Abstract

Type 2 diabetes mellitus is a growing global public health problem, the prevalence of which is projected to increase in the succeeding decades. It is potentially associated with many complications, affecting multiple organs and causing a huge burden to the society. Due to its multi-factorial pathophysiology, its treatment is varied and based upon a multitude of pharmacologic agents aiming to tackle the many aspects of the disease pathophysiology (increasing insulin availability [either through direct insulin administration or through agents that promote insulin secretion], improving sensitivity to insulin, delaying the delivery and absorption of carbohydrates from the gastrointestinal tract, or increasing urinary glucose excretion). DPP-4 (dipeptidyl peptidase-4) inhibitors (or “gliptins”) represent a class of oral anti-hyperglycemic agents that inhibit the enzyme DPP-4, thus augmenting the biological activity of the “incretin” hormones (glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) and restoring many of the pathophysiological problems of diabetes. They have already been used over more than a decade in the treatment of the disease. The current manuscript will review the mechanism of action, therapeutic utility, and the role of DPP-4 inhibitors for the treatment of type 2 diabetes mellitus.

Highlights

  • Diabetes mellitus (DM) is a complex, chronic illness requiring continuous medical care with multifactorial risk-reduction strategies in order to reduce complications

  • A recent meta-analysis combining the results of long-term clinical trials suggested that the effect of Dipeptidyl peptidase-4 (DPP-4) inhibitors on HbA1c levels in patients with T2DM may decline during the second year of treatment [70], direct head-to-head comparison of glycemic durability of DPP-4 inhibitors and sulfonylureas showed that DPP-4 inhibitors were associated with significantly smaller increases in the HbA1c level from 24 to 28 weeks to 104 weeks and from 52 weeks to 104 weeks

  • Association (ADA) 2019 Scientific Sessions, showed that there were no major differences in cardiovascular outcomes between the DPP-4 inhibitor linagliptin and the sulfonylurea glimepiride among patients with early type 2 diabetes at increased cardiovascular risk

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Summary

Introduction

Diabetes mellitus (DM) is a complex, chronic illness requiring continuous medical care with multifactorial risk-reduction strategies in order to reduce complications. Due to the current pharmacologic therapeutic approaches are based upon increasing insulin availability Apart from lifestyle modifications to reduce through healthysecretion), diet and through directitsinsulin administration or through agents thatobesity promote insulin improving encouragement of physical activity, current pharmacologic therapeutic approaches are based sensitivity to insulin, delaying the delivery and absorption of carbohydrate from the gastrointestinal upon increasing insulin availability Dipeptidyl-peptidase-4 (DPP-4) inhibitors (or ‘gliptins’) represent a class of oral and glucose-dependent insulinotropic polypeptide (GIP), affect glucose control through anti-hyperglycemic agents that block the inactivation of and the “incretin”.

The “Incretin”
The DPP-4 Enzyme
DPP-4 Inhibitors
Glycemic Efficacy
Cardiovascular Effects
Mortality
Adverse Effects
Use in Special Populations
Elderly Persons with T2D
Conclusions
Full Text
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