Oriana Hoi Yun Yu1,2, Sophie Dell'Aniello1, Baiju R Shah3,4,5, Vanessa C Brunetti1,6, Jean-Marc Daigle7, Michael Fralick3,8, Antonios Douros1,9,10,11, Nianping Hu12, Silvia Alessi-Severini13,14, Anat Fisher15, Shawn C Bugden13,16, Paul E Ronksley17, Kristian B Filion1,9, Pierre Ernst1,9, Lisa M Lix. 1. Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montréal, Québec, Canada. 2. Division of Endocrinology, Department of Medicine, Jewish General Hospital, Montréal, Québec, Canada. 3. Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 4. Institute for Clinical Evaluative Sciences (ICES), Toronto, Ontario, Canada. 5. Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. 6. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Québec, Canada. 7. Institut national d'excellence en santé et en services sociaux (INESSS), Québec City, Québec, Canada. 8. Sinai Health System, Toronto, Ontario, Canada. 9. Departments of Medicine and of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montréal, Québec, Canada. 10. Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. 11. Berlin Institute of Health, Berlin, Germany. 12. The Health Quality Council, Saskatoon, Saskatchewan, Canada. 13. College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. 14. Manitoba Centre for Health Policy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. 15. Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada. 16. School of Pharmacy, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada. 17. Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Abstract
OBJECTIVE: Reports of amputations associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors have been inconsistent. We aimed to compare the risk of below-knee amputation with SGLT2 inhibitors versus dipeptidyl peptidase 4 (DPP-4) inhibitors among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This multicenter observational study used administrative health care databases from seven Canadian provinces and the U.K. Incident SGLT2 inhibitor users were matched to DPP-4 inhibitor users using a prevalent new-user design and time-conditional propensity scores. Cox proportional hazards models were used to estimate site-specific adjusted hazard ratios (HR) and corresponding 95% CIs of incident below-knee amputation for SGLT2 inhibitor versus DPP-4 inhibitor users. Random effects meta-analyses were used to pool the site-specific results. RESULTS: The study cohort included 207,817 incident SGLT2 inhibitor users matched to 207,817 DPP-4 inhibitor users. During a mean exposed follow-up time of 11 months, the amputation rate was 1.3 per 1,000 person-years among SGLT2 inhibitor users and 1.5 per 1,000 person-years among DPP-4 inhibitor users. The adjusted HR of below-knee amputations associated with SGLT2 inhibitor use compared with DPP-4 inhibitor use was 0.88 (95% CI 0.71-1.09). Similar results were obtained in stratified analyses by specific SGLT2 inhibitor molecule. CONCLUSIONS: In this large multicenter observational study, there was no association between SGLT2 inhibitor use and incident below-knee amputations among patients with type 2 diabetes compared with DPP-4 inhibitor use. While these findings provide some reassurance, studies with a longer duration of follow-up are needed to assess potential long-term effects.
OBJECTIVE: Reports of amputations associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors have been inconsistent. We aimed to compare the risk of below-knee amputation with SGLT2 inhibitors versus dipeptidyl peptidase 4 (DPP-4) inhibitors among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This multicenter observational study used administrative health care databases from seven Canadian provinces and the U.K. Incident SGLT2 inhibitor users were matched to DPP-4 inhibitor users using a prevalent new-user design and time-conditional propensity scores. Cox proportional hazards models were used to estimate site-specific adjusted hazard ratios (HR) and corresponding 95% CIs of incident below-knee amputation for SGLT2 inhibitor versus DPP-4 inhibitor users. Random effects meta-analyses were used to pool the site-specific results. RESULTS: The study cohort included 207,817 incident SGLT2 inhibitor users matched to 207,817 DPP-4 inhibitor users. During a mean exposed follow-up time of 11 months, the amputation rate was 1.3 per 1,000 person-years among SGLT2 inhibitor users and 1.5 per 1,000 person-years among DPP-4 inhibitor users. The adjusted HR of below-knee amputations associated with SGLT2 inhibitor use compared with DPP-4 inhibitor use was 0.88 (95% CI 0.71-1.09). Similar results were obtained in stratified analyses by specific SGLT2 inhibitor molecule. CONCLUSIONS: In this large multicenter observational study, there was no association between SGLT2 inhibitor use and incident below-knee amputations among patients with type 2 diabetes compared with DPP-4 inhibitor use. While these findings provide some reassurance, studies with a longer duration of follow-up are needed to assess potential long-term effects.
Authors: Elisabetta Patorno; Ajinkya Pawar; Lily G Bessette; Dae H Kim; Chintan Dave; Robert J Glynn; Medha N Munshi; Sebastian Schneeweiss; Deborah J Wexler; Seoyoung C Kim Journal: Diabetes Care Date: 2021-01-25 Impact factor: 19.112
Authors: Lisa M Lix; Shamsia Sobhan; Audray St-Jean; Jean-Marc Daigle; Anat Fisher; Oriana H Y Yu; Sophie Dell'Aniello; Nianping Hu; Shawn C Bugden; Baiju R Shah; Paul E Ronksley; Silvia Alessi-Severini; Antonios Douros; Pierre Ernst; Kristian B Filion Journal: BMC Health Serv Res Date: 2021-07-31 Impact factor: 2.655