A landmark clinical trial supported by the National Institutes of Health and published on June 15, 2026, in the Journal of the American Medical Association has found that adults with prediabetes who participated in an intensive lifestyle intervention had a 25% lower risk of developing three or more serious chronic conditions over more than 20 years of follow-up — a finding that provides the most durable evidence to date that lifestyle change is not merely a wellness strategy but a powerful medical prevention tool.
The study arrives at a moment when approximately 96 million American adults — more than one in three — are living with prediabetes, and when chronic disease multimorbidity has become one of the costliest and most debilitating health challenges in the United States.
What the Study Found — and Why It Matters
The study, published online June 15, 2026 in JAMA under the citation “Lifestyle and Metformin Interventions and Risk of Multimorbidity in Adults With Prediabetes,” analyzed data from participants in the Diabetes Prevention Program Outcomes Study — a landmark multi-decade follow-up to the original Diabetes Prevention Program (DPP) trial. Lead author Marcel E. Salive, M.D., of the NIH’s National Institute on Aging, and colleagues tracked participants across more than two decades, examining 15 chronic conditions commonly monitored in Medicare data.
The conditions tracked included hypertension, heart disease, stroke, arthritis, chronic kidney disease, COPD, cancer, depression, dementia, osteoporosis, and diabetes itself. The results were striking:
- Compared to participants in the placebo group, those in the lifestyle intervention group had a 21% lower risk of developing two or more chronic conditions and a 25% lower risk of developing three or more chronic conditions
- The protective effect persisted even when diabetes was removed from the multimorbidity definition — meaning the benefits extended well beyond diabetes prevention
- Participants assigned to metformin — a first-line diabetes medication — did not experience a statistically significant reduction in multimorbidity risk
The lifestyle intervention targeted a 7% reduction in body weight and at least 150 minutes of moderate-intensity physical activity per week, achieved through 16 sessions with a trained lifestyle coach in the first year and ongoing support thereafter.
Study Finding
Data
Published
JAMA, June 15, 2026
Study type
Randomized clinical trial with 20+ year follow-up (DPPOS)
Conditions tracked
15 (hypertension, heart disease, stroke, CKD, cancer, depression, dementia, and more)
Lifestyle group: risk reduction for 2+ conditions
21% lower vs. placebo
Lifestyle group: risk reduction for 3+ conditions
25% lower vs. placebo
Effect persistent after removing diabetes
Yes
Metformin group result
No statistically significant reduction
Lifestyle targets
7% weight loss + 150 min/week moderate activity
U.S. adults with prediabetes
~96 million (1 in 3+)
Awareness rate among those with prediabetes
Majority unaware
Why This Finding Goes Beyond Diabetes Prevention
Multimorbidity — the simultaneous presence of two or more chronic conditions — is the defining health challenge of an aging America. According to Medicare data, the majority of Americans over 65 have five or more chronic conditions. Managing multiple conditions simultaneously drives the majority of U.S. healthcare spending, reduces quality of life, complicates treatment, and increases mortality risk.
“Multimorbidity is a common issue, and few interventions have been found to prevent or delay developing multiple chronic conditions,” said Dr. Marcel Salive of the NIH’s National Institute on Aging.
What makes the new JAMA study’s finding significant is that the lifestyle intervention’s protection was not simply a downstream consequence of preventing diabetes. When researchers removed diabetes from the multimorbidity count — asking whether the lifestyle intervention protected against heart disease, kidney disease, depression, and other conditions independently — the protective effect remained. This suggests that the mechanisms at work go beyond blood sugar control: the weight loss, physical activity, and behavioral changes appear to reduce systemic inflammation, improve cardiovascular function, support kidney health, and possibly reduce cancer risk through multiple pathways simultaneously.
“These findings are highly encouraging, reinforcing that lifestyle programs focused on diet and exercise may persistently lower the risk of developing multiple chronic conditions, beyond diabetes,” said Griffin P. Rodgers, M.D., Director of NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). “Furthermore, because lifestyle modifications can be safe and cost-effective, sustaining these healthy behaviors among people at risk of diabetes may help reduce not only the individual health burden but also broader health care spending.”
