Lifestyle Intervention Outperforms Metformin in Reducing Long-Term Multimorbidity Risk, Landmark NIH Study Finds

A decades-long clinical trial has delivered a striking verdict: intensive lifestyle changes focused on diet and exercise significantly outperform the widely prescribed diabetes drug metformin查看药品详情 in reducing the long-term risk of developing multiple chronic conditions, according to findings published in JAMA.

The study, an analysis of the landmark Diabetes Prevention Program (DPP) and its follow-up Diabetes Prevention Program Outcomes Study (DPPOS), tracked 1,173 adults at high risk of diabetes from 1996 through 2021. Researchers found that participants assigned to a rigorous lifestyle intervention — a low-fat, low-calorie diet combined with at least 150 minutes of physical activity per week — experienced a substantially lower burden of multimorbidity (搜索)搜索该疾病 over more than two decades of follow-up compared to those receiving metformin查看药品详情 or placebo.

"Multimorbidity (搜索)搜索该疾病 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 (NIA). "Our work showing that healthy lifestyle intervention can significantly lower the burden of multimorbidity is a step forward in addressing this growing problem."

Metformin查看药品详情 fails to show benefit over placebo

Metformin查看药品详情, a decades-old generic medication that has generated considerable excitement for its potential anti-aging effects and ability to reduce risks ranging from long COVID to Type 2 diabetes (搜索)搜索该疾病, did not demonstrate a statistically significant reduction in multimorbidity (搜索)搜索该疾病 risk compared to placebo in this analysis.

By the end of the 21-year follow-up period, 85% of all study participants had developed two or more chronic conditions. The breakdown across groups was telling: 82% in the lifestyle intervention group developed multimorbidity (搜索)搜索该疾病, compared with 85% in the metformin查看药品详情 group and 87% in the placebo group.

Compared with placebo, participants in the lifestyle intervention had a 21% lower risk for developing two chronic conditions and a 25% lower risk for three chronic conditions. These results held even when diabetes was excluded from the multimorbidity (搜索)搜索该疾病 definition, underscoring that the benefits extended well beyond glycemic control.

Study design and multimorbidity (搜索)搜索该疾病 tracking

The original DPP trial, conducted at 27 sites across the United States from 1996 to 1999, randomly assigned 3,234 adults with prediabetes (搜索)搜索该疾病 to intensive lifestyle intervention, metformin查看药品详情, or placebo for three years. Participants were then enrolled in the DPPOS and followed through 2021. The current analysis focused on 1,173 participants who were enrolled in Medicare and consented to linkage of their Centers for Medicare & Medicaid Services (CMS) claims.

Researchers examined 15 common chronic conditions tracked in Medicare data, including hypertension, heart disease, stroke, arthritis, chronic kidney disease, COPD, cancer, depression, dementia, osteoporosis, and diabetes.

In the lifestyle arm, participants received 16 individual intervention sessions followed by monthly sessions for approximately two years. The behavior change program targeted reduced calorie and fat intake and at least 150 minutes of weekly physical activity to achieve 7% or greater weight loss from baseline. After the initial trial, all participants were offered the intensive lifestyle curriculum in group settings, with original lifestyle participants receiving booster sessions twice annually during the outcomes study phase.

Clinical implications for an aging population

The findings arrive at a critical juncture. As America's population continues to age, multimorbidity (搜索)搜索该疾病 has become increasingly prevalent among adults 65 and older, and preventing or delaying its onset is considered one of the most pressing challenges in modern healthcare. The study authors noted that efforts to prevent or slow multimorbidity have largely fallen short in real-world medicine, as conditions tend to feed into one another over time.

The researchers also highlighted the growing prevalence of "high-cost condition dyads" — combinations such as heart failure and kidney disease, or cancer paired with mental health conditions — which account for a disproportionate share of healthcare spending and complexity.

"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 healthcare spending."

Dr. Shirin Jaggi, DO, an endocrinologist at Northwell Health who was not involved in the study, described the findings as "powerful," noting that she can now tell patients "it's not just a pill that I need to give you." She emphasized that lifestyle changes are not one-size-fits-all and stressed the importance of gradual adoption. "We have to start slow and work our way up to it," Dr. Jaggi said, recommending frequent check-ins with patients to monitor progress. "For somebody who's been sedentary, we work slowly, whether that means including 10 to 15 minutes once or just twice a day, and then working our way up."

"For me to be able to tell patients that there is something they can do beyond prescription, which could be even more powerful than a prescription, I think it's amazing," Dr. Jaggi added. "I think it gives patients motivation."