Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Dec 15, 2018; 9(12): 209-219
Published online Dec 15, 2018. doi: 10.4239/wjd.v9.i12.209
Treatment approach to type 2 diabetes: Past, present and future
Kristina Blaslov, Fran Stjepan Naranđa, Ivan Kruljac, Ivana Pavlić Renar
Kristina Blaslov, Ivan Kruljac, Department of Endocrinology, Diabetes and Metabolic Diseases Mladen Sekso, University Hospital Center Sestre Milosrdnice, Zagreb 10000, Croatia
Fran Stjepan Naranđa, Ivana Pavlić Renar, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
Author contributions: Blaslov K and Pavlić Renar I conceived of and designed the study; Kruljac I and Naranđa SF searched the literature; Blaslov K and Kruljac I drafted the article; all authors revised the article for important intellectual content; Pavlić Renar I gave final approval for the article.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author to: Kristina Blaslov, MD, PhD, Doctor, Department of Endocrinology, Diabetes and Metabolic Diseases Mladen Sekso, University Hospital Center Sestre Milosrdnice, Vinogradska cesta 29, Zagreb 10000, Croatia.
Telephone: +385-1-3787111 Fax: +385-1-3769067
Received: August 29, 2018
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.

Keywords: Type 2 diabetes mellitus, Physical activity, Hyperglycaemia, Insulin resistance, Hypoglycaemic agents

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.