Nearly 98 million American adults have prediabetes, according to the CDC’s most recent national data, and most of them have been told the same thing: lose weight. A large clinical trial out of Spain now suggests that advice is incomplete. Older adults who followed a calorie-trimmed Mediterranean diet and added regular exercise cut their risk of developing type 2 diabetes by roughly one-third, and the protection held even among those who barely moved the needle on the scale.
The results, from the PREDIMED-Plus trial, were published in JAMA Internal Medicine and summarized by the Harvard T.H. Chan School of Public Health. They challenge a long-standing clinical assumption: that lifestyle interventions prevent diabetes primarily by producing weight loss. In this trial, what people ate and how much they moved mattered on their own.
Inside the PREDIMED-Plus trial
PREDIMED-Plus (NCT01087086 on ClinicalTrials.gov) is a randomized trial that enrolled more than 6,800 adults ages 55 to 75 across 23 research centers in Spain. Every participant carried excess weight and at least three features of metabolic syndrome, a cluster of conditions including high blood sugar, elevated blood pressure, and abdominal obesity that sharply raises cardiovascular and diabetes risk.
Researchers randomly assigned participants to one of two groups. The intensive arm received personalized coaching to cut about 300 calories per day from their usual intake, follow a Mediterranean eating pattern rich in extra-virgin olive oil, vegetables, legumes, fish, and whole grains, and build up to at least 45 minutes of brisk walking or equivalent activity six days a week. The control arm got general advice to follow a Mediterranean diet but no calorie targets and no structured exercise plan.
Both groups, in other words, ate well. The question was whether layering calorie reduction and exercise on top of an already healthful diet would deliver additional metabolic protection.
The results: protection beyond the scale
Over a median follow-up of about 4.3 years, participants in the intensive group developed type 2 diabetes at a rate roughly 33 percent lower than those in the control group. That is a striking margin, especially considering that the control diet was itself a Mediterranean pattern, not a typical Western diet.
The more surprising finding involved weight. Many participants in the intensive arm lost only modest amounts, yet they still showed significantly lower diabetes incidence. According to the Harvard Chan School summary, the benefit “was not fully explained by weight loss,” pointing instead to improvements in insulin sensitivity and reductions in chronic low-grade inflammation as likely contributors.
That distinction matters for the millions of people who struggle to lose large amounts of weight and assume, as a result, that lifestyle changes aren’t “working.” PREDIMED-Plus suggests the metabolic payoff from better food choices and consistent movement begins well before the scale reflects it.
How this compares to earlier landmark research
The findings echo and extend results from the U.S. Diabetes Prevention Program (DPP), which showed in 2002 that intensive lifestyle intervention reduced diabetes risk by 58 percent in adults with prediabetes. The DPP, however, set a 7 percent body-weight-loss target and used a general low-fat, low-calorie diet rather than a Mediterranean pattern. PREDIMED-Plus adds a new dimension: it shows that a specific, well-studied dietary pattern, combined with moderate calorie reduction and exercise, delivers strong protection even when weight loss falls short of traditional targets.
The comparison also matters pharmacologically. The DPP found that metformin reduced diabetes risk by 31 percent, a figure strikingly close to the PREDIMED-Plus lifestyle result. For clinicians counseling patients with prediabetes, the Spanish trial reinforces that a well-structured lifestyle program can rival medication, consistent with American Diabetes Association guidelines that recommend lifestyle intervention as the first-line approach.
What the Mediterranean diet looked like in practice
Participants in the intensive arm weren’t handed a rigid meal plan. Instead, dietitians coached them to build meals around a few core principles:
- Fats: Extra-virgin olive oil as the primary cooking and dressing fat, plus nuts in moderate portions.
- Protein: Fish and legumes several times a week, with poultry preferred over red meat and processed meats sharply limited.
- Carbohydrates: Whole grains, fruits, and vegetables as staples; refined grains, pastries, and sugary drinks discouraged.
- Portions: A target reduction of roughly 300 calories per day from each person’s baseline, achieved through smaller servings and fewer energy-dense snacks rather than skipping meals.
The exercise prescription was similarly grounded. Walking was the backbone, with a goal of 45 minutes of moderate activity on most days. Participants received pedometers and periodic check-ins to keep them on track. The program was designed to be sustainable over years, not weeks.
Important caveats
No single trial settles a question this large, and several limitations deserve attention.
Population: PREDIMED-Plus enrolled older Spanish adults with metabolic syndrome. Spain’s food environment, cultural eating habits, and healthcare infrastructure differ from those in the United States. Whether the same magnitude of benefit would appear in younger, more ethnically diverse populations or in food environments dominated by ultra-processed options has not been tested.
Adherence: The published summary does not break down how closely participants stuck to calorie and exercise targets over the full follow-up period, or whether the most adherent participants drove the bulk of the benefit. Future sub-analyses from the PREDIMED-Plus consortium should clarify this.
Mechanisms: While improved insulin sensitivity and reduced inflammation are plausible explanations for the weight-independent benefit, detailed biomarker trajectories (fasting insulin, C-reactive protein, HbA1c trends) are not fully laid out in the summary sources. The consortium has published related biomarker sub-studies, but a complete mechanistic picture is still forming.
Control group quality: Because the control arm also followed a Mediterranean diet, the absolute diabetes rates in both groups may have been lower than what would be seen in a population eating a standard Western diet. The relative risk reduction of one-third is measured against an already-healthful baseline, which arguably makes the finding more impressive but also means the intervention’s edge over a typical American diet could be even larger.
What this means for people with prediabetes right now
For the roughly one in three U.S. adults living with prediabetes, PREDIMED-Plus reinforces a message that is easy to state but hard to internalize: the goal is not a number on the scale. It is a pattern of living. Shifting toward a Mediterranean-style diet, trimming a few hundred calories a day without crash dieting, and walking briskly most days of the week produced meaningful, measurable protection against type 2 diabetes in a rigorous trial, even when participants’ weight barely changed.
That reframing could matter most for people who have tried and failed to hit aggressive weight-loss targets and concluded that lifestyle changes don’t work for them. The evidence from this trial, consistent with the broader arc of metabolic research published through early 2025, says otherwise: the changes are working, even if the scale hasn’t caught up yet.
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*This article was researched with the help of AI, with human editors creating the final content.
