Time to Treatment Intensification in Patients Receiving DPP4 Inhibitors Versus Sulfonylureas as the First Add-On to Metformin Monotherapy: A Retrospective Cohort Study

Giuseppe Roberto; Anna Girardi; Francesco Barone-Adesi; Alessandro Pecere; Valentina Ientile; Claudia Bartolini; Roberto Da Cas; Stefania Spila-Alegiani; Carmen Ferrajolo; Paolo Francesconi; Gianluca Trifirò; Elisabetta Poluzzi; Fabio Baccetti; Rosa Gini

doi:10.3389/fphar.2022.871052

Time to Treatment Intensification in Patients Receiving DPP4 Inhibitors Versus Sulfonylureas as the First Add-On to Metformin Monotherapy: A Retrospective Cohort Study

Front Pharmacol. 2022 May 30:13:871052. doi: 10.3389/fphar.2022.871052. eCollection 2022.

Affiliations

¹ Osservatorio di Epidemiologia, Agenzia Regionale di Sanità Della Toscana, Firenze, Italy.
² Dipartimento di Medicina Traslazionale, Università Del Piemonte Orientale, Novara, Italy.
³ Dipartimento di Scienze Biomediche, Odontoiatriche e Delle Immagini Morfologiche e Funzionali, Università Degli Studi di Messina, Messina, Italy.
⁴ Centro Nazionale per la Ricerca e la Valutazione Preclinica e Clinica Dei Farmaci, Istituto Superiore di Sanità, Roma, Italy.
⁵ Dipartimento di Medicina Sperimentale, Università Degli Studi Della Campania "L. Vanvitelli" e Centro Regionale di Farmacovigilanza, Regione Campania, Napoli, Italy.
⁶ Unità di Farmacologia, Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy.
⁷ Unità Operativa di Diabetologia Massa-Carrara, USL Toscana Nordovest, Massa, Italy.

Abstract

Background: To verify whether, in patients on metformin (MET) monotherapy for type 2 diabetes (T2D), the add-on of a dipeptidyl peptidase inhibitor (DPP4i) compared to a sulfonylurea (SU) can delay the time to the subsequent treatment intensification (TI). Methods: Population-based administrative data banks from four Italian geographic areas were used. Patients aged ≥18 years on MET monotherapy receiving first DPP4i or SU dispensing between 2008 and 2015 (cohort entry) were followed up to the occurrence of TI (insulin dispensing or add-on of a third non-insulin hypoglicemic >180 days after cohort entry), treatment discontinuation, switch, cancer, death, TI occurrence within, end of data availability, end of study period (31 December 2016), whichever came first. Patients on MET + DPP4i were matched 1:1 with those on MET + SU by sex, age, year of cohort entry, and data bank. Hazard Ratio (HR) and 95% confidence intervals (95%CI) were estimated using multivariable Cox regression model including matching variables and potential confounders measured at baseline. Different sensitivity analyses were performed: i) matching at 180 days after cohort entry, ii) intent to treat (ITT) analysis, iii) matching by duration of MET monotherapy, iv) matching by propensity score. Results: The matched study cohort included 10,600 patients. Overall, 763 TI were observed (4.5/100 person-years; mean follow-up = 1.6 years). The primary analysis showed no difference in time to TI between the two groups (HR = 1.02; 95% CI = 0.88-1.19). Sensitivity analyses confirmed this result, except from the ITT analysis (HR = 1.27; 1.13-1.43). Conclusion: The use of a DPP4i rather than a SU as add-on to MET monotherapy was not associated with a delay in treatment intensification.

Keywords: DPP4i; durability; metformin; observational study; secondary failure; sulfonylurea; treatment intensification; type 2 diabetes.