Lifestyle changes aimed at improving diet, physical activity and weight appear to have benefits that may last well beyond diabetes prevention.
A long-running US clinical trial has found that adults with prediabetes who were assigned to an intensive lifestyle programme had a lower long-term risk of developing multiple chronic health conditions than those assigned to placebo. The benefit was seen over more than two decades of follow-up.
The findings, published in JAMA, suggest that structured lifestyle support may help reduce the wider burden of chronic disease in people at high risk of type 2 diabetes. Metformin, a commonly used diabetes medicine, did not significantly reduce the risk of multiple chronic conditions in this analysis.
Why multimorbidity matters
Prediabetes means blood sugar levels are higher than normal but not high enough for a diagnosis of type 2 diabetes. It is common, particularly in midlife and older age, and is linked with a higher risk of future diabetes, heart disease and other health problems.
The new study focused on multimorbidity, which means having two or more long-term health conditions at the same time. This is increasingly common as populations age. It can make daily life harder, increase the need for medicines and medical appointments, and raise the risk of disability and hospital admission.
Many public health efforts focus on preventing one disease at a time. But in real life, chronic conditions often cluster together.
Diabetes, high blood pressure, kidney disease, heart disease, arthritis and depression can overlap, and one condition may increase the risk or severity of another.
What was already known
Previous research from the Diabetes Prevention Program, a major US trial funded by the National Institutes of Health, showed that intensive lifestyle intervention and metformin could reduce or delay the development of type 2 diabetes in adults at high risk.
The lifestyle programme focused on weight loss through reduced calorie and fat intake, along with regular physical activity. Participants were encouraged to achieve at least 150 minutes of physical activity a week and to lose at least 7% of their starting body weight.
Metformin has also been shown to help prevent or delay type 2 diabetes in some people with prediabetes, especially those at higher risk.
What has been less clear is whether these approaches reduce the risk of developing several chronic conditions over time, not just diabetes.
What the new study found
The new analysis used data from a human clinical trial conducted at 27 sites in the United States. It included 1,173 adults with prediabetes who were at high risk of diabetes, were enrolled in Medicare, and had agreed to link their health data with Centers for Medicare & Medicaid Services claims.
Participants were originally randomly assigned between 1996 and 1999 to one of three groups, intensive lifestyle intervention, metformin, and placebo.
They were then followed through the Diabetes Prevention Program Outcomes Study until 2021.
By the end of follow-up, multimorbidity was very common. Overall, 85% of participants had developed two or more chronic conditions.
Compared with the placebo group, people assigned to the lifestyle intervention had a 21% lower risk of developing two chronic conditions and a 25% lower risk of developing three chronic conditions.
People assigned to metformin did not have a statistically significant reduction in multimorbidity risk.
In plain terms, the study suggests that adults with prediabetes who received structured lifestyle support were less likely, over time, to accumulate multiple long-term health conditions.
Which conditions were included
The researchers examined 15 chronic conditions commonly recorded in Medicare data. These included hypertension, heart disease, stroke, arthritis, chronic kidney disease, chronic obstructive pulmonary disease, cancer, depression, dementia, osteoporosis and diabetes.
Importantly, the results persisted even when diabetes was removed from the definition of multimorbidity. That suggests the lifestyle intervention may have had benefits beyond simply delaying diabetes.
How lifestyle changes may reduce wider health risk
The study was not designed to prove exactly why lifestyle intervention reduced multimorbidity risk, but several pathways are biologically plausible.
First, weight loss can improve the body’s response to insulin. Insulin is the hormone that helps move sugar from the blood into cells. When insulin works better, blood sugar levels tend to improve, reducing strain on blood vessels, kidneys and the heart.
Second, regular physical activity can lower blood pressure, improve cholesterol patterns and support healthier blood vessel function. These changes may reduce the risk of cardiovascular disease over time.
Third, a healthier diet and increased activity can reduce excess body fat, particularly around the abdomen. Abdominal fat is linked with low-grade inflammation and metabolic changes that are associated with several chronic diseases.
