Sex-Based Differences in SGLT2i and GLP-1RA Use and Mortality in T2DM with Atherosclerotic Cardiovascular Disease
Abstract
1. Introduction
2. Material and Methods
2.1. Study Population
2.2. Statistical Analysis
3. Results
3.1. Study Population Characteristics
3.2. Cardioprotective Medication Dispensing Rates
3.3. Survival and Mortality Rates by Gender
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations and Acronyms
| SGLT2i | Sodium-glucose cotransporter-2 inhibitor |
| GLP-1RA | Glucagon-like peptide-1 receptor agonist |
| T2DM | Type 2 diabetes mellitus |
| ASCVD | Atherosclerotic cardiovascular disease |
| HF | Heart failure |
| CVA | Cerebrovascular accident |
| TIA | Transient ischemic attack |
References
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| Treatment Group | Overall | Female | Male | p-Value |
|---|---|---|---|---|
| n | 138,397 | 55,828 (40.3%) | 82,569 (59.7%) | |
| Age, years (mean ± SD) | 72 ± 11 | 75 ± 11 | 71 ± 11 | <0.001 |
| Age Group, n (%) | <0.001 | |||
| 19–60 | 20,632 (14.9) | 5589 (10) | 15,043 (18.2) | |
| 61–74 | 57,738 (41.7) | 20,233 (36.2) | 37,505 (45.4) | |
| 75+ | 60,027 (43.4) | 30,006 (53.7) | 30,021 (36.4) | |
| Sector, n (%) | 0.060 | |||
| Arab | 24,035 (17.4) | 9560 (17.1) | 14,475 (17.5) | |
| General population | 114,362 (82.6) | 46,268 (82.9) | 68,094 (82.5) | |
| Periphery residence, n (%) | 7138 (5.2) | 2844 (5.1) | 4294 (5.2) | 0.380 |
| Cardiovascular risk factors: | ||||
| Obesity, n (%) | 86,583 (62.6) | 39,527 (70.8) | 47,056 (57) | <0.001 |
| BMI (mean ± SD) | 29.7 ± 5.5 | 30.8 ± 6.2 | 29.0 ± 4.8 | <0.001 |
| Dyslipidemia, n (%) | 97,351 (70.3) | 39,108 (70.1) | 58,243 (70.5) | 0.051 |
| Hypertension, n (%) | 123,633 (89.3) | 51,562 (92.4) | 72,071 (87.3) | <0.001 |
| CKD, n (%) | 24,123 (17.4) | 8409 (15.1) | 15,714 (19.0) | <0.001 |
| Smokers, n (%) | 67,823 (49.3) | 15,448 (27.9) | 52,375 (63.7) | <0.001 |
| Cardiovascular disease: | ||||
| IHD, n (%) | 100,328 (72.5) | 35,813 (64.1) | 64,515 (78.1) | <0.001 |
| CVA/TIA, n (%) | 51,329 (37.1) | 73,702 (42.5) | 27,627 (33.5) | <0.001 |
| PVD, n (%) | 19,665 (14.2) | 6.795 (12.2) | 12,870 (15.6) | <0.001 |
| Heart Failure, n (%) | 39,179 (28.3) | 16,230 (29.1) | 22,949 (27.8) | <0.001 |
| Laboratory Parameters | ||||
| LDL-C, mg/dL (mean ± SD) | 95 ± 35 | 97 ± 35 | 94 ± 35 | <0.001 |
| HDL-C, mg/dL (mean ± SD) | 44 ± 11 | 49 ± 12 | 41 ± 10 | <0.001 |
| Total Cholesterol, mg/dL (mean ± SD) | 173 ± 45 | 179 ± 44 | 169 ± 45 | <0.001 |
| Triglycerides, mg/dL, (mean ± SD) | 166 ± 122 | 160 ± 96 | 170 ± 137 | <0.001 |
| Treatment Group | Overall | Female | Male | p-Value |
|---|---|---|---|---|
| n | 138,397 | 55,828 | 82,569 | |
| SGLT2i and GLP-1RA | ||||
| SGLT2i, n (%) | 51,279 (37.1) | 15,509 (27.8) | 35,770 (43.3) | <0.001 |
| GLP-1RA, n (%) | 32,404 (23.4) | 11,874 (21.3) | 20,530 (24.9) | <0.001 |
| Other Medications: | ||||
