A low-calorie Mediterranean diet combined with physical activity reduces the risk of developing diabetes

The first results provide solid evidence, for the first time, that this combined strategy is effective in reducing the risk of developing type 2 diabetes. PREDIMED-Plus is a Spanish multicentre clinical trial funded with more than €15 million through different calls, but mainly supported by the ISCIII and the CIBER consortium. It followed thousands of participants throughout Spain for six years. CIBER, which reports to the Spanish Ministry of Science, Innovation and Universities, brings together Spain’s leading research groups in various fields with the aim of promoting high-quality research in biomedicine and health.

Type 2 diabetes, a chronic disease that seriously impairs health and quality of life, has increased significantly in recent years in parallel with the obesity epidemic. For this reason, this work has sought to promote accessible and sustainable strategies focused on prevention.

The earlier PREDIMED study (PREvención con DIeta MEDiterránea), active for more than two decades, had already shown that a Mediterranean diet supplemented with extra virgin olive oil or nuts reduced the incidence of diabetes by 30% compared with a low-fat diet. However, this reduction was observed with only a barely noticeable decrease in body weight.

Building on that knowledge, the PREDIMED-Plus study proposed a more intensive lifestyle intervention, with the aim of assessing whether it could deliver additional benefits compared with other less intensive strategies. This approach is based on weight loss through a slightly hypocaloric Mediterranean diet — rich in fibre and with a low glycaemic index — combined with the promotion of physical activity and behavioural support.

The study now published included 4,746 participants aged 55 to 75 who were overweight or obese, had metabolic syndrome and did not have cardiovascular disease or diabetes at baseline. Participants were randomly assigned (50% probability) to one of two programmes: one focused on following the Mediterranean diet (without promoting physical activity or targeting calorie restriction), and another behavioural programme aimed at achieving weight loss through a calorie-reduced Mediterranean diet (with a planned reduction of 600 kilocalories per day) together with increased physical activity.

After six years of follow-up, it was observed that participants without diabetes at baseline who were assigned to the intensive intervention group (Mediterranean diet plus physical activity) showed greater adherence to the Mediterranean diet, increased their physical activity, lost more weight and required fewer glucose-lowering medications after being diagnosed with diabetes.

Furthermore, the absolute risk of developing diabetes was 12% (349 cases) among participants who followed only the Mediterranean diet, compared with 9.5% (280 cases) among those assigned to the intensive intervention. This latter strategy reduced new cases of diabetes by 31% compared with the Mediterranean diet without calorie restriction or exercise recommendations.

The research team concludes that the foods and nutrients that make up the Mediterranean diet “act synergistically through different mechanisms involved in type 2 diabetes, such as reducing insulin resistance, inflammation and oxidative stress. These effects are enhanced by physical activity and weight loss. Moreover, since it is a tasty, sustainable and culturally acceptable diet, it can become an ideal long-term strategy for the prevention of cardiometabolic diseases”.

Reference:
Miguel Ruiz-Canela, Dolores Corella, Miguel Ángel Martínez-González, et al. Comparison of an Energy-Reduced Mediterranean Diet and Physical Activity Versus an Ad Libitum Mediterranean Diet in the Prevention of Type 2 Diabetes:A Secondary Analysis of a Randomized Controlled Trial. Ann Intern Med. [Epub 26 August 2025]. doi: 10.7326/ANNALS-25-00388