Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non-SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: A real-world meta-analysis of 4 observational databases (OBSERVE-4D).
AIMS
Sodium glucose co-transporter 2 inhibitors (SGLT2i) are indicated for treatment of type 2 diabetes mellitus (T2DM); some SGLT2i have reported cardiovascular benefit, and some have reported risk of below-knee lower extremity (BKLE) amputation. This study examined the real-world comparative effectiveness within the SGLT2i class and compared with non-SGLT2i antihyperglycaemic agents.


MATERIALS AND METHODS
Data from 4 large US administrative claims databases were used to characterize risk and provide population-level estimates of canagliflozin's effects on hospitalization for heart failure (HHF) and BKLE amputation vs other SGLT2i and non-SGLT2i in T2DM patients. Comparative analyses using a propensity score-adjusted new-user cohort design examined relative hazards of outcomes across all new users and a subpopulation with established cardiovascular disease.


RESULTS
Across the 4 databases (142 800 new users of canagliflozin, 110 897 new users of other SGLT2i, 460 885 new users of non-SGLT2i), the meta-analytic hazard ratio estimate for HHF with canagliflozin vs non-SGLT2i was 0.39 (95% CI, 0.26-0.60) in the on-treatment analysis. The estimate for BKLE amputation with canagliflozin vs non-SGLT2i was 0.75 (95% CI, 0.40-1.41) in the on-treatment analysis and 1.01 (95% CI, 0.93-1.10) in the intent-to-treat analysis. Effects in the subpopulation with established cardiovascular disease were similar for both outcomes. No consistent differences were observed between canagliflozin and other SGLT2i.


CONCLUSIONS
In this large comprehensive analysis, canagliflozin and other SGLT2i demonstrated HHF benefits consistent with clinical trial data, but showed no increased risk of BKLE amputation vs non-SGLT2i. HHF and BKLE amputation results were similar in the subpopulation with established cardiovascular disease. This study helps further characterize the potential benefits and harms of SGLT2i in routine clinical practice to complement evidence from clinical trials and prior observational studies.
['Ryan|Patrick B|PB|0000-0002-9727-2138', 'Buse|John B|JB|0000-0002-9723-3876', 'Schuemie|Martijn J|MJ|0000-0002-0817-5361', 'DeFalco|Frank|F|', 'Yuan|Zhong|Z|0000-0002-5824-2040', 'Stang|Paul E|PE|0000-0002-9528-9657', 'Berlin|Jesse A|JA|0000-0002-9810-745X', 'Rosenthal|Norman|N|']
D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D000671:Amputation D000068896:Canagliflozin D019992:Databases as Topic D003924:Diabetes Mellitus, Type 2 D003925:Diabetic Angiopathies D017719:Diabetic Foot D005260:Female D006333:Heart Failure D006760:Hospitalization D006801:Humans D008297:Male D008875:Middle Aged D064887:Observational Studies as Topic D012189:Retrospective Studies D012307:Risk Factors D000077203:Sodium-Glucose Transporter 2 Inhibitors D016896:Treatment Outcome D055815:Young Adult
SGLT2 inhibitor type 2 diabetes