Association Between Serum Vitamin D Levels and Metformin Efficacy in Obese Type 2 Diabetes Patients: A Retrospective...

To investigate the association between baseline serum 25-hydroxyvitamin D [25(OH)D] levels and glycemic response to metformin monotherapy in obese adults with type 2 diabetes mellitus (T2DM).

This single-center retrospective cohort study analyzed the electronic medical records (January 2021-December 2023) of obese T2DM patients initiating metformin monotherapy. Participants were stratified by baseline 25(OH)D levels: deficiency (<20 ng/mL, n = 256) or sufficiency (≥20 ng/mL, n = 171). Propensity score matching (1:1) balanced covariates (age, sex, BMI, HbA1c, diabetes duration, comorbidities, season), yielding 142 matched pairs (n = 284). The primary outcome was absolute HbA1c reduction (ΔHbA1c) at 3 months. Multivariable linear regression, subgroup, and sensitivity analyses were performed.

In the matched cohort, vitamin D-sufficient patients achieved a clinically meaningful and statistically significant greater HbA1c reduction versus vitamin D-deficient patients (mean difference: 0.34%; 95% CI: 0.16-0.52%; p < 0.001). Baseline 25(OH)D positively correlated with ΔHbA1c (r = 0.32, p < 0.001). Multivariable regression confirmed that vitamin D sufficiency independently predicted greater ΔHbA1c (adjusted β = 0.41%, 95% CI: 0.22-0.60%, p < 0.001). Subgroup analyses revealed enhanced effects in females (p-interaction = 0.018), patients >60 years (β = 0.49% vs ≤60 years 0.33%, p-interaction = 0.009), and baseline HbA1c ≥8.5% (β = 0.56% vs <8.5% 0.21%, p-interaction = 0.003). Adverse events were comparable between groups.

Higher baseline vitamin D levels (≥20 ng/mL) are associated with significantly improved metformin efficacy in obese T2DM patients, particularly among females, older adults, and those with poorer glycemic control. Vitamin D status may serve as a predictive biomarker for metformin response.