Acta Diabetologica

, Volume 56, Issue 6, pp 605–617 | Cite as

Ten years of experience with DPP-4 inhibitors for the treatment of type 2 diabetes mellitus

  • Giorgio SestiEmail author
  • Angelo Avogaro
  • Sara Belcastro
  • Benedetta Maria Bonora
  • Marina Croci
  • Giuseppe Daniele
  • Marco Dauriz
  • Francesco Dotta
  • Caterina Formichi
  • Simona Frontoni
  • Cecilia Invitti
  • Emanuela Orsi
  • Fabiana Picconi
  • Veronica Resi
  • Enzo Bonora
  • Francesco Purrello
Review Article


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.


DPP-4 inhibitors Diabetes Hypoglycemia Cardiovascular outcome trial 



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.

Compliance with ethical standards

Conflict of interest

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.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study, formal consent is not required.


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Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2019

Authors and Affiliations

  • Giorgio Sesti
    • 1
    Email author
  • Angelo Avogaro
    • 2
  • Sara Belcastro
    • 3
  • Benedetta Maria Bonora
    • 2
  • Marina Croci
    • 4
  • Giuseppe Daniele
    • 5
  • Marco Dauriz
    • 6
  • Francesco Dotta
    • 7
  • Caterina Formichi
    • 7
  • Simona Frontoni
    • 8
  • Cecilia Invitti
    • 4
  • Emanuela Orsi
    • 9
  • Fabiana Picconi
    • 8
  • Veronica Resi
    • 9
    • 10
  • Enzo Bonora
    • 6
  • Francesco Purrello
    • 11
  1. 1.Department of Clinical and Surgical ScienceUniversity of Magna Graecia of CatanzaroCatanzaroItaly
  2. 2.Department of MedicineUniversity of PadovaPadovaItaly
  3. 3.Department of Medical SciencesUniversity of TurinTurinItaly
  4. 4.Department of Medical Sciences and RehabilitationIRCCS Istituto Auxologico ItalianoMilanItaly
  5. 5.Department of Clinical and Experimental Medicine A.O.U. PisanaPisaItaly
  6. 6.Division of Endocrinology, Diabetes and Metabolism, Department of MedicineUniversity of Verona and Hospital Trust of VeronaVeronaItaly
  7. 7.Diabetes Unit, Department of Medicine, Surgery and NeuroscienceUniversity of SienaSienaItaly
  8. 8.Unit of Endocrinology, Diabetes and Metabolism, Department of Systems Medicine, S. Giovanni Calibita Fatebenefratelli HospitalUniversity of Rome Tor VergataRomeItaly
  9. 9.Diabetes UnitFondazione IRCCS’Cà Granda-Ospedale Maggiore PoliclinicoMilanItaly
  10. 10.Department of Clinical Sciences and Community HealthUniversity of MilanMilanItaly
  11. 11.Department of Clinical and Experimental MedicineUniversity of CataniaCataniaItaly

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