Sodium-glucose cotransporter 2 inhibitors and cardiovascular events among patients with type 2 diabetes and low-to-normal body mass index: a nationwide cohort study
Abstract Background Patients with low-to-normal body mass index (BMI; < 25.0 kg/m2) were underrepresented in major randomized controlled trials on sodium-glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes. The present study aims to investigate the effectiveness of SGLT2 inhibitors for...
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BMC
2024-10-01
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| Series: | Cardiovascular Diabetology |
| Online Access: | https://doi.org/10.1186/s12933-024-02478-7 |
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| author | Yuichiro Mori Toshiaki Komura Motohiko Adomi Ryuichiro Yagi Shingo Fukuma Naoki Kondo Motoko Yanagita O. Kenrik Duru Katherine R. Tuttle Kosuke Inoue |
| author_facet | Yuichiro Mori Toshiaki Komura Motohiko Adomi Ryuichiro Yagi Shingo Fukuma Naoki Kondo Motoko Yanagita O. Kenrik Duru Katherine R. Tuttle Kosuke Inoue |
| author_sort | Yuichiro Mori |
| collection | DOAJ |
| description | Abstract Background Patients with low-to-normal body mass index (BMI; < 25.0 kg/m2) were underrepresented in major randomized controlled trials on sodium-glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes. The present study aims to investigate the effectiveness of SGLT2 inhibitors for cardiovascular outcomes among patients with type 2 diabetes and low-to-normal BMI, using finer stratification than previous trials. Methods This cohort study with a target trial emulation framework was conducted using insurance claims and health screening records of more than 30 million working-age citizens in Japan acquired from April 1, 2015 to March 31, 2022. 139,783 new users of SGLT2 inhibitors matched to 139,783 users of dipeptidyl protease (DPP) 4 inhibitors with stratification by BMI category (< 20.0, 20.0–22.4, 22.5–24.9, 25.0–29.9, 30.0–34.9, and 35.0 ≤ kg/m2). The primary outcome was a composite of all-cause death, myocardial infarction, stroke, or heart failure. Secondary outcomes were the components of the primary outcome. Cox proportional hazard models were used to compare SGLT2 inhibitors with DPP4 inhibitors in the whole population and subgroups defined by the BMI category. Results Among participants, 17.3% (n = 48,377) were female and 31.0% (n = 86,536) had low-to-normal BMI (< 20.0 kg/m2, 1.9% [n = 5,350]; 20.0–22.4 kg/m2, 8.5% [n = 23,818]; and 22.5–24.9 kg/m2, 20.5% [n = 57,368]). Over a median follow-up of 24 months, the primary outcome occurred in 2.9% (n = 8,165) of participants. SGLT2 inhibitors were associated with a decreased incidence of the primary outcome in the whole population (HR [95%CI] = 0.92 [0.89 to 0.96]), but not in patients with low-to-normal BMI (< 20.0 kg/m2, HR [95%CI] = 1.08 [0.80 to 1.46]; 20.0–22.4 kg/m2, HR [95%CI] = 1.04 [0.90 to 1.20]; and 22.5–24.9 kg/m2, HR [95%CI] = 0.92 [0.84 to 1.01]). Conclusions The protective effect of SGLT2 inhibitors on cardiovascular events among patients with type 2 diabetes appeared to decrease with lower BMI and was not significant among patients with low-to-normal BMI (< 25.0 kg/m2). These findings suggest the importance of considering BMI when initiating SGLT2 inhibitors. Graphical abstract |
| format | Article |
| id | doaj-art-bcd41e39ee9544bb85db4c1b289913d3 |
| institution | OA Journals |
| issn | 1475-2840 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMC |
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| series | Cardiovascular Diabetology |
| spelling | doaj-art-bcd41e39ee9544bb85db4c1b289913d32025-08-20T02:11:23ZengBMCCardiovascular Diabetology1475-28402024-10-0123111010.1186/s12933-024-02478-7Sodium-glucose cotransporter 2 inhibitors and cardiovascular events among patients with type 2 diabetes and low-to-normal body mass index: a nationwide cohort studyYuichiro Mori0Toshiaki Komura1Motohiko Adomi2Ryuichiro Yagi3Shingo Fukuma4Naoki Kondo5Motoko Yanagita6O. Kenrik Duru7Katherine R. Tuttle8Kosuke Inoue9Department of Human Health Sciences, Graduate School of Medicine, Kyoto UniversityDepartment of Epidemiology, Boston University School of Public HealthDepartment of Epidemiology, Harvard T.H. Chan School of Public HealthDivision