Identification of participants’ characteristics who benefited most from large community-based intervention studies may guide future prevention initiatives in order to maximize their effectiveness. The current study aimed to examine the socio-demographic, anthropometric, and behavioral characteristics, as well as the health and eating perceptions of those who improved their lipidemic profile, in the Feel4Diabetes early screening and prevention program. In the present analyses, 1773 adults from families at high risk for developing type 2 diabetes mellitus (T2DM) were enrolled, receiving either the standard care or the more intensive intervention, and 33.3–55.2% of them improved one or more of their lipidemic indices by >5%. Women, people living in Southeastern Europe, coming from two-parent families, having higher financial security, educational level and better diet quality were associated with a 27–64% higher likelihood for benefiting from the program regarding one or more of their lipidemic profile indices. Participants who were overweight or obese (especially with central obesity), employed, with prolonged sedentary behavior, prone to emotional eating and perceiving their weight status as lower than their actual weight were 24–43% less likely to have benefited. These findings should guide future interventions, prioritizing regions in greater need, and being tailor-made to specific population characteristics in order to further improve their effectiveness.