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Predictors of early discontinuation of dapagliflozin versus other glucose-lowering medications: a retrospective multicenter real-world study

  • G. P. FadiniEmail author
  • P. Li Volsi
  • E. Devangelio
  • M. Poli
  • G. Cazzetta
  • G. Felace
  • A. Avogaro
  • for the DARWIN-T2D Network
Original Article
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Abstract

Background and aims

In routine clinical practice, early discontinuation of newly initiated glucose-lowering medications (GLM) is relatively common. We herein evaluated if the clinical characteristics associated with early discontinuation of dapagliflozin were different from those associated with early discontinuation of other GLM.

Methods

The DARWIN-T2D was a multicenter retrospective study conducted at diabetes specialist outpatient clinics in Italy. We included 2484 patients who were initiated on dapagliflozin in 2015–2016 and 14,801 patients who were initiated on other GLM (DPP-4 inhibitors, GLP-1 receptor agonists, or gliclazide) in the same period. After excluding patients who had not (yet) returned to follow-up, we compared the characteristics of patients who persisted on drug versus those who were no longer on drug at the first available follow-up after at least 3 months.

Results

As compared to those who persisted on drug, patients who discontinued dapagliflozin (51.7%) were more often female, had higher baseline fasting plasma glucose (FPG), HbA1c, and eGFR, and less common use of metformin. Upon multiple regression, higher HbA1c, higher eGFR, and lower metformin use remained independently associated with early discontinuation. Among patients who had been initiated on other GLM, 41.7% discontinued. Variables independently associated with discontinuation were older age, longer diabetes duration, higher HbA1c, eGFR, and albumin excretion, more common use of insulin and less metformin.

Conclusion

In routine clinical practice, all variables associated with dapagliflozin discontinuation were also associated with discontinuation of other GLM. Thus, despite a distinctive mechanism of action and a peculiar tolerability profile, no specific predictor of dapagliflozin discontinuation was detected.

Keywords

Adherence Pharmacotherapy Real-world Observational Type 2 diabetes 

Notes

Acknowledgements

We wish to thank Alessia Russo, Italian Diabetes Society, for the invaluable technical support. Composition of the DARWIN-T2D database: Agostino Consoli and Gloria Formoso (Dipartimento di Medicina e Scienze dell’Invecchiamento - Università Degli studi G. D’Annunzio di Chieti-Pescara); Giovanni Grossi (Ospedale San Francesco di Paola - Azienda Sanitaria Provinciale di Cosenza); Achiropita Pucci (Azienda Sanitaria Provinciale di Cosenza); Giorgio Sesti and Francesco Andreozzi (Azienda Ospedaliero Universitaria di Catanzaro); Giuseppe Capobianco (Azienda Sanitaria Locale Napoli 2 Nord); Adriano Gatti (Ospedale San Gennaro dei Poveri - Azienda Sanitaria Locale Napoli 1 Centro); Riccardo Bonadonna, Ivana Zavaroni and Alessandra Dei Cas (Azienda Ospedaliero Universitaria di Parma); Giuseppe Felace (Ospedale di Spilimbergo - Azienda per l’Assistenza Sanitaria n.5 Friuli Occidentale); Patrizia Li Volsi (Ospedale di Pordenone - Azienda per l’Assistenza Sanitaria n.5 Friuli Occidentale); Raffaella Buzzetti and Gaetano Leto (Ospedale Santa Maria Goretti - Azienda Sanitaria Locale di Latina); Gian Pio Sorice (Fondazione Policlinico Universitario A. Gemelli, Roma); Paola D’Angelo (Ospedale Sandro Pertini - Azienda Sanitaria Locale Roma 2); Susanna Morano (Azienda Ospedaliera Universitaria Policlinico Umberto I, Roma); Antonio Carlo Bossi (Ospedale di Treviglio - Azienda Socio Sanitaria Territoriale Bergamo Ovest); Edoardo Duratorre (Ospedale Luini Confalonieri di Luino - Azienda Socio Sanitaria Territoriale Sette Laghi); Ivano Franzetti (Ospedale Sant’Antonio Abate di Gallarate - Azienda Socio Sanitaria Territoriale Valle Olona); Paola Silvia Morpurgo (Ospedale Fatebenefratelli - Azienda Socio Sanitaria Territoriale Fatebenefratelli Sacco); Emanuela Orsi (Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico di Milano); Fabrizio Querci (Ospedale Pesenti Fenaroli di Alzano Lombardo - Azienda Socio Sanitaria Territoriale Bergamo Est); Massimo Boemi† and Federica D’Angelo (Presidio Ospedaliero di Ricerca INRCA-IRCCS di Ancona); Massimiliano Petrelli (Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona); Gianluca Aimaretti and Ioannis Karamouzis (Azienda Ospedaliero Universitaria Maggiore della Carità di Novara); Franco Cavalot (Azienda Ospedaliero Universitaria San Luigi Gonzaga, Orbassano); Giuseppe Saglietti† (Ospedale Madonna del Popolo di Omegna - Azienda Sanitaria Locale Verbano Cusio Ossola); Giuliana Cazzetta (Casa della Salute, Ugento - Distretto Socio Sanitario Gagliano del Capo - Azienda Sanitaria Locale di Lecce); Silvestre Cervone (Presidio ospedaliero San Marco in Lamis - Distretto Socio Sanitario San Marco in Lamis - Azienda Sanitaria Locale di Foggia); Eleonora Devangelio (Distretto Socio Sanitario di Massafra - Azienda Sanitaria Locale di Taranto); Olga Lamacchia (Azienda Ospedaliero Universitaria Ospedali Riuniti di Foggia); Salvatore Arena (Ospedale Umberto I - Azienda Sanitaria Provinciale di Siracusa); Antonino Di Benedetto (Azienda Ospedaliera Universitaria Policlinico G. Martino di Messina); Lucia Frittitta (Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi di Catania); Carla Giordano (Azienda Universitaria Policlinico Paolo Giaccone di Palermo); Salvatore Piro (Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi di Catania); Manfredi Rizzo, Roberta Chianetta and Carlo Mannina (Azienda Universitaria Policlinico Paolo Giaccone di Palermo); Roberto Anichini (Ospedale San Jacopo di Pistoia - Azienda USL Toscana Centro); Giuseppe Penno (Azienda Ospedaliero Universitaria Pisana); Anna Solini (Azienda Ospedaliera Universitaria Pisana); Bruno Fattor (Comprensorio Sanitario di Bolzano - Azienda Sanitaria della Provincia Autonoma di Bolzano); Enzo Bonora and Massimo Cigolini (Azienda Ospedaliero Universitaria Integrata di Verona); Annunziata Lapolla and Nino Cristiano Chilelli (Complesso Socio Sanitario Ai Colli - Azienda ULSS n.6 Euganea); Maurizio Poli (Ospedale Girolamo Fracastoro di San Bonifacio - Azienda ULSS n.9 Scaligera); Natalino Simioni and Vera Frison (Ospedale di Cittadella - Azienda ULSS n.6 Euganea); Carmela Vinci (Azienda ULSS n.4 Veneto Orientale).

