Semaglutide · research summary

Tirzepatide versus other anti-diabetic agents for the prevention of diabetic foot complications in patients with type 2 diabetes.

Frontiers in pharmacology · 2026. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

Retrospective cohort study using the TriNetX network
“We conducted a retrospective cohort study using the TriNetX network.”

Subjects

Adults with type 2 diabetes initiating tirzepatide, sulfonylurea, DPP-4 inhibitors, SGLT2 inhibitors, or GLP-1 receptor agonists
“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.”

Sample size

Matched cohorts ranging from 97,457 to 146,321 patients per arm across four comparisons
“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).”

Duration

Follow-up from index date until first outcome, last encounter, death, or 1 year, with median follow-up ranging from 282 to 316 days
“Follow-up began the day after the index date and continued until the first occurrence of any outcome, the last clinical encounter, death, or 1 year after the index date, whichever occurred first.”

Reported findings

Tirzepatide was associated with reduced risk of diabetic foot complications compared to sulfonylureas, DPP-4 inhibitors, and SGLT2 inhibitors
“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 significant difference in diabetic foot complication risk was found between tirzepatide and GLP-1 receptor agonists
“No difference was found versus GLP-1RA (HR, 0.97; 95% CI, 0.91–1.03).”
Tirzepatide showed reduced risk for diabetic foot complications with and without major adverse limb events compared to sulfonylureas, DPP-4 inhibitors, and SGLT2 inhibitors
“TZP was associated with a lower risk of DFC without MALE compared with SU (HR, 0.79; 95% CI, 0.75–0.83), DPP-4i (HR, 0.85; 95% CI, 0.81–0.90), and SGLT2i (HR, 0.90; 95% CI, 0.85–0.95).”

Limitations stated by the authors

Potential residual confounding by indication, lack of diabetes duration data, absence of granular podiatry or footwear data, short follow-up period, and reliance on diagnosis codes which may lead to outcome misclassification
“First, despite rigorous PSM, residual confounding and selection bias cannot be excluded, particularly confounding by indication.”

Source: PubMed 42851503 · DOI 10.3389/fphar.2026.1880132 · all study summaries

Subjects

Adults with type 2 diabetes initiating tirzepatide, sulfonylurea, DPP-4 inhibitors, SGLT2 inhibitors, or GLP-1 receptor agonists

“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.”

Sample size

Matched cohorts ranging from 97,457 to 146,321 patients per arm across four comparisons

“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).”

Duration

Follow-up from index date until first outcome, last encounter, death, or 1 year, with median follow-up ranging from 282 to 316 days

“Follow-up began the day after the index date and continued until the first occurrence of any outcome, the last clinical encounter, death, or 1 year after the index date, whichever occurred first.”

Reported findings

Tirzepatide was associated with reduced risk of diabetic foot complications compared to sulfonylureas, DPP-4 inhibitors, and SGLT2 inhibitors

“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 significant difference in diabetic foot complication risk was found between tirzepatide and GLP-1 receptor agonists

“No difference was found versus GLP-1RA (HR, 0.97; 95% CI, 0.91–1.03).”

Tirzepatide showed reduced risk for diabetic foot complications with and without major adverse limb events compared to sulfonylureas, DPP-4 inhibitors, and SGLT2 inhibitors

“TZP was associated with a lower risk of DFC without MALE compared with SU (HR, 0.79; 95% CI, 0.75–0.83), DPP-4i (HR, 0.85; 95% CI, 0.81–0.90), and SGLT2i (HR, 0.90; 95% CI, 0.85–0.95).”

Limitations stated by the authors

Potential residual confounding by indication, lack of diabetes duration data, absence of granular podiatry or footwear data, short follow-up period, and reliance on diagnosis codes which may lead to outcome misclassification

“First, despite rigorous PSM, residual confounding and selection bias cannot be excluded, particularly confounding by indication.”