Abstract
AimsTo 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.MethodsThis 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.ResultsThe 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.ConclusionsCompared 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.
Highlights
Randomised controlled trials indicate that sodium-glucose co-transporter 2 inhibitors (SGLT2i) may reduce the risk of cardiovascular and renal events in patients with type 2 diabetes [1,2,3,4,5,6]
We identified 10,842 new users of dipeptidyl peptidase-4 inhibitors (DPP-4i) or SGLT2i from 30 June 2014 to 30 June 2018
Our study cohort consisted of 2,939 new users of SGLT2i and 2,939 new users of DPP-4i
Summary
Randomised controlled trials indicate that sodium-glucose co-transporter 2 inhibitors (SGLT2i) may reduce the risk of cardiovascular and renal events in patients with type 2 diabetes [1,2,3,4,5,6]. Studies using dipeptidyl peptidase-4 inhibitors (DPP-4i) as a comparator showed conflicting findings [8, 10,11,12,13] These conflicting results could be due to differences in study design and exclusion criteria, such as the exclusion of patients at higher risk of amputation (e.g. those treated with insulin at baseline or with a history of amputation). These studies included a large number of real-world patients with type 2 diabetes, the relatively short follow-up of less than 1 year may have precluded estimation of potential longterm effects of SGLT2i on the incidence of LEA. Of the SGLT2i drug class, only empagliflozin and dapagliflozin were available in Slovenia during the data analysis period of this study
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