Dipeptidyl peptidase 4 inhibitors in the treatment of type 2 diabetes: what do we know today?

• Anna L. Terekhova

Abstract

Diabetes remains one of the most significant medical and social problems of our time. Main manifestation of the disease is chronic hyperglycaemia, ultimately leading to microvascular (retinopathy, nephropathy, neuropathy) damage and to macrovascular events like myocardial infarction, cerebrovascular insults, and complications related to peripheral vascular disease, including the diabetic foot syndrome. The risk for neoplastic diseases is also increased in people with diabetes. Although the development of complications is higher in patients with associated arterial hypertension and lipid disorders. Dipeptidyl peptidase 4 inhibitors (DPP4-I) became one of the most broadly used class of glucose-lowering drugs currently. The glucose-lowering efficacy and favorable safety profile, as well as the protective effect on β-cell function, allow to use this medicine at the earliest stages of the disease.

Compared to other hypoglycemic drugs, DPP4-I could act against the age-related muscle atrophy. Vildagliptin is a selective DPP4-I that can produce 1.5- to 3-fold increase in postprandial active plasma glucagon-like peptide‑1 (GLP‑1) levels versus placebo. Vildagliptin also improved β-cell function and stimulated β-cell mass increase. Numerous clinical studies have demonstrated improved glycated hemoglobin and reduced fasting plasma and postprandial plasma glucose in type 2 diabetic mellitus (T2DM) patients when used vildagliptin in monotherapy or in combination with some other antidiabetic drugs. Meta-analysis of a large pool of studies, including trials in high-risk patients with T2DM, such as those with congestive heart failure (HF) and/or moderate/severe renal impairment showed that vildagliptin was not associated with an increased risk of adjudicated MACEs (major adverse cardiac events) or a increased risk of HF development. The approval of high-quality generics of vildagliptin make it more affordable to use in clinical practice. The Gedeon Richter company introduced to the Russian market the drugs Agarta^® and Agarta Met^® (50+500, 50+850 and 50+1000 mg), which can be widely used by endocrinologists in real clinical practice.

Keywords:dipeptidyl peptidase 4 inhibitors; type 2 diabetes mellitus; treatment; vildagliptin

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