Abstract
Achieving and maintaining recommended glycemic targets without causing adverse e ffects, including hypoglycemia, is challenging, especially in older patients with type 2 diabetes mellitus (T2DM). The introduction of dipeptidyl peptidase-4 (DPP-4) inhibitors, more than 10 years ago, has provided an alternative to conventional medications for the intensification of glucose-lowering treatment after failure of metformin monotherapy, and therefore, marked an important advance in the management of T2DM. By prolonging the activity of incretin hormones, DPP-4 inhibitors induce insulin release and decrease glucagon secretion in a glucose-dependent manner. This results in a more physiologic glycemic control as compared to that ensured by insulin secretagogues (sulfonylureas and glinides). Overall, DPP-4 inhibitors have a favorable safety profile and can be used without dose adjustments in older adults and in patients with mild renal impairment; they have a neutral effect on body weight and do not cause hypoglycemia by themselves. Safety issues, reported mainly in post-marketing surveillance programs and including cardiovascular outcomes and the risk of acute pancreatitis, are being extensively investigated. The aim of this review is to discuss the impact of DPP-4 inhibitors on the treatment of T2DM, after 10 years of experience, with an emphasis on diabetes care in Italy. We will first describe T2DM treatment in Italy and then provide an overview of the main findings from randomized controlled trials, real-world studies and post-marketing surveillance programs with DPP-4 inhibitors.
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We thank Lorenza Lanini, an independent medical writer, and Melanie Gatt (PhD), who provided editorial assistance, on behalf of Springer Healthcare Communications. This support was funded by Novartis.
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Giorgio Sesti has received speaker/consulting honoraria from Novo Nordisk, Eli Lilly, AstraZeneca, Boehringer Ingelheim, Merck, Novartis, Sanofi, Amgem, GlaxoSmithKline, Mylan, Abbott, and Servier. Angelo Avogaro has received research grants, lecture or advisory board fees from Merck Sharp & Dome, AstraZeneca, Novartis, Bayer, Boeringher-Ingelheim, Sanofi, Mediolanum, Janssen, NovoNordisk, Eli Lilly, Servier, Vifor Pharma, Jannsen, and Takeda. Sara Belcastro is a consultant for Novo nordisk, Mundipharma, Novartis, and Merck & co. Simona Frontoni has received honoraria for participating in advisory boards or speaking engagement from all companies producing medicine for diabetes care over the last 10 years. Her institution received research grant from Novo Nordisk, MSD, Ibsa. Cecilia Invitti has received a speaker honorarium from Guidotti. Benedetta Maria Bonora, Marina Croci, Giuseppe Daniele, Marco Dauriz, Francesco Dotta, Caterina Formichi, Emanuela Orsi, Fabiana Picconi and Veronica Resi declare that they have no conflict of interest. Enzo Bonora has received honoraria for participating in advisory boards or speaking engagement from all companies producing medicine for diabetes care over the last 10 years. His institution received research grant from Novo Nordisk, Takeda, AstraZeneca. Francesco Purrello has received honoraria for participating in advisory boards or speaking engagement from Eli Lilly, Novo Nordisk, Sanofi, MSD, AstraZeneca, Boheringer, GSK, Novartis, Menarini. His institution received research grant from Eli Lilly, Novo Nordisk, AstraZeneca.
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Sesti, G., Avogaro, A., Belcastro, S. et al. Ten years of experience with DPP-4 inhibitors for the treatment of type 2 diabetes mellitus. Acta Diabetol 56, 605–617 (2019). https://doi.org/10.1007/s00592-018-1271-3
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DOI: https://doi.org/10.1007/s00592-018-1271-3