of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s HospitalDepartment of Human Health Sciences, Graduate School of Medicine, Kyoto UniversityDepartment of Social Epidemiology, Graduate School of Medicine, Kyoto UniversityDepartment of Nephrology, Graduate School of Medicine, Kyoto UniversityDivision of General Internal Medicine and Health Services Research, David Geffen School of Medicine at UCLAKidney Research Institute, University of WashingtonDepartment of Social Epidemiology, Graduate School of Medicine, Kyoto UniversityAbstract Background Patients with low-to-normal body mass index (BMI; < 25.0 kg/m2) were underrepresented in major randomized controlled trials on sodium-glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes. The present study aims to investigate the effectiveness of SGLT2 inhibitors for cardiovascular outcomes among patients with type 2 diabetes and low-to-normal BMI, using finer stratification than previous trials. Methods This cohort study with a target trial emulation framework was conducted using insurance claims and health screening records of more than 30 million working-age citizens in Japan acquired from April 1, 2015 to March 31, 2022. 139,783 new users of SGLT2 inhibitors matched to 139,783 users of dipeptidyl protease (DPP) 4 inhibitors with stratification by BMI category (< 20.0, 20.0–22.4, 22.5–24.9, 25.0–29.9, 30.0–34.9, and 35.0 ≤ kg/m2). The primary outcome was a composite of all-cause death, myocardial infarction, stroke, or heart failure. Secondary outcomes were the components of the primary outcome. Cox proportional hazard models were used to compare SGLT2 inhibitors with DPP4 inhibitors in the whole population and subgroups defined by the BMI category. Results Among participants, 17.3% (n = 48,377) were female and 31.0% (n = 86,536) had low-to-normal BMI (< 20.0 kg/m2, 1.9% [n = 5,350]; 20.0–22.4 kg/m2, 8.5% [n = 23,818]; and 22.5–24.9 kg/m2, 20.5% [n = 57,368]). Over a median follow-up of 24 months, the primary outcome occurred in 2.9% (n = 8,165) of participants. SGLT2 inhibitors were associated with a decreased incidence of the primary outcome in the whole population (HR [95%CI] = 0.92 [0.89 to 0.96]), but not in patients with low-to-normal BMI (< 20.0 kg/m2, HR [95%CI] = 1.08 [0.80 to 1.46]; 20.0–22.4 kg/m2, HR [95%CI] = 1.04 [0.90 to 1.20]; and 22.5–24.9 kg/m2, HR [95%CI] = 0.92 [0.84 to 1.01]). Conclusions The protective effect of SGLT2 inhibitors on cardiovascular events among patients with type 2 diabetes appeared to decrease with lower BMI and was not significant among patients with low-to-normal BMI (< 25.0 kg/m2). These findings suggest the importance of considering BMI when initiating SGLT2 inhibitors. Graphical abstracthttps://doi.org/10.1186/s12933-024-02478-7 |
| spellingShingle | Yuichiro Mori Toshiaki Komura Motohiko Adomi Ryuichiro Yagi Shingo Fukuma Naoki Kondo Motoko Yanagita O. Kenrik Duru Katherine R. Tuttle Kosuke Inoue Sodium-glucose cotransporter 2 inhibitors and cardiovascular events among patients with type 2 diabetes and low-to-normal body mass index: a nationwide cohort study Cardiovascular Diabetology |
| title | Sodium-glucose cotransporter 2 inhibitors and cardiovascular events among patients with type 2 diabetes and low-to-normal body mass index: a nationwide cohort study |
| title_full | Sodium-glucose cotransporter 2 inhibitors and cardiovascular events among patients with type 2 diabetes and low-to-normal body mass index: a nationwide cohort study |
| title_fullStr | Sodium-glucose cotransporter 2 inhibitors and cardiovascular events among patients with type 2 diabetes and low-to-normal body mass index: a nationwide cohort study |
| title_full_unstemmed | Sodium-glucose cotransporter 2 inhibitors and cardiovascular events among patients with type 2 diabetes and low-to-normal body mass index: a nationwide cohort study |
| title_short | Sodium-glucose cotransporter 2 inhibitors and cardiovascular events among patients with type 2 diabetes and low-to-normal body mass index: a nationwide cohort study |
| title_sort | sodium glucose cotransporter 2 inhibitors and cardiovascular events among patients with type 2 diabetes and low to normal body mass index a nationwide cohort study |
| url | https://doi.org/10.1186/s12933-024-02478-7 |
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