Abstract
Background: The cardiovascular benefits of second-line antidiabetic drugs add-on to metformin are unclear. This study aimed to evaluate major adverse cardiac events associated with second-line regimens following metformin treatment with sulfonylureas (SUs).
Methods: An emulation of a target trial was conducted on a 10-year retrospective cohort of patients with type 2 diabetes mellitus (T2DM) prescribed second-line drugs, including sodium-glucose cotransporter-2 inhibitor (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i), thiazolidinedione (TZD) and SUs. We applied treatment effect models with inverse probability weighting and regression adjustment using three approaches: intention-to-treat (ITT), per-protocol analysis (PPA) and modified ITT. An average treatment effect (ATE) and difference between potential outcome means (POM) were estimated using SUs as the reference.
Results: Totally 25,498 patients, 69.0%, 12.8%, 17.3%, and 1.0% received SUs, TZD, DPP4i, and SGLT2i as second line therapy. The CVD incidence (95% CI) in patients using SGLT2i, TZD, SUs, and DPP4i was 2.4% (0.9%, 5.1%), 2.9% (2.3%, 3.5%), 3.9% (3.6%, 4.2%), and 4.0% (3.5%, 4.6%), respectively. The differences in ATEs between POMs for SGLT2i, TZD, vs SUs, and DPP4i vs SUs were significant for both ITT, and PPA approaches, respectively.
Conclusion: Comparing to standard SU treatment secondary to metformin, our study illustrated significant added benefit of SGLT2i and TZD in reducing CVD incidence in patients with T2DM.
Methods: An emulation of a target trial was conducted on a 10-year retrospective cohort of patients with type 2 diabetes mellitus (T2DM) prescribed second-line drugs, including sodium-glucose cotransporter-2 inhibitor (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i), thiazolidinedione (TZD) and SUs. We applied treatment effect models with inverse probability weighting and regression adjustment using three approaches: intention-to-treat (ITT), per-protocol analysis (PPA) and modified ITT. An average treatment effect (ATE) and difference between potential outcome means (POM) were estimated using SUs as the reference.
Results: Totally 25,498 patients, 69.0%, 12.8%, 17.3%, and 1.0% received SUs, TZD, DPP4i, and SGLT2i as second line therapy. The CVD incidence (95% CI) in patients using SGLT2i, TZD, SUs, and DPP4i was 2.4% (0.9%, 5.1%), 2.9% (2.3%, 3.5%), 3.9% (3.6%, 4.2%), and 4.0% (3.5%, 4.6%), respectively. The differences in ATEs between POMs for SGLT2i, TZD, vs SUs, and DPP4i vs SUs were significant for both ITT, and PPA approaches, respectively.
Conclusion: Comparing to standard SU treatment secondary to metformin, our study illustrated significant added benefit of SGLT2i and TZD in reducing CVD incidence in patients with T2DM.
| Original language | English |
|---|---|
| Article number | 1874 |
| Number of pages | 1 |
| Journal | Journal of the American College of Cardiology |
| Volume | 81 |
| Issue number | 8, Supplement |
| DOIs | |
| Publication status | Published - 07 Mar 2023 |
| Externally published | Yes |
| Event | ACC.23 - New Orleans, United States Duration: 04 Mar 2023 → 06 Mar 2023 |
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- Emulating a target trial of second-line anti-diabetic drugs use and risk of major adverse cardiovascular events
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