A 21-year follow-up reported in an NIH announcement found that adults with prediabetes who were assigned to a lifestyle program had a lower long-term risk of developing multiple chronic diseases. The findings were published in JAMA and came from a major clinical trial supported by the National Institutes of Health.
The result adds a longer view to one of the most familiar pieces of health advice: change what you eat, move more and lose weight when risk is high. In this study, that advice was delivered as a structured program, then followed across decades. The researchers found that people assigned to the lifestyle intervention had a significantly lower risk of multimorbidity than those assigned to placebo.
The trial also carried a second message. Participants assigned to metformin, a widely used diabetes drug, did not show a statistically significant reduction in multimorbidity risk compared with placebo. The finding gives researchers a sharper look at which early interventions may shape health later in life.
A Long Look at Prediabetes
The study centered on adults with prediabetes, a condition in which blood sugar is elevated and the risk of type 2 diabetes is higher. The participants were also at high risk of diabetes when they entered the original Diabetes Prevention Program between 1996 and 1999.
Researchers followed a subset of 1,173 participants who were enrolled in Medicare and consented to linkage with Centers for Medicare & Medicaid Services claims. That long follow-up allowed the team to examine chronic disease patterns through 2021. The study took place across 27 sites in the United States.
That timeline is important because chronic diseases often accumulate slowly. A person can move from one diagnosis to two or three over many years. Researchers use the term multimorbidity when someone has multiple chronic health conditions at the same time.
“Multimorbidity is a common issue and few interventions have been found to prevent or delay developing multiple chronic conditions,” said Marcel Salive, M.D., first author of the study from NIH’s National Institute on Aging. His comment points to the public-health challenge behind the trial. Many older adults live with overlapping conditions that complicate care and reduce quality of life.
The Lifestyle Program
The original Diabetes Prevention Program randomly assigned participants to one of three groups: an intensive lifestyle intervention, metformin, or placebo. The lifestyle arm received a structured behavior-change program. It focused on food, activity and weight loss.
During the first phase, lifestyle participants were offered 16 individual sessions followed by monthly sessions for about two years. The program targeted reduced calories and fat. It also aimed for at least 150 minutes of physical activity each week.
The weight-loss target was at least 7% of baseline body weight. For many people, that kind of goal can sound modest beside extreme diet claims. In a clinical setting, it can still change metabolic risk in meaningful ways.
After the first Diabetes Prevention Program ended, all participants were offered the intensive lifestyle curriculum in groups during a six-month bridge period. During the Diabetes Prevention Program Outcomes Study, all participants were offered quarterly group lifestyle sessions. Those originally assigned to lifestyle also received booster sessions twice a year.
Lower Risk for Multiple Conditions
By the end of follow-up, chronic disease had become common across the study population. Overall, 85% of participants had developed two or more chronic conditions. The rates were 82% in the lifestyle group, 85% in the metformin group and 87% in the placebo group.
Compared with placebo, the lifestyle intervention was linked to a 21% lower risk for developing two chronic conditions. It was also linked to a 25% lower risk for developing three chronic conditions. Those figures suggest that early behavior support may influence how disease burden builds over time.
“Our work showing that healthy lifestyle intervention can significantly lower the burden of multimorbidity is a step forward,” Salive said. The result is especially striking because the analysis looked beyond diabetes alone. The benefits persisted even when diabetes was removed from the definition of multimorbidity.
Across all three groups, aging still brought a high burden of chronic conditions. Even with that reality, the lower risk in the lifestyle group suggests that diet, exercise and weight-loss support may shift the pace of that accumulation.
Metformin’s Neutral Result
The metformin group gave researchers a useful comparison. Metformin has long been used in the management of type 2 diabetes. Earlier research from the Diabetes Prevention Program showed that both metformin and lifestyle intervention can help prevent or delay diabetes.
In this analysis, participants assigned to metformin did not experience a statistically significant reduction in multimorbidity risk. That finding applies to the outcome measured here, which was the development of multiple chronic conditions over time.
The distinction matters for patients and clinicians. A medicine may help with one disease pathway while producing a different pattern when researchers track many chronic diagnoses together. The NIH-supported trial was designed to ask that broader question across a long period.
Because the study used random assignment during the original trial, it offers stronger evidence than many observational studies. The later follow-up used Medicare claims to track diagnoses over time. Claims data can capture broad patterns across many conditions, although they also depend on what gets diagnosed and recorded in medical care.
The 15 Diseases Researchers Tracked
The researchers examined 15 chronic conditions commonly tracked in Medicare data. The list included hypertension, heart disease, stroke, arthritis, chronic kidney disease, chronic obstructive pulmonary disease, cancer, depression, dementia, osteoporosis and diabetes. The NIH announcement also described the list as a set of common conditions used to measure multimorbidity in older adults.
This approach helped the team look at the body as a connected system. Prediabetes is tied to metabolism, weight, blood vessels, inflammation and many other processes. A lifestyle program that changes energy intake and physical activity can touch several of those pathways at once.
Exercise can improve how muscles use glucose. Weight loss can reduce strain on insulin-producing systems. Dietary changes can affect blood pressure, lipids and overall metabolic health. Over decades, those shifts may influence the appearance of several diagnoses.
The study’s design also reflects a practical reality of aging. Many people seek medical care for clusters of conditions rather than a single isolated disease. Tracking multiple diagnoses gives researchers a view that is closer to what older adults and clinicians manage every day.
Why the Findings Matter for Aging
The findings are especially relevant as more adults live into older age with long-term health conditions. Multimorbidity can mean more medications, more clinic visits and more complex treatment decisions. Preventing or delaying that buildup could ease pressure on patients and health systems.
Griffin P. Rodgers, M.D., director of NIH’s NIDDK, called the results “highly encouraging.” He added that “lifestyle programs focused on diet and exercise may persistently lower the risk of developing multiple chronic conditions, beyond diabetes.”
The word persistently carries weight here. The intervention began in the 1990s, while the follow-up extended through 2021. That long span gives the study unusual relevance for aging research because it connects midlife or later-life risk reduction with health outcomes years later.
The study also supports the value of structured programs rather than vague advice. Participants in the lifestyle group received sessions, goals and ongoing reinforcement. That kind of framework can help people turn general recommendations into repeatable habits.
For people with prediabetes, the message is practical and cautious. Diet, activity and modest weight loss can have benefits that reach beyond blood sugar. The NIH-supported trial suggests that early lifestyle support may help slow the long cascade of chronic disease that often shapes aging.
