Cardiovascular Risks With SGLT2 Inhibitors in Clinical Practice Among Patients With Type 2 Diabetes
Hsuan-Yu Su1, Chen-Yi Yang1, Yu-Hsuan Lee1
1Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Importance:
Cardiovascular disease (CVD) can be recurrent during type 2 diabetes (T2D) progression in this aging population. The effectiveness of sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy on total (ie, first and subsequent) CVD among patients with T2D in clinical practice remains uncertain.
Objective:
To analyze the comparative association of SGLT2i vs dipeptidyl peptidase 4 inhibitor (DPP4i) therapy with total CVD among patients with T2D in clinical practice.
Design, Setting, And Participants:
This retrospective cohort study used electronic medical records at the National Cheng Kung University Hospital, a leading medical center in Taiwan, from 2015 through 2021. Adult patients with T2D who initiated first use of the study drugs from 2016 through 2019, with up to 6 years of follow-up, were identified.
Main Outcomes And Measures:
The primary outcomes included total composite CVD events and individual CVD subtypes (ie, atrial fibrillation, coronary heart disease, heart failure, stroke, myocardial infarction, and transient ischemic attack). A shared frailty model analysis was used to assess the association of treatment with repeat CVD events. Data from patients at high risk for CVD recurrence were further analyzed. Data were analyzed from September 1, 2022, to December 31, 2023.
Results:
Overall, 8384 patients with T2D were identified (mean [SD] age, 63.7 [12.4] years; 4645 [55.4%] male). A total of 1632 propensity score-matched pairs of SGLT2i (mean [SD] age, 57.8 [12.0] years; 673 [41.2%] female and 959 [58.8%] male) and DPP4i (mean [SD] age, 58.2 [12.9] years; 655 [40.1%] female and 977 [59.9%] male) users were included. SGLT2i was associated with reduced total CVD risk vs DPP4i therapy (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98]) but not the first CVD event (with the use of SGLT2i therapy were more prominent for patients at high risk of CVD (ie, HR, 0.70 [95% CI, 0.62-0.80] for individuals with estimated glomerular filtration rate lower than 60 mL/min/1.73 m2; HR, 0.70 [95% CI, 0.64-0.78]; for individuals having any diabetes-related complications; and HR, 0.72 [95% CI, 0.65-0.80] for individuals with a history of CVD) compared with the overall cohort. Among patients at high risk of CVD, greater reduced total CVD burden associated with SGLT2i therapy was observed for women vs men (eg, HR, 0.59 [95% CI, 0.49-0.72] in the subgroup with CVD history).
Conclusions And Relevance:
In this cohort study of patients with T2D, the use of SGLT2is vs DPP4is was associated with reduced total cardiovascular burden, suggesting that long-term use of this therapy may optimize treatment benefit among patients with chronic CVD. The SGLT2i-associated benefit among patients with high risk of CVD encourages the prioritization of SGLT2i use for these vulnerable individuals.
Insights
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduced total cardiovascular disease (CVD) events in type 2 diabetes (T2D) patients compared to dipeptidyl peptidase 4 inhibitors (DPP4i). Benefits were most pronounced in high-risk patients, particularly women, suggesting SGLT2i prioritization for vulnerable individuals.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Cardiovascular disease (CVD) recurrence is a significant concern in aging populations with type 2 diabetes (T2D).
- The comparative effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) versus dipeptidyl peptidase 4 inhibitors (DPP4i) for total CVD events in T2D patients in clinical practice is not well-established.
Purpose of the Study:
- To compare the association of SGLT2i therapy versus DPP4i therapy with total CVD events in patients with T2D.
- To evaluate the effectiveness of SGLT2i in reducing both first and subsequent CVD events.
Main Methods:
- A retrospective cohort study utilizing electronic medical records from a leading Taiwanese hospital (2015-2021).
- Included adult T2D patients initiating SGLT2i or DPP4i therapy (2016-2019) with up to 6 years of follow-up.
- Propensity score matching and shared frailty models were used to analyze total composite CVD events and subtypes, including repeat events.
Main Results:
- SGLT2i therapy was associated with a reduced risk of total CVD events compared to DPP4i therapy (HR, 0.82; 95% CI, 0.69-0.98).
- This benefit was more significant in high-risk T2D patients, including those with estimated glomerular filtration rate <60 mL/min/1.73 m², diabetes-related complications, or a history of CVD.
- Among high-risk patients, SGLT2i showed a greater reduction in total CVD burden for women compared to men, especially those with a history of CVD.
Conclusions:
- SGLT2i therapy is associated with a reduced total cardiovascular burden in T2D patients compared to DPP4i therapy.
- Long-term SGLT2i use may optimize treatment benefits for patients with chronic CVD.
- Prioritizing SGLT2i use for high-risk T2D individuals, particularly women, is encouraged due to observed benefits in reducing CVD recurrence.
Related Concept Videos
01:22Diabetes Mellitus: Type 2 and Gestational
01:26Oral Hypoglycemic Agents: Biguanides and Glitazones
01:23Dipeptidyl Peptidase 4 Inhibitors
01:27Glucose Transporters
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
01:15Diabetes: Symptoms, Diagnosis, and Complications
01:17Oral Hypoglycemic Agents: Sulfonylureas