Comparator clinical trials of surrogate endpoints with albiglutide are in HARMONY

Introduction: Agonists of glucagon-like peptide-1 (GLP-1) receptors are used in the treatment of type 2 diabetes. Albiglutide is a new long acting GLP-1 receptor agonist being developed for once-weekly use. Areas covered: This evaluation is of 2 clinical trials in the HARMONY clinical trials series. HARMONY 3 compares albiglutide to sitagliptin and glimepiride in subjects with type 2 diabetes poorly controlled with metformin, and HARMONY 6 compares albiglutide to insulin lispro in subjects poorly controlled with slow/medium release preparations of insulin. Expert opinion: Both studies showed that albiglutide lowered HbA1c, and had advantages over its comparator drugs. However, questions remain about the safety of albiglutide. Albiglutide is not being used in subjects with a history of thyroid cancer, as it is not known whether this is a rare adverse effect with albiglutide. Also, the safety of albiglutide in subjects with type 2 diabetes and high cardiovascular risk is unknown.

Pharmacotherapies to manage diabesity:an update

Several pharmacotherapies have recently become available for addition to lifestyle measures to assist the management of coexistent type 2 diabetes and obesity. These are mostly administered as add-on to metformin or as alternative therapies if metformin is not appropriate. The sodium–glucose cotransporter 2 inhibitors (dapagliflozin, canagliflozin and empagliflozin) act by eliminating excess glucose in the urine. These agents provide a non-insulin-dependent mechanism to reduce hyperglycaemia and facilitate weight loss without causing frank hypoglycaemia. Their efficacy requires the individual to have adequate renal function. The glucagon-like peptide-1 (GLP-1) receptor agonists (exenatide, liraglutide, lixisenatide, dulaglutide and albiglutide [the last at the pre-launch stage at the time of writing]) are injected subcutaneously. Different members of the class offer different time courses for their onset and duration of action. Each potentiates insulin secretion and reduces glucagon secretion in a glucose-dependent manner to address prandial glycaemic excursions while avoiding interprandial hypoglycaemia. A satiety effect of these agents assists weight reduction, but delayed gastric emptying can cause initial nausea. The dipeptidyl peptidase-4 inhibitor class now comprises sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin. These agents offer similar glucose-lowering efficacy without weight gain or hypoglycaemia by boosting the half-life of endogenous incretins, particularly GLP-1. A fixed-ratio injected combination of insulin degludec with liraglutide (IDegLira) has recently been launched and further agents to address hyperglycaemia and assist weight loss are advancing in development.