Frontiers in pharmacology · 2026
Tirzepatide versus other anti-diabetic agents for the prevention of diabetic foot complications in patients with type 2 diabetes.
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Kuo Chia-Yu, Wu Jheng-Yan, Tsai Ya-Wen, Lai Chih-Cheng, Wang Jiun-Ling
Аннотация
BACKGROUND: Diabetic foot complications affect up to 25% of patients with type 2 diabetes (T2D) and represent a major cause of morbidity. The dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist - tirzepatide (TZP) has demonstrated superior glycemic control compared with semaglutide however, evidence regarding its effects on diabetic foot complications (DFCs) remains limited.
METHODS: We conducted a retrospective cohort study using the TriNetX network. Adults with T2D initiating TZP, sulfonylurea (SU), dipeptidyl peptidase-4 inhibitors (DPP-4is), sodium-glucose cotransporter-2 inhibitors (SGLT2is), and glucagon-like peptide-1 receptor agonists (GLP-1RAs) between January 2022 and July 2025 were included. Propensity score matching created balanced cohorts for four comparisons. The primary outcome was the risk of DFC - a composite of ulcers, infections, critical limb ischemia, and revascularization or amputation.
RESULTS: After matching, four cohorts included 141,002 patients per arm (TZP vs. SU), 131,449 patients per arm (TZP vs. DPP-4i), 146,321 patients per arm (TZP vs. SGLT2i), and 97,457 patients per arm (TZP vs. GLP-1RA). Compared with SU, TZP was associated with reduced diabetic foot complications (HR, 0.80; 95% CI, 0.76-0.84). Similar reductions were observed versus DPP-4i (HR, 0.83; 95% CI, 0.78-0.87) and SGLT2i (HR, 0.88; 95% CI, 0.83-0.92). No difference was found versus GLP-1RA (HR, 0.97; 95% CI, 0.91-1.03).
CONCLUSION: TZP was associated with a reduction in diabetic foot complications compared with SU, DPP-4i, and SGLT2i, with outcomes similar to GLP-1RA. These findings suggest tirzepatide may be a valuable option for patients at risk of ulceration or amputation.
METHODS: We conducted a retrospective cohort study using the TriNetX network. Adults with T2D initiating TZP, sulfonylurea (SU), dipeptidyl peptidase-4 inhibitors (DPP-4is), sodium-glucose cotransporter-2 inhibitors (SGLT2is), and glucagon-like peptide-1 receptor agonists (GLP-1RAs) between January 2022 and July 2025 were included. Propensity score matching created balanced cohorts for four comparisons. The primary outcome was the risk of DFC - a composite of ulcers, infections, critical limb ischemia, and revascularization or amputation.
RESULTS: After matching, four cohorts included 141,002 patients per arm (TZP vs. SU), 131,449 patients per arm (TZP vs. DPP-4i), 146,321 patients per arm (TZP vs. SGLT2i), and 97,457 patients per arm (TZP vs. GLP-1RA). Compared with SU, TZP was associated with reduced diabetic foot complications (HR, 0.80; 95% CI, 0.76-0.84). Similar reductions were observed versus DPP-4i (HR, 0.83; 95% CI, 0.78-0.87) and SGLT2i (HR, 0.88; 95% CI, 0.83-0.92). No difference was found versus GLP-1RA (HR, 0.97; 95% CI, 0.91-1.03).
CONCLUSION: TZP was associated with a reduction in diabetic foot complications compared with SU, DPP-4i, and SGLT2i, with outcomes similar to GLP-1RA. These findings suggest tirzepatide may be a valuable option for patients at risk of ulceration or amputation.