SUN-565 - Does Metformin Protect Youth with Prediabetes from Developing Type 2 Diabetes?

Background
Prediabetes affects nearly 18% of U.S. youth and is a major precursor to Type 2 Diabetes (T2DM). Youth, particularly non-Hispanic Black children, experience faster progression than adults due to rapid β-cell decline. Lifestyle modification is the first-line therapy, and since metformin is helpful in adults with prediabetes, it is sometimes used in youth despite its efficacy remaining uncertain.

Objective:
To determine whether treatment with metformin is associated with reduced risk of progression to T2DM compared with lifestyle modification alone in youth with prediabetes in real world clinical practice.

Design/Method
We conducted a retrospective chart review of youth with prediabetes and body mass index (BMI) ≥85th percentile seen between 2019 and 2024. Prediabetes was defined as A1c 5.7–6.4%. Patients were categorized into metformin with lifestyle modification (MET) or lifestyle modification alone (LM) groups. The primary outcome was progression to T2DM, defined by ADA criteria (A1c ≥6.5%, or ICD-9/10 diagnosis of T2DM).

Results
We reviewed 1431 youth with prediabetes who were observed for a mean of 3 years (range 0.11–5). Of these, 666 (46.5%) were female and 1014 (70.8%) were of African American/Caribbean descent. At baseline, compared with the LM group (n=1279), the MET group (n=152) had higher proportion of females (69.3% vs 44.2%, p< 0.001), higher BMI (35.21±7.65 vs 29.47±7.37 kg/m², p< 0.001), and higher baseline A1c (5.91±0.20% vs 5.80±0.13%, p< 0.001).
Overall, 78/1431(5.45%) progressed to T2DM with higher incidence in MET group compared with LM (19.7% vs 3.8%, χ²p < 0.001). Among those who progressed, time to diagnosis was longer in the MET group compared with LM (median 2.8 vs 1.6 years, p=0.003). In multivariable logistic regression adjusting for age, sex, BMI, and A1c, MET use remained associated with higher odds of progression (OR 2.68, 95% CI 1.53–4.69, p=0.0005). Higher baseline A1c and BMI were also independent predictors of progression.
Within MET, patients who progressed had higher baseline A1c (p = 0.025) and nonsignificant trend toward higher BMI. Within LM, both baseline A1c (p < 0.001) and BMI (p < 0.001) were strong predictors of progression.

Conclusions
Counterintuitively, MET use was associated with higher rates of progression to T2DM compared with LM but a longer time to progression, likely reflecting confounding by indication, as higher-risk youth were more frequently prescribed MET. Baseline A1c and BMI were key predictors of progression. Clinicians can identify these patients, but MET alone may be insufficient to prevent diabetes progression in high-risk youth. More females received MET, possibly due to polycystic ovary syndrome. More intensive interventions such as GLP-1 receptor agonists may be needed to prevent diabetes progression in high-risk youth, although access remains limited. Medication adherence could not be confirmed in this study.

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