Published online Dec 15, 2018. doi: 10.4239/wjd.v9.i12.209
Peer-review started: August 29, 2018
First decision: October 5, 2018
Revised: November 20, 2018
Accepted: November 26, 2018
Article in press: November 26, 2018
Published online: December 15, 2018
Type 2 diabetes mellitus (DM) is a lifelong metabolic disease, characterized by hyperglycaemia which gradually leads to the development and progression of vascular complications. It is recognized as a global burden disease, with substantial consequences on human health (fatality) as well as on health-care system costs. This review focuses on the topic of historical discovery and understanding the complexity of the disease in the field of pathophysiology, as well as development of the pharmacotherapy beyond insulin. The complex interplay of insulin secretion and insulin resistance developed from previously known “ominous triumvirate” to “ominous octet” indicate the implication of multiple organs in glucose metabolism. The pharmacological approach has progressed from biguanides to a wide spectrum of medications that seem to provide a beneficial effect on the cardiovascular system. Despite this, we are still not achieving the target treatment goals. Thus, the future should bring novel antidiabetic drug classes capable of acting on several levels simultaneously. In conclusion, given the raising burden of type 2 DM, the best present strategy that could contribute the most to the reduction of morbidity and mortality should be focused on primary prevention.
Core tip: Type 2 diabetes mellitus (DM) is a global burden disease and one of the leading all-cause mortality causes due to cardiovascular (CV) complications. The rapid raise in the understanding of its pathogenesis resulted in treatment approach options beyond insulin that also provide beneficial CV effect. We discuss this scientific pathological and pharmacological development through a comprehensive historical approach. The wide spectrum of therapeutic agents currently used in type 2 DM treatment result in a CV mortality reduction which is not exclusively in correlation with glucose-lowering potency but is linked to its mechanism of action.