Association Between Serum Vitamin D Levels and Metformin Efficacy in Obese Type 2 Diabetes Patients: A Retrospective Cohort Study Based on HbA1c Reduction

Yimeng Wang, Hongli Liu, Yijia Li, Xiaoxue Wang, Chen He, Zhi Wei Endocrinology Department, Hanzhong Central Hospital, Hanzhong, People’s Republic of ChinaCorrespondence: Zhi Wei, Endocrinology Department, Hanzhong Central Hospital, No. 557, Middle West Labor Road, Hantai District, Hanzhong City, Shaanxi Province, 723000, People’s Republic of China, Email [email protected]: 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).Patients and Methods: 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.Results: 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.Conclusion: 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.Plain Language Summary: Why was this Study Done?Many people with type 2 diabetes also have low vitamin D levels, especially if they are living with obesity. Vitamin D helps the body use insulin properly. Metformin is a common diabetes medicine, but it does not work the same for everyone. We wanted to determine whether having enough vitamin D helps metformin work better.What did the Researchers do?We looked back at health records of 427 obese adults with type 2 diabetes who started taking metformin alone. We split them into two groups: those with low vitamin D (less than 20 ng/mL) and those with enough vitamin D (20 ng/mL or more). We compared how much their blood sugar levels (HbA1c) improved after three months.What did the Researchers Find?People with enough vitamin D had a significantly greater improvement in blood sugar levels than those with low vitamin D. This effect was especially strong in women, people over 60, and those with higher starting blood sugar levels. Vitamin D levels were positively correlated with a better response to metformin. Side effects were similar in both groups.What do these Results Mean?Having enough vitamin D may help metformin work better in people with type 2 diabetes and obesity. Checking vitamin D levels when starting metformin could help doctors predict how well the treatment will work. Future studies should test whether giving vitamin D supplements can actually improve diabetes control in those who are deficient.Keywords: vitamin D, metformin, HbA1c, obesity, type 2 diabetes, biomarker