The metformin finding warrants attention. Metformin is widely used in prediabetes management, and the drug did not produce a statistically significant reduction in multimorbidity risk in this study — suggesting that medication alone is not equivalent to lifestyle change when it comes to preventing the broader cascade of chronic conditions.
Who Has Prediabetes — and Who Is Most at Risk
Prediabetes is defined by blood sugar levels that are above normal but below the diagnostic threshold for type 2 diabetes — typically a fasting blood glucose of 100 to 125 mg/dL or an HbA1c of 5.7% to 6.4%. Most people with prediabetes have no symptoms, which is precisely why an estimated 80% of those who have it are unaware.
The CDC estimates that without intervention, 15% to 30% of people with prediabetes will develop type 2 diabetes within five years. But the JAMA study makes clear that the health risks of prediabetes extend far beyond diabetes progression. The same metabolic dysfunction driving elevated blood sugar — insulin resistance, chronic low-grade inflammation, excess visceral fat — also elevates risk for heart disease, kidney disease, hypertension, and several cancers.
Risk is not evenly distributed. Prediabetes is more common among people who are overweight or obese, physically inactive, have a family history of type 2 diabetes, are over 45, have had gestational diabetes, or have certain conditions including polycystic ovary syndrome. Communities of color — particularly Black, Hispanic, and American Indian/Alaska Native adults — face higher rates of both prediabetes and progression to type 2 diabetes, driven in part by structural barriers to healthy food and safe physical activity.
What Residents Can Do Right Now — The National DPP
The CDC’s National Diabetes Prevention Program (National DPP) brings evidence-based lifestyle change programs to communities across the country at low or no cost. Based on the original DPP trial, the program delivers the same intervention — weight loss goals, physical activity targets, and behavioral coaching — through in-person and online programs offered at hundreds of sites nationwide, including hospitals, community health centers, pharmacies, and YMCAs.
People can find a National DPP location at CDC.gov/diabetes/prevention. Many programs are now covered by Medicare and an increasing number of private insurers. A simple blood test — available through any primary care provider — can determine prediabetes status.
The first step is knowing your blood sugar numbers. Given that 80% of people with prediabetes are unaware, the most urgent public health action available is routine screening — particularly for adults over 35 who are overweight or have any of the known risk factors.
Frequently Asked Questions
What did the NIH/JAMA prediabetes study find?
Published June 15, 2026 in JAMA, the study found that an intensive lifestyle intervention — targeting 7% weight loss and 150 minutes weekly of moderate physical activity — reduced the risk of developing three or more serious chronic conditions by 25% over more than 20 years, compared to placebo. The benefit persisted even after diabetes was excluded from the count.
What does “multimorbidity” mean?
Multimorbidity refers to the simultaneous presence of two or more chronic health conditions. The study tracked 15 conditions including heart disease, hypertension, stroke, chronic kidney disease, cancer, depression, dementia, and others. Developing multiple conditions at once dramatically increases healthcare costs, complexity of treatment, and mortality risk.
Did metformin produce the same results as lifestyle change?
No. Participants assigned to metformin did not experience a statistically significant reduction in multimorbidity risk. This suggests that lifestyle change — weight loss, physical activity, and behavioral change — acts through mechanisms that medication alone does not fully replicate.
How do I know if I have prediabetes?
Prediabetes typically has no symptoms. It is detected through a blood test: a fasting blood glucose of 100–125 mg/dL or an HbA1c of 5.7%–6.4%. The CDC recommends screening for all adults 35 and older who are overweight or have risk factors. Ask your primary care provider.
What is the CDC’s National Diabetes Prevention Program?
The National DPP is a network of evidence-based lifestyle change programs available at hundreds of sites nationally, including hospitals, community health centers, pharmacies, and YMCAs. It targets 5–7% weight loss and 150 minutes of weekly activity. Many programs are now covered by Medicare. Find a program at CDC.gov/diabetes/prevention.
