Clinical Medicine Reviews in Vascular Health

Among the new therapeutic options for type 2 diabetes care, the incretin-based treatments are considered particularly promising. Two classes of drugs have been developed, GLP-1 receptor agonists and DPP-IV inhibitors, that respectively mimic or prolong the action of the human GLP-1, key-hormone in the glucose homeostasis maintenance.

Liraglutide is a GLP-1 analogue recently approved by the European Medicine Agency (EMEA). Efficacy and safety of liraglutide have been tested—in monotherapy and in combination with one or two other antidiabetic treatments—within a comprehensive program of six phase 3 randomized trials (LEAD 1–6), plus three extension phases and several meta-analyses. In the different LEAD studies, the maxi- mum dose of 1.8 mg/day of liraglutide produced after 26 weeks a decrease in HbA1c levels of 1.0%–1.5%, a reduction in fasting blood glucose by about 30 mg/dl, a decrease in body weight of 1–3 Kg, low rates of hypoglycemia, and additional benefits on cardiovascular risk factors. Transient nausea was the most common side effects. Patients treated with liraglutide 1.8 mg had a likelihood from 2 to 11 times greater to achieve one of the two clinically relevant composite endpoints examined (HbA1c < 7%/SBP < 130 mmHg/no weight gain or HbA1c < 7%/no weight gain/no hypoglycemia) as compared with any other placebo/active drugs. Incretin-based therapy has been currently approved for use as add-on therapy in T2DM patients not adequately controlled on maximum doses of metformin, sulfonylureas, TZDs, or their combination. However, if data on long-term efficacy and safety of these drugs will be confirmed, GLP-1 receptor agonists and especially liraglutide could represent an early strategy to delay disease progression and reduce the burden of diabetes and its complications.