Effect of pharmacological selectivity of SGLT2 inhibitors on cardiovascular outcomes in patients with type 2 diabetes: a meta-analysis
Abstract Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce major adverse cardiovascular events (MACE) in type 2 diabetic (T2DM) patients. Pharmacological selectivity of these agents to SGLT2 over SGLT1 is highly variant, with unknown clinical relevance. Genetically reduced SGLT1—but not SGLT2...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-52331-w |
| _version_ | 1827329219383787520 |
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| author | Alex Ali Sayour Attila Oláh Mihály Ruppert Bálint András Barta Béla Merkely Tamás Radovits |
| author_facet | Alex Ali Sayour Attila Oláh Mihály Ruppert Bálint András Barta Béla Merkely Tamás Radovits |
| author_sort | Alex Ali Sayour |
| collection | DOAJ |
| description | Abstract Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce major adverse cardiovascular events (MACE) in type 2 diabetic (T2DM) patients. Pharmacological selectivity of these agents to SGLT2 over SGLT1 is highly variant, with unknown clinical relevance. Genetically reduced SGLT1—but not SGLT2—activity correlates with lower risk of heart failure and mortality, therefore additional non-selective SGLT1 inhibition might be beneficial. In this prespecified meta-analysis, we included 6 randomized, placebo-controlled cardiovascular outcome trials of SGLT2 inhibitors assessing MACE in 57,553 patients with T2DM. Mixed-effects meta-regression revealed that pharmacological selectivity of SGLT2 inhibitors (either as continuous or dichotomized variable) had no significant impact on most outcomes. However, lower SGLT2 selectivity correlated with significantly lower risk of stroke (pseudo-R2 = 78%; p = 0.011). Indeed, dual SGLT1/2 inhibitors significantly reduced the risk of stroke (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.64–0.94), unlike selective agents (p for interaction = 0.018). The risk of diabetic ketoacidosis and genital infections was higher in both pharmacological groups versus placebo. However, hypotension occurred more often with non-selective SGLT2 inhibitors (odds ratio [OR], 1.87; 95% CI, 1.20–2.92) compared with selective agents (p for interaction = 0.044). In conclusion, dual SGLT1/2 inhibition reduces stroke in high-risk T2DM patients but has limited additional effect on other clinical outcomes. |
| first_indexed | 2024-03-07T15:29:41Z |
| format | Article |
| id | doaj.art-62b324179c574278b916692e29fce7f8 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:29:41Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-62b324179c574278b916692e29fce7f82024-03-05T16:29:14ZengNature PortfolioScientific Reports2045-23222024-01-011411910.1038/s41598-024-52331-wEffect of pharmacological selectivity of SGLT2 inhibitors on cardiovascular outcomes in patients with type 2 diabetes: a meta-analysisAlex Ali Sayour0Attila Oláh1Mihály Ruppert2Bálint András Barta3Béla Merkely4Tamás Radovits5Heart and Vascular Center, Department of Cardiology, Semmelweis UniversityHeart and Vascular Center, Department of Cardiology, Semmelweis UniversityHeart and Vascular Center, Department of Cardiology, Semmelweis UniversityHeart and Vascular Center, Department of Cardiology, Semmelweis UniversityHeart and Vascular Center, Department of Cardiology, Semmelweis UniversityHeart and Vascular Center, Department of Cardiology, Semmelweis UniversityAbstract Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce major adverse cardiovascular events (MACE) in type 2 diabetic (T2DM) patients. Pharmacological selectivity of these agents to SGLT2 over SGLT1 is highly variant, with unknown clinical relevance. Genetically reduced SGLT1—but not SGLT2—activity correlates with lower risk of heart failure and mortality, therefore additional non-selective SGLT1 inhibition might be beneficial. In this prespecified meta-analysis, we included 6 randomized, placebo-controlled cardiovascular outcome trials of SGLT2 inhibitors assessing MACE in 57,553 patients with T2DM. Mixed-effects meta-regression revealed that pharmacological selectivity of SGLT2 inhibitors (either as continuous or dichotomized variable) had no significant impact on most outcomes. However, lower SGLT2 selectivity correlated with significantly lower risk of stroke (pseudo-R2 = 78%; p = 0.011). Indeed, dual SGLT1/2 inhibitors significantly reduced the risk of stroke (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.64–0.94), unlike selective agents (p for interaction = 0.018). The risk of diabetic ketoacidosis and genital infections was higher in both pharmacological groups versus placebo. However, hypotension occurred more often with non-selective SGLT2 inhibitors (odds ratio [OR], 1.87; 95% CI, 1.20–2.92) compared with selective agents (p for interaction = 0.044). In conclusion, dual SGLT1/2 inhibition reduces stroke in high-risk T2DM patients but has limited additional effect on other clinical outcomes.https://doi.org/10.1038/s41598-024-52331-w |
| spellingShingle | Alex Ali Sayour Attila Oláh Mihály Ruppert Bálint András Barta Béla Merkely Tamás Radovits Effect of pharmacological selectivity of SGLT2 inhibitors on cardiovascular outcomes in patients with type 2 diabetes: a meta-analysis Scientific Reports |
| title | Effect of pharmacological selectivity of SGLT2 inhibitors on cardiovascular outcomes in patients with type 2 diabetes: a meta-analysis |
| title_full | Effect of pharmacological selectivity of SGLT2 inhibitors on cardiovascular outcomes in patients with type 2 diabetes: a meta-analysis |
| title_fullStr | Effect of pharmacological selectivity of SGLT2 inhibitors on cardiovascular outcomes in patients with type 2 diabetes: a meta-analysis |
| title_full_unstemmed | Effect of pharmacological selectivity of SGLT2 inhibitors on cardiovascular outcomes in patients with type 2 diabetes: a meta-analysis |
| title_short | Effect of pharmacological selectivity of SGLT2 inhibitors on cardiovascular outcomes in patients with type 2 diabetes: a meta-analysis |
| title_sort | effect of pharmacological selectivity of sglt2 inhibitors on cardiovascular outcomes in patients with type 2 diabetes a meta analysis |
| url | https://doi.org/10.1038/s41598-024-52331-w |
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