Association of Weight Loss and Physical Activity With A1C Reduction in a Diabetes Prevention Program: A Secondary Analysis of a Randomized Clinical Trial

OBJECTIVE Weight loss and physical activity (PA) reduce diabetes risk, but their independent contributions to A1C reduction in prediabetes are not fully quantified. This study examined the associations between weight loss, PA, and the odds of achieving A1C reduction thresholds during a lifestyle intervention. RESEARCH DESIGN AND METHODS This secondary analysis used data from a randomized clinical trial. Participants (n = 209) included adults with prediabetes and overweight/obesity who completed a 12-month follow-up. Weight loss was categorized as none (≤0%), mild (>0–2.5%), moderate (>2.5–5%), and substantial (>5%). PA was objectively measured via actigraphy and grouped into six 75-min weekly increments (ranging from <75 to >375 min). Adjusted logistic regression models estimated odds of achieving A1C reductions (from ≥0.1% to ≥0.4%). RESULTS A dose-dependent relationship was observed between weight loss and A1C reduction. Compared with no weight loss, substantial weight loss (>5%) was associated with increased odds of lowering A1C across all thresholds (≥0.1% to ≥0.4%; odds ratio [OR] range 6.36–9.49, all P ≤ 0.001). Moderate weight loss (>2.5–5%) was associated with increased odds of lowering A1C by ≥0.1% to ≥0.3% (OR range 2.81–4.83, all P < 0.05), although this was not significant for the ≥0.4% threshold. In contrast, PA levels were not significantly associated with A1C reduction compared with the reference group (<75 min/week) in adjusted models across any threshold. CONCLUSIONS These findings support that weight loss may be the primary driver of improved glycemic control in individuals with prediabetes, underscoring the importance of prioritizing weight loss in lifestyle interventions.