A large Spanish clinical trial has shown that a calorie-restricted Mediterranean diet combined with exercise and counseling reduces the risk of type 2 diabetes by 31 percent in at-risk adults. The PREDIMED-Plus study followed nearly 5,000 participants over six years, demonstrating significant weight loss and waist reduction. Researchers highlight this approach as a practical, scalable strategy to combat the global diabetes epidemic.
The PREDIMED-Plus trial, launched in 2013 by the University of Navarra with initial funding of over €2 million from the European Research Council, expanded to involve more than 200 researchers from 22 institutions across Spain. Total funding exceeded 15 million euros, primarily from the Carlos III Health Institute and CIBER networks. Conducted in over 100 primary care centers within Spain's National Health System, the study enrolled 4,746 adults aged 55 to 75 who were overweight or obese and had metabolic syndrome but no history of cardiovascular disease or diabetes.
From 2014 to 2016, additional institutions joined, and the trial compared two groups over six years. The intervention group followed a calorie-reduced Mediterranean diet—about 600 fewer kilocalories per day—along with moderate physical activity like brisk walking, strength training, and balance exercises, plus professional weight management counseling. The control group adhered to a traditional ad libitum Mediterranean diet without calorie restrictions or exercise guidance.
Results, published in Annals of Internal Medicine in 2025, showed the intervention group reduced their type 2 diabetes risk by 31 percent, preventing about three new cases per 100 participants. They also lost an average of 3.3 kg in weight and 3.6 cm from their waist, compared to 0.6 kg and 0.3 cm in the control group.
"Diabetes is the first solid clinical outcome for which we have shown—using the strongest available evidence—that the Mediterranean diet with calorie reduction, physical activity and weight loss is a highly effective preventive tool," said Miguel Ángel Martínez-González, Professor of Preventive Medicine and Public Health at the University of Navarra and a principal investigator.
Miguel Ruiz-Canela, the study's first author and Chair of Preventive Medicine at the University of Navarra, added, "The Mediterranean diet acts synergistically to improve insulin sensitivity and reduce inflammation. With PREDIMED-Plus, we demonstrate that combining calorie control and physical activity enhances these benefits. It is a tasty, sustainable and culturally accepted approach that offers a practical and effective way to prevent type 2 diabetes—a global disease that is, to a large extent, avoidable."
The trial builds on the earlier PREDIMED study (2003-2010), which showed a 30 percent reduction in cardiovascular disease risk with a Mediterranean diet enriched with olive oil or nuts. Experts, including an editorial in Annals of Internal Medicine by Sharon J. Herring and Gina L. Tripicchio of Temple University, praise the findings for their clinical relevance but note challenges in scaling such interventions beyond Mediterranean contexts, such as access to healthy foods in urban U.S. settings. With type 2 diabetes affecting over 530 million people worldwide, including 4.7 million in Spain and 38.5 million in the U.S., the study underscores lifestyle changes as a cost-effective prevention tool amid rising obesity and urbanization.