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Review
. 2022 Jan 11;58(1):109.
doi: 10.3390/medicina58010109.

Experimental and Emerging Free Fatty Acid Receptor Agonists for the Treatment of Type 2 Diabetes

Angelo Maria Patti  1 , Rosaria Vincenza Giglio  2 , Nikolaos Papanas  3 , Dragos Serban  4 , Anca Pantea Stoian  5 , Kalliopi Pafili  3 , Khalid Al Rasadi  6 , Kanya Rajagopalan  7 , Ali A Rizvi  7   8 , Marcello Ciaccio  2   9 , Manfredi Rizzo  1   5   8
Affiliations
Review

Experimental and Emerging Free Fatty Acid Receptor Agonists for the Treatment of Type 2 Diabetes

Angelo Maria Patti et al. Medicina (Kaunas). .

Abstract

The current management of Type 2 Diabetes Mellitus (T2DM) includes incretin-based treatments able to enhance insulin secretion and peripheral insulin sensitivity as well as improve body mass, inflammation, plasma lipids, blood pressure, and cardiovascular outcomes. Dietary Free Fatty Acids (FFA) regulate metabolic and anti-inflammatory processes through their action on incretins. Selective synthetic ligands for FFA1-4 receptors have been developed as potential treatments for T2DM. To comprehensively review the available evidence for the potential role of FFA receptor agonists in the treatment of T2DM, we performed an electronic database search assessing the association between FFAs, T2DM, inflammation, and incretins. Evidence indicates that FFA1-4 agonism increases insulin sensitivity, induces body mass loss, reduces inflammation, and has beneficial metabolic effects. There is a strong inter-relationship between FFAs and incretins. FFA receptor agonism represents a potential target for the treatment of T2DM and may provide an avenue for the management of cardiometabolic risk in susceptible individuals. Further research promises to shed more light on this emerging topic.

Keywords: GLP-1; Type 2 diabetes; cardiovascular risk; free fatty acids; incretins; metabolism.

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Conflict of interest statement

This article has been written independently and solely reflects the opinion of the authors. Nikolaos Papanas has been an advisory board member of TrigoCare International, Abbott, AstraZeneca, Elpen, MSD, Novartis, Novo Nordisk, Sanofi-Aventis, and Takeda; he has participated in sponsored studies by Eli Lilly, MSD, Novo Nordisk, Novartis, and Sanofi-Aventis; he has received honoraria as a speaker for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Elpen, Galenica, MSD, Mylan, Novartis, Novo Nordisk, Pfizer, Sanofi-Aventis, Takeda, and Vianex; and has attended conferences sponsored by TrigoCare International, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novartis, Novo Nordisk, Pfizer, and Sanofi-Aventis. Anca Pantea Stoian is currently Vice President of Romanian National Diabetes Committee and she has given lectures, received honoraria, and research support, and participated in conferences, advisory boards, and clinical trials sponsored by many companies, including AstraZeneca, Boehringer Ingelheim, Coca-Cola, Medtronic, Eli Lilly, Merck, Novo Nordisk, Novartis, Roche Diagnostics, and Sanofi. Manfredi Rizzo is former Director, Clinical Medical and Regulatory Department, Novo Nordisk Europe East and South and he has given lectures, received honoraria, and research support, and participated in conferences, advisory boards and clinical trials sponsored by many pharmaceutical companies including Amgen, AstraZeneca, Boehringer Ingelheim, Kowa, Eli Lilly, Meda, Mylan, Merck Sharp and Dohme, Novo Nordisk, Novartis, Roche Diagnostics, Sanofi, and Servier. None of the above mentioned companies had any role in this article, which has been written independently, without any financial or professional help, and reflects only the opinion of the authors, without any role of the industry.

Figures

Figure 1
Figure 1
Potential actions of free fatty acids 1 receptor (FFA1R) and free fatty acids 4 receptor (FFA4R) agonists.
See this image and copyright information in PMC

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