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

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

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.871052

DOI=10.3389/fphar.2022.871052

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> To verify whether, in patients on metformin (MET) monotherapy for type 2 diabetes (T2D), the add-on of a <ext-link ext-link-type="uri" xlink:href="https://www.google.com/search?rlz=1C1GCEV_en&amp;q=dipeptidyl+peptidase+inhibitor&amp;spell=1&amp;sa=X&amp;ved=0ahUKEwiuq57NyvXhAhVOalAKHcmbDd0QkeECCCooAA" xmlns:xlink="http://www.w3.org/1999/xlink">dipeptidyl peptidase inhibitor</ext-link> (DPP4i) compared to a sulfonylurea (SU) can delay the time to the subsequent treatment intensification (TI).</p><p><bold>Methods:</bold> 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 &gt;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.</p><p><bold>Results:</bold> 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).</p><p><bold>Conclusion:</bold> The use of a DPP4i rather than a SU as add-on to MET monotherapy was not associated with a delay in treatment intensification.</p>