Continuous high insulin levels are associated with weight gain and lead to cardiometabolic diseases. Therefore, we have developed the Low-Insulin-Method and integrated it into the multi-component, occupational healthcare program SHAPE-AND-MOTION-Medical-Accompanied-Slimming (SAMMAS) to reduce daily insulin levels for long-term weight reduction in overweight or obesity. Employees were randomized into a starting intervention group (SI, = 15) or waiting list control group (WL, = 15). SAMMAS consisted of group-based seminars, low-carbohydrate nutrition including formula diet, continuous glucose monitoring, telemetric monitoring, and telemedical coaching. Both groups received telemetric devices at baseline. Intention-to-treat analyses were performed after 12, 26, and 52 weeks. The estimated treatment difference in weight reduction after 12 weeks, which is the primary endpoint of the study, showed a pronounced effect in favour of SI (-6.3 kg with (95% confidence interval) (-7.4; -4.5) ( < 0.001)) after 12 weeks. Furthermore, SI improved fasting blood glucose, HbA1c, quality of life, fasting insulin, blood pressure, and eating behaviour (all < 0.05) in the within-group analysis, while WL did not. After 26 and 52 weeks, weight reduction could be maintained in the whole group (both groups together) by -6.7 kg (-9.5; -3.8) ( < 0.001) and -6.1 kg (-9.2; -2.7) ( < 0.01). SAMMAS supports clinically relevant weight reduction and long-term weight loss maintenance in individuals with overweight or obesity.