| Statins, n (%) | 131,150 (94.8) | 52,878 (94.7) | 78,272 (94.8) | 0.512 |
| Aspirin, n (%) | 127,855 (92.4) | 51,056 (91.5) | 76,799 (93) | <0.001 |
| Clopidogrel, n (%) | 58,931 (42.6) | 19,436 (34.8) | 39,495 (47.8) | <0.001 |
| Prasugrel, n (%) | 4233 (3.1) | 730 (1.3) | 3503 (4.2) | <0.001 |
| Ticagrelor, n (%) | 6145 (4.4) | 1550 (2.8) | 4595 (5.6) | <0.001 |
| Ezetimibe, n (%) | 15,071 (10.9) | 5852 (10.5) | 9219 (11.2) | <0.001 |
| ACEi/ARB, n (%) | 120,414 (87.0) | 49,170 (88.1) | 71,244 (86.3) | <0.001 |
| Beta-blockers, n (%) | 109,432 (79.1) | 45,277 (81.1) | 64,155 (77.7) | <0.001 |
| MRA, n (%) | 22,355 (16.2) | 9705 (17.4) | 12,650 (15.3) | <0.001 |
| Other anti-diabetes drugs *, n (%) | 122,056 (88.2) | 49,288 (88.3) | 72,768 (88.1) | 0.379 |
| Characteristic | HR 1 | 95% CI 1 | p-Value |
|---|---|---|---|
| gender | |||
| Female | — | ||
| Male | 1.009 | 0.989, 1.030 | 0.3650 |
| Age Group | |||
| 19–60 | — | ||
| 61–74 | 1.694 | 1.622, 1.768 | <0.001 |
| 75+ | 3.284 | 3.147, 3.427 | <0.001 |
| Smoking | 1.100 | 1.079, 1.122 | <0.001 |
| Hypertension | 1.160 | 1.113, 1.210 | <0.001 |
| CVA/TIA | 1.331 | 1.305, 1.358 | <0.001 |
| Chronic Kidney Disease | 1.593 | 1.560, 1.626 | <0.001 |
| PVD | 1.349 | 1.318, 1.380 | <0.001 |
| GLP-1RA | 0.466 | 0.451, 0.482 | <0.001 |
| SGLT2i | 0.307 | 0.299, 0.316 | <0.001 |
| ACEi/ARB | 0.969 | 0.951, 0.987 | 0.009 |
| Statins | 0.827 | 0.792, 0.864 | <0.001 |
| Ezecor | 0.843 | 0.817, 0.870 | <0.001 |
| Aspirin | 0.895 | 0.861, 0.931 | <0.001 |
| Effient | 0.851 | 0.792, 0.914 | <0.001 |
| Brilinta | 0.867 | 0.825, 0.911 | <0.001 |
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Vaknin-Assa, H.; Wolf, A.; Hilu, R.; Giladi, E.; Gabarin, M.; Losin, I.; Arnson, Y.; Pereg, D.; Assali, A.; Arow, Z. Sex-Based Differences in SGLT2i and GLP-1RA Use and Mortality in T2DM with Atherosclerotic Cardiovascular Disease. Biomedicines 2026, 14, 404. https://doi.org/10.3390/biomedicines14020404
Vaknin-Assa H, Wolf A, Hilu R, Giladi E, Gabarin M, Losin I, Arnson Y, Pereg D, Assali A, Arow Z. Sex-Based Differences in SGLT2i and GLP-1RA Use and Mortality in T2DM with Atherosclerotic Cardiovascular Disease. Biomedicines. 2026; 14(2):404. https://doi.org/10.3390/biomedicines14020404
Chicago/Turabian StyleVaknin-Assa, Hana, Ammie Wolf, Ranin Hilu, Ela Giladi, Mustafa Gabarin, Ilya Losin, Yoav Arnson, David Pereg, Abid Assali, and Ziad Arow. 2026. "Sex-Based Differences in SGLT2i and GLP-1RA Use and Mortality in T2DM with Atherosclerotic Cardiovascular Disease" Biomedicines 14, no. 2: 404. https://doi.org/10.3390/biomedicines14020404
APA StyleVaknin-Assa, H., Wolf, A., Hilu, R., Giladi, E., Gabarin, M., Losin, I., Arnson, Y., Pereg, D., Assali, A., & Arow, Z. (2026). Sex-Based Differences in SGLT2i and GLP-1RA Use and Mortality in T2DM with Atherosclerotic Cardiovascular Disease. Biomedicines, 14(2), 404. https://doi.org/10.3390/biomedicines14020404

