Dataset Information

Risk of lower extremity amputations in patients with type 2 diabetes using sodium-glucose co-transporter 2 inhibitors.

ABSTRACT:

Aims

To compare the influence of sodium-glucose co-transporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) on the risk of lower extremity amputations in patients with type 2 diabetes in Slovenia.

Methods

This retrospective cohort study included patients aged 40 years or more who were administered a newly introduced SGLT2i or DPP-4i between June 2014 and June 2018. Patients treated with insulin at baseline and patients with a history of amputation were excluded. Patients were matched in a 1:1 ratio using propensity score matching. Survival analysis was performed; hazard ratio (HR) and ratios of cumulative hazards at 1, 2, 3, and 4 years were estimated. On-treatment and intention-to-treat approaches were used.

Results

The study cohort (mean age: 64 years) consisted of 2,939 new users of SGLT2i (empagliflozin, 59%; dapagliflozin, 41%) matched to 2,939 new users of DPP-4i. In the on-treatment analysis (median follow-up of 2 years), the incidence of amputations was higher in SGLT2i than in DPP-4i users (4.2 vs. 2.7 per 1,000 patient years), resulting in a HR of 1.58 (95% CI 0.85-2.92; p = 0.145). An intention-to-treat analysis yielded to similar HR of 1.86 (95% CI: 1.10-3.14; p = 0.020). There was no difference in amputation rates in the first two years, but SGLT2i users had a 2.81-fold higher (95% CI: 1.63-4.84; p = 0.007) cumulative hazard of amputation at 4 years than did DPP-4i users.

Conclusions

Compared with DPP-4i use, SGLT2i use did not result in a statistically significant higher overall risk of lower extremity amputations. However, the results suggest that SGLT2i may increase the risk of amputation with long-term use.

SUBMITTER: Zerovnik S

PROVIDER: S-EPMC8841312 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Risk of lower extremity amputations in patients with type 2 diabetes using sodium-glucose co-transporter 2 inhibitors.

Zerovnik Spela S Kos Mitja M Locatelli Igor I

Acta diabetologica 20211005 2

<h4>Aims</h4>To compare the influence of sodium-glucose co-transporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) on the risk of lower extremity amputations in patients with type 2 diabetes in Slovenia.<h4>Methods</h4>This retrospective cohort study included patients aged 40 years or more who were administered a newly introduced SGLT2i or DPP-4i between June 2014 and June 2018. Patients treated with insulin at baseline and patients with a history of amputation were excl ...[more]

PMID: 34609620

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Project description:ImportanceResults of clinical trials suggest that canagliflozin, a sodium-glucose cotransporter 2 (SGLT-2) inhibitor for treating type 2 diabetes, may be associated with lower extremity amputation.ObjectiveTo quantify the association between the use of oral medication for type 2 diabetes and 5 outcomes (lower extremity amputation, peripheral arterial disease, critical limb ischemia, osteomyelitis, and ulcer).Design, setting, and participantsA retrospective cohort study was conducted using Truven Health MarketScan Commercial Claims and Encounters data on new users between September 1, 2012, and September 30, 2015. The study focused on 2.0 million commercially insured individuals and used propensity score weighting to balance baseline differences among groups. Sensitivity analyses varied statistical models, assessed the effect of combining dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists as a single referent group, adjusted for baseline use of older oral agents, and included people with baseline amputation.ExposuresNew use of SGLT-2 inhibitors alone, DPP-4 inhibitors alone, GLP-1 agonists alone, or other antidiabetic agents (sulfonylurea, metformin hydrochloride, or thiazolidinediones).Main outcomes and measuresFoot and leg amputation, defined by validated International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes.ResultsAmong 2.0 million potentially eligible individuals, a total of 953 906 (516 046 women and 437 860 men; mean [SD] age, 51.8 [10.9] years) were included in the final analyses, including 39 869 new users of SGLT-2 inhibitors (4.2%), 105 023 new users of DPP-4 inhibitors (11.0%), and 39 120 new users of GLP-1 agonists (4.1%). The median observation time ranged from 99 days for new users of GLP-1 agonists to 127 days for those using metformin, sulfonylureas, and thiazolidinediones, while the crude incident rates ranged from 4.90 per 10 000 person-years for those using metformin, sulfonylureas, and thiazolidinediones to 10.53 per 10 000 person-years for new users of SGLT-2 inhibitors. After propensity score weighting and adjustment for demographics, severity of diabetes, comorbidities, and medications, there was a nonstatistically significant increased risk of amputation associated with new use of SGLT-2 inhibitors compared with DPP-4 inhibitors (adjusted hazard ratio, 1.50; 95% CI, 0.85-2.67) and GLP-1 agonists (adjusted hazard ratio, 1.47; 95% CI, 0.64-3.36). New use of SGLT-2 inhibitors was statistically significantly associated with amputation compared with sulfonylureas, metformin, or thiazolidinediones (adjusted hazard ratio, 2.12; 95% CI, 1.19-3.77). These results persisted in sensitivity analyses.Conclusions and relevanceUse of SGLT-2 inhibitors may be associated with increased risk of amputation compared with some oral treatments for type 2 diabetes. Further observational studies are needed with extended follow-up and larger sample sizes.

Dataset Information

Risk of lower extremity amputations in patients with type 2 diabetes using sodium-glucose co-transporter 2 inhibitors.

Aims

Methods

Results

Conclusions

Publications

Risk of lower extremity amputations in patients with type 2 diabetes using sodium-glucose co-transporter 2 inhibitors.

Similar Datasets

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