What is on the horizon for type 2 diabetes pharmacotherapy? – An overview of the antidiabetic drug development pipeline

ABSTRACT

Introduction

The number of people suffering from type 2 diabetes (T2D) and its complications is on the rise; and, thus continues to expand the market for pharmacologic agents targeting the disease. At present, only the glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose co-transporter 2 inhibitors (SGLT-2i) have demonstrated macrovascular benefits and reduction in mortality in T2D.

Areas covered

This review provides an overview of the more than 20 drug classes in clinical development for T2D, with an outline of their mode of action, efficacy, safety, and current status.

Expert opinion

New GLP-1 RA and SGLT-2i are dominating the clinical pipeline. A range of glucoregulatory hormone-based drugs are also under development (e.g. GLP-1/glucose-dependent insulinotropic polypeptide/glucagon receptor co-agonists) for the treatment of T2D and associated conditions such as obesity and nonalcoholic fatty liver disease. Glucokinase activators and imeglimin are in phase III of development. Other drugs in phase I–II (e.g. fructose-1,6-bisphosphatase inhibitors, activators of adenosine monophosphate-activated protein kinase and Lyn kinase; and agonists of the receptor for growth differentiation factor 15, fibroblast growth factor-21, and G protein-coupled receptor-119) show promising diverse mechanisms of action, but have yet to show net clinical benefits.

KEYWORDS:

• Antidiabetic
• type 2 diabetes (T2D)
• diabetes treatment
• pipeline
• development

Article highlights

• The increasing knowledge about T2D’ multifaceted pathophysiology and the close link to obesity and NAFLD is influencing the development of new antidiabetic drugs.

• Development of GLP-1 receptor agonist and SGLT2 inhibitors is dominating the developmental pipeline.

• Unimolecular drugs with dual or triple receptor engagement (e.g. GLP-1, GIP, and glucagon receptor agonists) are advancing in clinical development.

• Glucokinase activators and glimins may be close to market approval in some regions of the world.

• Pharmaceutical companies tend to drift their development plans to areas with less strictly regulated requirements than T2D, e.g. obesity and NAFLD.

This box summarizes key points contained in the article.

Declaration of interest

FK Knop has served on scientific advisory panels and/or been part of speaker’s bureaus for, served as a consultant to and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly and Company, Gubra, Lupin, MedImmune, Merck & Co, Mundipharma, Norgine, Novo Nordisk, Sanofi and Zealand Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This manuscript has not been funded.