Study on SGLT2 Inhibitors and Amputation Risk

A recent study has reported no association between SGLT2 inhibitor use and incident below-knee amputations among patients with type 2 diabetes when compared with DPP-4 inhibitor use.

Oriana Hoi Yun Yu and associates from the Center for Clinical Epidemiology, Lady Davis Institute, Montréal, Canada have published the findings of the study in the journal of Diabetes Care.

Reports of amputations associated with sodium–glucose cotransporter 2 (SGLT2) inhibitors have been inconsistent. The researchers compared the risk of below-knee amputation with SGLT2 inhibitors versus dipeptidyl peptidase 4 (DPP-4) inhibitors among patients with type 2 diabetes in the instant study.

Previous reports of amputations associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors have been inconsistent. Keeping this in mind, the researchers sought to compare the risk of below-knee amputation with SGLT2 inhibitors versus dipeptidyl peptidase 4 (DPP-4) inhibitors among patients with type 2 diabetes.

The study design was a real-world multicenter observational one using administrative health care databases from seven Canadian provinces and the U.K. Incident SGLT2 inhibitor users were matched to DPP-4 inhibitor users using a prevalent new-user design and time-conditional propensity scores.

The study cohort included 207,817 incident SGLT2 inhibitor users matched to 207,817 DPP-4 inhibitor users, observed for 11 months. The primary outcome of the study was incident below-knee amputation, which investigators defined as having transtibial amputations or amputations involving the ankle and foot.

Key Findings

• The amputation rate among SGLT2 inhibitor users was 1.3 per 1000 person-years compared to 1.5 per 1000 person-years among those using DPP-4 inhibitors. Based on these results, investigators determined the corresponding hazard ratio for below-knee amputations with SGLT2 inhibitor use compared with DPP-4 inhibitor use was 0.88 (95% CI, 0.71-1.09).
• In secondary analyses, investigators found results did not differ according to subgroup analyses when stratified by age, sex, or history of prior insulin use or SGLT2 inhibitor molecule.
• There was an increased risk of below-knee amputation among patients meeting the criteria for prevalent new users of SGLT2 inhibitors compared with DPP-4 inhibitor users (HR, 1.29; 95 CI, 0.97-1.70).

Though the findings of the study were reassuring, the authors acknowledged that further studies with a longer duration of follow-up are needed to assess potential long-term effects.

"We found no evidence of an association between SGLT2 inhibitor use and incident below-knee amputation compared with DPP-4 inhibitor use among patients with type 2 diabetes. Similarly, there was no increased risk of below-knee amputation associated with specific SGLT2 inhibitor molecule use compared with DPP-4 inhibitor use," concluded the researchers.

Primary source: Diabetes Care

For the full article, click on the link: https://doi.org/10.2337/dc20-0267