A Mediterranean diet is already famous for its heart and metabolic benefits. But a major Spanish clinical trial suggests it may work even better against type 2 diabetes when paired with three realistic upgrades: eating fewer calories, moving more, and getting professional support for weight loss.

The PREDIMED-Plus trial found that this more structured version of Mediterranean living reduced the risk of developing type 2 diabetes by 31%. The project is the largest nutrition trial conducted in Europe and involved the University of Navarra along with more than 200 researchers from 22 other Spanish universities, hospitals, and research centers. The work was carried out in more than 100 primary care centers within Spain’s National Health System.

A Smarter Version of a Famous Diet

PREDIMED-Plus began in 2013 after the University of Navarra received an Advanced Grant from the European Research Council (ERC) worth more than €2 million. Between 2014 and 2016, additional institutions joined, bringing total funding to more than 15 million euros. Most of that support came from the Carlos III Health Institute (ISCIII) and the Center for Biomedical Research Network through its areas of Physiopathology of Obesity and Nutrition (CIBEROBN), Epidemiology and Public Health (CIBERESP) and Diabetes and Associated Metabolic Diseases (CIBERDEM ).

The results, published in Annals of Internal Medicine, were based on 4,746 adults between ages 55 and 75. All had overweight or obesity and metabolic syndrome, but none had diabetes or cardiovascular disease at the start of the study. Researchers followed participants for six years to see whether a more intensive Mediterranean based lifestyle plan could offer stronger protection against type 2 diabetes than the traditional Mediterranean diet alone.

One group followed a calorie reduced Mediterranean diet (about 600 kcal fewer per day), added moderate physical activity (brisk walking, strength and balance training), and received professional guidance. The comparison group followed a traditional Mediterranean diet without calorie restriction or exercise advice.

Small Changes, Big Diabetes Protection

The difference between the two approaches was striking. Participants in the intervention group were 31% less likely to develop type 2 diabetes than those in the comparison group.

They also lost more weight and reduced abdominal fat more effectively. On average, the intervention group lost 3.3 kg and reduced waist circumference by 3.6 cm. The control group lost only 0.6 kg and trimmed waist size by 0.3 cm.

In real world terms, the researchers estimated that the program prevented about three cases of type 2 diabetes for every 100 participants. For a condition affecting hundreds of millions of people globally, that kind of prevention could add up quickly if applied broadly among people at elevated risk.

“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, Adjunct Professor of Nutrition at Harvard University, and one of the principal investigators of the project. “Applied at scale in at-risk populations, these modest and sustained lifestyle changes could prevent thousands of new diagnoses every year. We hope soon to show similar evidence for other major public health challenges.”

Why This Matters for a Global Health Crisis

Type 2 diabetes is one of the world’s fastest growing chronic diseases. The International Diabetes Federation estimates that more than 530 million people worldwide now live with diabetes. The rise has been fueled by urbanization, less healthy diets, more sedentary lifestyles, reduced physical activity, population aging, and increasing rates of overweight and obesity.

Spain has about 4.7 million adults with diabetes (most of them type 2), one of the highest rates in Europe. Across Europe, more than 65 million people have diabetes. In the United States, about 38.5 million people are affected, and the country has one of the highest health care costs per patient in the world. Experts warn that prevention is essential because type 2 diabetes raises the risk of cardiovascular, kidney, and metabolic complications.

“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,” explained Miguel Ruiz-Canela, Professor and Chair of Preventive Medicine and Public Health Department at the University of Navarra’s School of Medicine and first author of the study. “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.”

Newer Research Adds More Context

Since the PREDIMED-Plus diabetes findings were prepared, related research has continued to strengthen the broader picture. A PREDIMED-Plus body composition analysis published in JAMA Network Open found that the energy reduced Mediterranean diet plus physical activity helped reduce total and visceral fat while slowing age related loss of lean mass in older adults with overweight or obesity and metabolic syndrome. That matters because visceral fat and declining muscle are closely tied to cardiometabolic risk.

More recent PREDIMED-Plus work has also explored how sedentary time may affect cardiovascular health. A 2026 study in BMC Cardiovascular Disorders reported that replacing sedentary time with physical activity was associated with favorable five year changes in high sensitivity troponin T, a blood marker related to heart stress, although the pattern was not consistent across all atrial fibrillation related biomarkers.

Other recent Mediterranean diet research continues to support the pattern’s broader cardiovascular value. A 2025 review in Cardiovascular Research described the Mediterranean diet as one of the best studied dietary patterns for cardiovascular prevention, citing large randomized trials including PREDIMED, PREDIMED-Plus, CORDIOPREV, and the Lyon Diet Heart Study.

A 2026 analysis from the original PREDIMED trial also highlighted the possible importance of food quality within the diet. Participants with higher cumulative intake of extra virgin olive oil had a lower risk of a broad cardiovascular outcome, while common olive oil showed weaker associations. The finding supports a practical message for readers: the Mediterranean diet is not only about eating less or eating more plants. The type and quality of fats may matter too.

A Practical Strategy, Not a Fad

Annals of Internal Medicine published the study alongside an editorial by Sharon J. Herring and Gina L. Tripicchio, nutrition and public health experts at Temple University (Philadelphia, USA). They praised the clinical importance of the intervention and its potential as a model for preventing type 2 diabetes.

At the same time, they cautioned that bringing the same strategy to places outside the Mediterranean region, including the U.S., would require more than individual willpower. Barriers such as unequal access to healthy food, urban environments that make physical activity harder, and limited access to professional guidance could all stand in the way. They argued that public policies should help create healthier and more equitable environments.

That point is especially relevant now, as drugs for obesity and diabetes continue to attract major attention. PREDIMED-Plus shows that medication is not the only path with power. Sustained lifestyle changes, when supported properly, can still produce major health gains.

Built on Decades of Mediterranean Diet Research

The PREDIMED-Plus project (2013-2024), which involves different patients, builds on the earlier PREDIMED study (2003-2010). That previous trial showed that a Mediterranean diet enriched with extra virgin olive oil or nuts reduced cardiovascular disease risk by 30%.

Researchers say the updated PREDIMED-Plus strategy could be used by primary care providers as a sustainable and cost efficient way to help prevent type 2 diabetes on a broad scale. The intervention does not rely on extreme dieting. It combines familiar foods, moderate activity, gradual weight loss, and professional support.

A Nationwide Research Effort

The PREDIMED-Plus trial brought together a large network of investigators from across Spain. In order of participant numbers, participating institutions included the University of Navarra and the Navarra Health Service (2 centers), Hospital Clínic de Barcelona (2 centers), University of Valencia, Rovira i Virgili University (Reus), IMIM-Hospital del Mar, Miguel Hernández University (Alicante), Son Espases Hospital (Palma de Mallorca), University of Malaga, Reina Sofía Hospital (Córdoba) and University of Granada.

Other participants included Bioaraba and the UPV/EHU (Vitoria), the University of the Balearic Islands, the Hospital Virgen de la Victoria (Malaga), the University of Las Palmas de Gran Canaria, the University of Leon, the Primary Health Care District of Seville, the Fundación Jiménez Díaz (Madrid), the Hospital de Bellvitge, the Hospital Clínico San Carlos (Madrid), the University of Jaen, and the IMDEA Food Institute (Madrid).

The project also included international collaboration with the Harvard T.H. Chan School of Public Health. Most participating researchers are affiliated with CIBEROBN, CIBERESP, or CIBERDEM.



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