Abstract
Type 2 diabetes mellitus (T2DM) continues to be a substantial medical problem due to its increasing global prevalence and because chronic hyperglycemic states are closely linked with obesity, liver disease and several cardiovascular diseases. Since the early discovery of insulin, numerous antihyperglycemic drug therapies to treat diabetes have been approved, and also discontinued, by the United States Food and Drug Administration (FDA). To provide an up-to-date account of the current trends of antidiabetic pharmaceuticals, this review offers a comprehensive analysis of the main classes of antihyperglycemic compounds and their mechanisms: insulin types, biguanides, sulfonylureas, meglitinides (glinides), alpha-glucosidase inhibitors (AGIs), thiazolidinediones (TZD), incretin-dependent therapies, sodium-glucose cotransporter type 2 (SGLT2) inhibitors and combinations thereof. The number of therapeutic alternatives to treat T2DM are increasing and now there are nearly 60 drugs approved by the FDA. Beyond this there are nearly 100 additional antidiabetic agents being evaluated in clinical trials. In addition to the standard treatments of insulin therapy and metformin, there are new drug combinations, e.g., containing metformin, SGLT2 inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors, that have gained substantial use during the last decade. Furthermore, there are several interesting alternatives, such as lobeglitazone, efpeglenatide and tirzepatide, in ongoing clinical trials. Modern drugs, such as glucagon-like peptide-1 (GLP-1) receptor agonists, DPP4 inhibitors and SGLT2 inhibitors have gained popularity on the pharmaceutical market, while less expensive over the counter alternatives are increasing in developing economies. The large heterogeneity of T2DM is also creating a push towards more personalized and accessible treatments. We describe several interesting alternatives in ongoing clinical trials, which may help to achieve this in the near future.
Highlights
This year marks the 100th anniversary of the pioneering experiments by Banting, and later on Best, Macleod and Collip, that led to the discovery of insulin to treat diabetes (Quianzon and Cheikh, 2012)
We have provided a comprehensive study of the clinical trials and Food and Drug Administration (FDA) approved drugs in relationship to their therapeutic targets
It is clear that the number of therapeutic alternatives to treat type 2 diabetes mellitus (T2DM) are increasing and there are nearly 60 drugs approved by the FDA
Summary
This year marks the 100th anniversary of the pioneering experiments by Banting, and later on Best, Macleod and Collip, that led to the discovery of insulin to treat diabetes (Quianzon and Cheikh, 2012). A broad range of drug therapies has been approved by the United States Food and Drug Administration (FDA) that address different biological systems and mechanisms implicated in the disease (Gourgari et al, 2017) In this rapidly developing area of pharmacology, hundreds of compounds with antihyperglycemic activity have been discovered in nature or synthesized in recent years, many of which are currently undergoing clinical trials (Artasensi et al, 2020). An updated comprehensive analysis is needed to examine the current state of diabetes drug discovery and search for new diabetology approaches This analysis aims to shed light on the current trends of FDAapproved antidiabetic pharmaceuticals and all the drugs to treat diabetes in clinical development from 2015 to 2020. We will discuss the mechanisms of action of the main classes of antihyperglycemic compounds and present new and promising, but not yet approved, therapeutic approaches for treating T2DM
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
