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

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 initiated dapagliflozin in 2015-2016 and 14,801 patients who initiated 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 initiated 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.

Predictors of cardio-kidney complications and treatment failure in patients with chronic kidney disease and type 2 diabetes treated with SGLT2 inhibitors

“…The discontinuation rates found in our study population were slightly higher than existing research on discontinuation of SGLT2i among T2D patients [ 14 , 25 ], which could be explained by the development of SGLT2i adverse events. These events were higher among patients with treatment failure compared to their counterparts during follow-up (Additional file 1 : Table S3), specifically diabetic ketoacidosis among commercially insured patients and volume depletion among the older Medicare patients, although the percentages of patients with these adverse event during follow-up was in line with the percentages at baseline in the overall population.…”

Poor adherence and persistence to sodium glucose co‐transporter 2 inhibitors in real‐world settings: Evidence from a systematic review and meta‐analysis

“…Two additional articles were retrieved via reference screening, resulting in 22 studies (involving 31 cohorts) being included in the review (Figure 1). 36‐57 The descriptive characteristics of the studies are presented in Table 1. The included studies, which comprised 123 854 individuals prescribed SGLT2 inhibitors, were published from 2015 to 2019 and were from eight different countries: Australia (n = 1), Taiwan (n = 1), Canada (n = 1), UK (n = 2), Hungary (n = 1), Pakistan (n = 1), Italy (n = 2), and United States (n = 13).…”

“…However, the definition of non‐persistence varied across studies. Three studies defined non‐persistence as a gap of ≥60 days, 34,36,41 one study used a gap of ≥180 days, 49 seven studies defined non‐persistence as a gap of ≥90 days 39,40,43,51‐53,55 and five used other definitions 44‐46,50,54 . Nine studies (10 cohorts) involving 80 894 individuals reported that 72.5% to 95.7% were persistent to SGLT2 inhibitors at six months.…”

Adherence and persistence rates of major antidiabetic medications: a review

“…SGLT2 inhibitors block glucose reabsorption in the renal proximal tubules of the kidneys [ 41 , 46 , 47 ]. Their distinct mechanism of action entails a distinct set of adverse events, such as orthostatic hypotension, ketoacidosis, and most notably, genitourinary tract infections [ 48 , 49 ]. The unique safety profile of SGLT2 inhibitors led to a distinct factor for persistence.…”

“…For example, higher estimated glomerular filtration rate (eGFR) was associated with significantly lower persistence rate (the beta coefficient [standard error] for discontinuation per one-unit increase in eGFR: 0.01 [± 0.00], p < 0.001) [ 49 ]. The increased likelihood of genitourinary tract infections due to the hyperfiltration of urinary glucose excretion was proposed as a reason for the association [ 49 ]. Similar conclusions were made by other studies [ 48 , 50 ].…”