- Title
- Clinical effectiveness of second-line antihyperglycemic drugs on major adverse cardiovascular events: An emulation of a target trial
- Creator
- Siriyotha, Sukanya; Lukkunaprasit, Thitiya; Angkananard, Teeranan; Looareesuwan, Panu; McKay, Gareth J.; Attia, John; Thakkinstian, Ammarin
- Relation
- Frontiers in Endocrinology Vol. 14, no. 1094221
- Publisher Link
- http://dx.doi.org/10.3389/fendo.2023.1094221
- Publisher
- Frontiers Research Foundation
- Resource Type
- journal article
- Date
- 2023
- Description
- Introduction: The cardiovascular benefits of multiple antihyperglycemic drugs as add-on therapies to metformin in the real-practice are unclear. This study aimed to directly compare major adverse cardiovascular events (CVE) associated with these multiple drugs. Methods: An emulation of a target trial was conducted using a retrospective-cohort data of type 2 diabetes mellitus (T2DM) prescribed with second-line drugs on top of metformin, including sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i), thiazolidinediones (TZD) and sulfonylureas (SUs). We applied inverse probability weighting and regression adjustment using intention-to-treat (ITT), per-protocol analysis (PPA) and modified ITT. Average treatment effects (ATE) were estimated using SUs as the reference. Results and Discussion: Among 25,498 patients with T2DM, 17,586 (69.0%), 3,261 (12.8%), 4,399 (17.3%), and 252 (1.0%) received SUs, TZD, DPP4i, and SGLT2i. Median follow-up time was 3.56 (1.36-7.00) years. CVE was identified in 963 patients. The ITT and modified ITT approaches showed similar results; the ATE (i.e., the difference of CVE risks) for SGLT2i, TZD, and DPP4i compared to SUs were -0.020(-0.040, -0.0002), -0.010(-0.017, -0.003), and -0.004(-0.010, 0.002), respectively, indicating 2% and 1% significant absolute risk reduction in CVE in SGLT2i and TZD compared to SUs. These corresponding effects were also significant in the PPA with ATEs of -0.045(-0.060, -0.031), -0.015(-0.026, -0.004), and -0.012(-0.020, -0.004). In addition, SGLT2i had 3.3% significant absolute risk reduction in CVE relative to DPP4i. Our study demonstrated benefits of SGLT2i and TZD in reducing CVE in T2DM patients compared to SUs when added to metformin.
- Subject
- diabetes; cardiovascular events; antihyperglycemic drugs; second-line; metformin
- Identifier
- http://hdl.handle.net/1959.13/1485474
- Identifier
- uon:51602
- Identifier
- ISSN:1664-2392
- Language
- eng
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