Author contributions

Study design: GPF, AA. Data collection and analysis: GPF, PLV, ED, MP, GX, GF. Manuscript writing: GPF, AA. Manuscript revision: GPF, PLV, ED, MP, GC, GF AA. All authors approved the final version of the manuscript.

Funding

The study was partly supported by the Italian Diabetes Society, through a grant from AstraZeneca. The external sponsor had no role in the study design, data analysis and interpretation, and the decision to publish.

Compliance with ethical standards

Conflict of interest

GPF received grant support, lecture or advisory board fees from AstraZeneca, Boehringer-Ingelheim, Eli Lilly, NovoNordisk, Sanofi, Genzyme, Abbott, Mundipharma, Novartis, and Merck Sharp & Dohme. ED received grant support, lecture or advisory board fees from AstraZeneca, Eli Lilly, Lifescan, and NovoNordisk, Sanofi. GC received, lecture or advisory board fees from AstraZeneca, Lilly/Boehringer, Menarini, and Servier. AA received research grants, lecture or advisory board fees from Merck Sharp & Dome, AstraZeneca, Novartis, Boeringer-Ingelheim, Sanofi, Mediolanum, Janssen, and NovoNordisk. PLV, MP, and GF have nothing to disclose.

Ethical approval

The study has been conducted in compliance with ethical standards for research involving human participants. The study was approved by local ethical committees at each participating center.

Informed consent

The study was conducted on retrospectively collected anonymous patient records. Therefore, based on national regulations on retrospective studies, informed consent was not required.

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Copyright information

© Italian Society of Endocrinology (SIE) 2019

Authors and Affiliations

  1. 1.Department of MedicineUniversity of PadovaPaduaItaly
  2. 2.Ospedale di Pordenone - Azienda per l’Assistenza Sanitaria n.5, Friuli OccidentalePordenoneItaly
  3. 3.Presidio Territoriale di Assistenza-Distretto Socio Sanitario di Massafra - Azienda Sanitaria Locale di TarantoMassafraItaly
  4. 4.Ospedale Girolamo Fracastoro di San Bonifacio - Azienda ULSS n.9 ScaligeraSan BonifacioItaly
  5. 5.Distretto Socio Sanitario Gagliano del Capo, sede Tricase - Azienda Sanitaria Locale di LecceTricaseItaly
  6. 6.Ospedale di Spilimbergo - Azienda per l’Assistenza Sanitaria n.5, Friuli OccidentalePordenoneItaly

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