Fourth, better fitness and mobility may help protect against frailty, falls and loss of independence, although this specific study did not focus primarily on those outcomes.
These mechanisms are not separate. They can reinforce each other. For example, physical activity may support weight control, improve mood, reduce blood pressure and help preserve muscle strength at the same time.
How strong is the evidence?
This is stronger evidence than a simple observational study because the original Diabetes Prevention Program was a randomised clinical trial. Random assignment helps reduce bias, because participants are allocated to groups by chance rather than by personal choice.
The long follow-up is also a major strength. Chronic diseases develop over years, so studies that track people for two decades can provide information that shorter trials cannot.
However, there are important limitations.
The analysis included participants who were enrolled in Medicare and agreed to claims linkage. This may limit how well the findings apply to younger adults, people outside the US health system or people with different social and medical backgrounds.
The study relied on Medicare claims to identify chronic conditions. Claims data are useful for large studies, but they are collected for billing and administration, not primarily for research. Some diagnoses may be missed or recorded inconsistently.
The trial also changed over time. After the initial Diabetes Prevention Program ended, all participants were offered the intensive lifestyle curriculum in group sessions. During the follow-up study, all groups received some ongoing lifestyle support, while the original lifestyle group received additional booster sessions. This may have reduced differences between groups.
Metformin use may also have varied after the trial period, and long-term adherence to lifestyle changes is difficult to measure precisely.
Even with these caveats and research limitations, the findings support the view that structured lifestyle intervention can have broad and lasting health effects in adults at high risk of diabetes.
What this means for patients and the public
For people with prediabetes, the findings reinforce current medical advice, lifestyle changes remain a central part of reducing future health risk.
This does not mean that every person with prediabetes can prevent chronic disease through lifestyle alone. Age, genetics, income, work, housing, access to healthy food, disability and existing health conditions all affect what is realistic and effective.
But the study suggests that structured support, not just brief advice, may matter. The original programme involved individual sessions, clear goals, ongoing follow-up and help with behaviour change.
People who have been told they have prediabetes should not stop or start medicines based on this study alone. Anyone taking metformin or other medication should discuss treatment decisions with their doctor, pharmacist or diabetes care team.
Where this fits with prevention and treatment
Metformin remains an important medicine for type 2 diabetes and may be used in some people at high risk of developing diabetes. This study does not show that metformin is ineffective for diabetes prevention. Rather, it found no statistically significant reduction in the broader outcome of multimorbidity in this group over long-term follow-up.
The results may be relevant for health policy because multimorbidity is costly for both patients and health systems. If structured lifestyle programmes reduce the accumulation of chronic conditions, they could have value beyond diabetes prevention alone.
However, access and sustainability are key. Lifestyle programmes require trained staff, time, follow-up and support that fits people’s lives. Programmes are less likely to help if they are difficult to attend, culturally unsuitable or unaffordable.
What remains to be answered
Several questions remain.
Researchers still need to understand which parts of the lifestyle intervention were most important. Weight loss, physical activity, dietary change, social support and regular contact with health professionals may all have contributed.
It is also unclear which groups benefit most. Future studies could examine differences by age, sex, ethnicity, baseline weight, income, medication use and existing health conditions.
Another question is how best to sustain healthy behaviour over many years. The original study offered repeated support, which may not always be available in routine care.
Further research may also look at whether lifestyle programmes reduce the severity of chronic conditions, not just whether diagnoses occur.
The bottom line
This long-term clinical trial suggests that intensive lifestyle support for adults with prediabetes can reduce the risk of developing multiple chronic conditions over time.
The findings do not replace current medical advice and do not mean medication is unnecessary.
They do, however, add weight to the case for practical, sustained lifestyle programmes as part of chronic disease prevention.
For people at risk of diabetes, the message is not that lifestyle change is easy or that it guarantees protection. It is that structured support for healthier eating, regular activity and weight management may improve long-term health in ways that extend beyond diabetes alone.
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