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Ethnic differences in the comparative effectiveness of second-line type 2 diabetes medications in preventing

Mia Harley1, Christopher T Rentsch1,2, Elizabeth Williamson1

  • 1Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.

Diabetes, Obesity & Metabolism
|November 12, 2025
PubMed
Abstract

Insights

This study found dipeptidyl peptidase-4 inhibitors (DPP4i) may be more effective than sulfonylureas (SU) for cardiovascular outcomes in Black individuals with type 2 diabetes. No other ethnic differences in treatment effects were observed.

Area of Science:

  • Cardiology
  • Endocrinology
  • Pharmacology

Background:

  • Type 2 diabetes management involves various drug classes with differing cardiovascular profiles.
  • Ethnic variations in drug response necessitate investigation into comparative effectiveness.

Purpose of the Study:

  • To compare the effectiveness of sulfonylureas (SU), dipeptidyl peptidase-4 inhibitors (DPP4i), and sodium-glucose cotransporter-2 inhibitors (SGLT2i) on cardiovascular outcomes across different ethnicities.
  • To identify potential ethnic disparities in the efficacy of these diabetes medications.

Main Methods:

  • Retrospective analysis of UK electronic health records (2015-2022) for adults with type 2 diabetes.
  • Inclusion of patients initiating SU, DPP4i, or SGLT2i.
  • Major adverse cardiovascular events (MACE) defined as myocardial infarction, stroke, heart failure hospitalization, or cardiovascular death.
  • Cox proportional hazards models used to estimate hazard ratios, with Wald tests for ethnic interaction.

Main Results:

  • Analysis included 91,116 individuals: 72.3% White, 14.2% South Asian, 6.0% Black.
  • Weak evidence of ethnic interaction for DPP4i vs. SU on MACE (p=0.12), with stronger effects for DPP4i in Black individuals (HR 0.64).
  • Evidence of ethnic interaction for DPP4i vs. SU on heart failure hospitalization (p=0.05), with a stronger effect in Black individuals (HR 0.50).
  • No significant ethnic differences observed for other treatment comparisons or cardiovascular outcomes.

Conclusions:

  • DPP4i demonstrated a potentially greater effect than SUs in reducing MACE among Black individuals, particularly for heart failure hospitalization.
  • The study found limited evidence for other ethnic differences in the comparative effectiveness of SUs, DPP4i, and SGLT2i on cardiovascular outcomes.
  • Further research is warranted to confirm these ethnic-specific findings in diabetes pharmacotherapy.
Keywords:
DPP‐4 inhibitorSGLT2 inhibitorcardiovascular diseasereal‐world evidencesulphonylureastype 2 diabetes

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