Diabetes, obesity & metabolismJun 26, 2018

Comparing canagliflozin, other SGLT2 inhibitors, and non-SGLT2 drugs for heart failure hospitalizations and amputations in type 2 diabetes patients

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Apr 6, 2026

Abstract

The hazard ratio estimate for with canagliflozin vs non-SGLT2i was 0.39.

Canagliflozin is associated with a significantly lower risk of hospitalization for heart failure compared to non-SGLT2i.
The hazard ratio for below-knee lower extremity amputation with canagliflozin vs non-SGLT2i was 0.75 in the on-treatment analysis, but 1.01 in the intent-to-treat analysis.
Similar effects for hospitalization for heart failure and below-knee lower extremity amputation were observed in patients with established cardiovascular disease.
No consistent differences were noted between canagliflozin and other SGLT2i regarding these outcomes.

Simplified

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 () 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 (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.

Key numbers

0.39

Decrease in Risk

Meta-analytic hazard ratio for with canagliflozin vs non-SGLT2i

0.75

Amputation Risk

Meta-analytic hazard ratio for amputation with canagliflozin vs non-SGLT2i

142800

New Users of Canagliflozin

Total number of new users of canagliflozin across 4 databases

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Comparing canagliflozin, other SGLT2 inhibitors, and non-SGLT2 drugs for heart failure hospitalizations and amputations in type 2 diabetes patients

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