Lower-limb amputations in patients treated with SGLT2 inhibitors versus DPP-4 inhibitors: A meta-analysis of observational studies
Summary: Background: An increased risk of lower limb amputations (LLA) has been suspected with the use of sodium-glucose cotransporter type 2 inhibitors (SGLT2is) in the CANVAS programme with canagliflozin and in pharmacovigilance reports with all SGLT2is. Even if reassuring observations were repor...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-04-01
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| Series: | Diabetes Epidemiology and Management |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666970622000051 |
| _version_ | 1818206533239963648 |
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| author | Andre J. Scheen |
| author_facet | Andre J. Scheen |
| author_sort | Andre J. Scheen |
| collection | DOAJ |
| description | Summary: Background: An increased risk of lower limb amputations (LLA) has been suspected with the use of sodium-glucose cotransporter type 2 inhibitors (SGLT2is) in the CANVAS programme with canagliflozin and in pharmacovigilance reports with all SGLT2is. Even if reassuring observations were reported in several large prospective placebo-controlled cardiovascular outcome trials, real-life conditions in more frailty patients might be associated with a higher risk. Methods: This work analyses the incidence of LLA events in retrospective observational studies that compared SGLT2i users with patients treated with dipeptidyl peptidase-4 inhibitors (DPP-4is), a pharmacological class with an excellent safety profile. A meta-analysis of 12 comparative cohort studies (9 of them using a propensity score matching) worldwide has been performed. Results: The relative risk of LLA tended to be slightly lower in SGLT2i users (1228 LLA events/711159 patients) versus DPP-4i users: 2167 LLA events/1121914 patients, with a hazard ratio 0.91, 95% CI 0.85-0.98, p=0.01). However, a high between-study heterogeneity was observed (I² = 79%, P<0.00001), which could not be explained by differences across countries, between studies with/without propensity score matching, between cohorts treated with/without canagliflozin or between patients with/without peripheral artery disease. The incidence rate expressed as a number of LLA events per 1000 patient.years was almost similar among SGLT2i users and DPP-4i users (2.48±1.45 versus 2.67±3.09, p=0.849). Conclusion: Physicians should not fear an increased risk of LLA with SGLT2is compared with DPP-4is in daily clinical practice, even if caution may be advised in some patients exposed to special conditions. |
| first_indexed | 2024-12-12T04:14:32Z |
| format | Article |
| id | doaj.art-c24195b509a8441f8b1d5f210e9d9c13 |
| institution | Directory Open Access Journal |
| issn | 2666-9706 |
| language | English |
| last_indexed | 2024-12-12T04:14:32Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Diabetes Epidemiology and Management |
| spelling | doaj.art-c24195b509a8441f8b1d5f210e9d9c132022-12-22T00:38:30ZengElsevierDiabetes Epidemiology and Management2666-97062022-04-016100054Lower-limb amputations in patients treated with SGLT2 inhibitors versus DPP-4 inhibitors: A meta-analysis of observational studiesAndre J. Scheen0Department of Diabetes Nutrition and Metabolic Disorders, CHU Liège, Liège, Belgium; Division of Clinical Pharmacology, Centre for Interdisciplinary Research on Medicines (CIRM), Liège University, Liège, BelgiumSummary: Background: An increased risk of lower limb amputations (LLA) has been suspected with the use of sodium-glucose cotransporter type 2 inhibitors (SGLT2is) in the CANVAS programme with canagliflozin and in pharmacovigilance reports with all SGLT2is. Even if reassuring observations were reported in several large prospective placebo-controlled cardiovascular outcome trials, real-life conditions in more frailty patients might be associated with a higher risk. Methods: This work analyses the incidence of LLA events in retrospective observational studies that compared SGLT2i users with patients treated with dipeptidyl peptidase-4 inhibitors (DPP-4is), a pharmacological class with an excellent safety profile. A meta-analysis of 12 comparative cohort studies (9 of them using a propensity score matching) worldwide has been performed. Results: The relative risk of LLA tended to be slightly lower in SGLT2i users (1228 LLA events/711159 patients) versus DPP-4i users: 2167 LLA events/1121914 patients, with a hazard ratio 0.91, 95% CI 0.85-0.98, p=0.01). However, a high between-study heterogeneity was observed (I² = 79%, P<0.00001), which could not be explained by differences across countries, between studies with/without propensity score matching, between cohorts treated with/without canagliflozin or between patients with/without peripheral artery disease. The incidence rate expressed as a number of LLA events per 1000 patient.years was almost similar among SGLT2i users and DPP-4i users (2.48±1.45 versus 2.67±3.09, p=0.849). Conclusion: Physicians should not fear an increased risk of LLA with SGLT2is compared with DPP-4is in daily clinical practice, even if caution may be advised in some patients exposed to special conditions.http://www.sciencedirect.com/science/article/pii/S2666970622000051AmputationGliflozinMeta-analysisReal-lifeSafetySGLT2 inhibitor |
| spellingShingle | Andre J. Scheen Lower-limb amputations in patients treated with SGLT2 inhibitors versus DPP-4 inhibitors: A meta-analysis of observational studies Diabetes Epidemiology and Management Amputation Gliflozin Meta-analysis Real-life Safety SGLT2 inhibitor |
| title | Lower-limb amputations in patients treated with SGLT2 inhibitors versus DPP-4 inhibitors: A meta-analysis of observational studies |
| title_full | Lower-limb amputations in patients treated with SGLT2 inhibitors versus DPP-4 inhibitors: A meta-analysis of observational studies |
| title_fullStr | Lower-limb amputations in patients treated with SGLT2 inhibitors versus DPP-4 inhibitors: A meta-analysis of observational studies |
| title_full_unstemmed | Lower-limb amputations in patients treated with SGLT2 inhibitors versus DPP-4 inhibitors: A meta-analysis of observational studies |
| title_short | Lower-limb amputations in patients treated with SGLT2 inhibitors versus DPP-4 inhibitors: A meta-analysis of observational studies |
| title_sort | lower limb amputations in patients treated with sglt2 inhibitors versus dpp 4 inhibitors a meta analysis of observational studies |
| topic | Amputation Gliflozin Meta-analysis Real-life Safety SGLT2 inhibitor |
| url | http://www.sciencedirect.com/science/article/pii/S2666970622000051 |
| work_keys_str_mv | AT andrejscheen lowerlimbamputationsinpatientstreatedwithsglt2inhibitorsversusdpp4inhibitorsametaanalysisofobservationalstudies |