Meneghini, L.F, Ross, S.A
• Format: Journal Article
• Language: English
• Published: Paris Elsevier Masson SAS 01.02.2013; Masson
• Subjects: Analogues du GLP-1; Association; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Body Weight - drug effects; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Diabète de type 2; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; DPP-IV inhibitors; Drug Therapy, Combination; Endocrine pancreas. Apud cells (diseases); Endocrinology & Metabolism; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; GLP-1 analogue; Glycated Hemoglobin A - drug effects; Glycated Hemoglobin A - metabolism; HbA1c; Humans; Hypoglycemic Agents - therapeutic use; Incretins - therapeutic use; Inhibiteurs des DPP-IV; Insulin; Insulin - therapeutic use; Insulinothérapie basale; Internal Medicine; Male; Medical sciences; Metformin - therapeutic use; Poids; Review; Revue générale; Treatment Outcome; Type 2 diabetes mellitus; Weight; Weight Loss; Analogues du GLP-1; Poids; Insulinothérapie basale; Type 2 diabetes mellitus; Review; Insulin; Weight; Diabète de type 2; Association; HbA 1c; Inhibiteurs des DPP-IV; GLP-1 analogue; DPP-IV inhibitors; Revue générale; HbA1c; Endocrinopathy; Type 2 diabetes; Incretin; Pancreatic hormone; Treatment; Analog; Metabolic diseases; Dipeptidyl-peptidase IV inhibitor
• ISSN: 1262-3636; 1878-1780
• DOI: 10.1016/j.diabet.2012.08.002

Abstract Incretin therapies such as dipeptidyl peptidase-4 inhibitors (DPP-4Is) and GLP-1 receptor agonists (GLP-1RAs) have become well-established treatments for type 2 diabetes. Both drug classes reduce blood glucose through physiological pathways mediated by the GLP-1 receptor, resulting in glucose-dependent enhancement of residual insulin secretion and inhibition of glucagon secretion. In addition, the GLP-1RAs reduce gastrointestinal motility and appear to have appetite-suppressing actions and, so, are often able to produce clinically useful weight loss. The glucose-dependency of their glucagon-inhibiting and insulin-enhancing effects, together with their weight-sparing properties, make the incretin therapies a logical proposition for use in combination with exogenous basal insulin therapy. This combination offers the prospect of an additive or synergistic glucose-lowering effect without a greatly elevated risk of hypoglycaemia compared with insulin monotherapy, and any insulin-associated weight gain might also be mitigated. Furthermore, the incretin therapies can be combined with metformin, which is usually continued when basal insulin is introduced in type 2 diabetes. Although the combination of incretin and insulin therapy is currently not addressed in internationally recognized treatment guidelines, several clinical studies have assessed its use. The data, summarized in this review, are encouraging and show that glycaemic control is improved and weight gain is limited or reversed (especially with the combined use of GLP-1RAs and basal insulin), and that the use of an incretin therapy can also greatly reduce insulin dose requirements. The addition of basal insulin to established incretin therapy is straightforward, but insulin dose adjustment (though not discontinuation) is usually necessary if the sequence is reversed.