Pharmacoepidemiol Drug Saf. 2026 Apr;35(4):e70352. doi: 10.1002/pds.70352.
ABSTRACT
PURPOSE: Both angiotensin-converting enzyme inhibitors (ACEis) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) provide cardiovascular and renal benefits in Type 2 Diabetes (T2D) patients, suggesting advantages from co-administration. However, evidence on ACEi usage patterns among SGLT2i users is limited. We aim to examine the utilization and discontinuation of ACEi in SGLT2i new users.
METHODS: Using 2012-2020 Medicare data, we conducted a retrospective study and included SGLT2i new users who filled ≥ 1 ACEi prescription(s) at the time of or after SGLT2i initiation. Patients were followed from the index date (first ACEi prescription filled after SGLT2i initiation) for 12 months or death, disenrollment, or end of the study (12/31/2020). ACEi discontinuation was defined as a treatment gap of ≥ 60 days. Cox proportional hazards models were constructed to identify factors associated with time to ACEi discontinuation.
RESULTS: Among 9717 SGLT2i initiators, 4798 (49.4%) utilized ACEi at the time of SGLT2i initiation, and 1221 of these patients (25.45%) discontinued their ACEi within 12 months of SGLT2i initiation. ACEi initiation at or after the time of SGLT2i initiation (adjusted hazard ratio [aHR] = 1.89), angiotensin receptor blockers (aHR = 1.46) use, acute myocardial infarction (aHR = 1.31), stroke or transient ischemic stroke (aHR = 1.26), and Black or Hispanic (aHR = 1.48 and 1.55) patients were independently associated with higher discontinuation risk. Older age (aHR = 0.78 for age 65-75) and metformin use (aHR = 0.74) were associated with reduced discontinuation risk.
CONCLUSIONS: Approximately one quarter of ACEi users discontinued their therapy within 1 year of SGLT2i initiation. We found that patient demographics, use of other medications, and clinical history were associated with ACEi discontinuation. These findings highlight the need for individualized strategies to support persistence with cardioprotective therapies in T2D care.
PMID:41862429 | DOI:10.1002/pds.70352