In the early 2000s the U.S. Diabetes Prevention Program (DPP), a large randomized clinical trial, showed that intensive lifestyle modification was better than a medication called metformin at preventing at-risk patients from developing Type 2 diabetes.
In a newly completed follow-up study, a team of researchers including Vallabh "Raj" Shah, professor emeritus in The University of New Mexico Departments of Internal Medicine and Biochemistry & Molecular Biology at the School of Medicine, found that the health benefits from the lifestyle intervention persisted more than 20 years later.
In a paper published in The Lancet Diabetes & Endocrinology, they reported that the greatest results from both interventions were seen in the first few years of the study, and they were durable, Shah said. "The data suggests that those people who didn't get diabetes also didn't get diabetes after 22 years," he said.
The DPP was launched in 1996 to compare the benefits of metformin – then newly approved by the FDA to treat Type 2 diabetes – and a lifestyle modification regimen that included exercise and a healthy diet. The study enrolled 3,234 patients with prediabetes at 30 institutions in 22 states.
The intensive lifestyle intervention reduced the development of diabetes by 24%, and metformin reduced diabetes development by 17%, according to the new study. The DPP had previously found that after the first three years of study, the lifestyle intervention of moderate weight loss and increased physical activity reduced the onset of Type 2 diabetes by 58% compared with a placebo medicine, while metformin reduced development of diabetes by 31%.
Compared with the original placebo group, the median time without diabetes was extended by three-and-a-half years in the lifestyle group and two-and-a-half years in the metformin group.
Within three years, they had to stop the study because lifestyle was better than metformin. That means lifestyle, which everybody is banking on, is more effective – that is the news."
Vallabh "Raj" Shah, professor emeritus in The University of New Mexico
But because a wealth of health and biological data had already been collected for patients participating in the project, the DPP was repurposed into the DPP Outcomes Study (DPPOS), enabling researchers to follow their health outcomes in multiple domains over a period of decades, he said.
Shah has contributed to kidney disease research for more than three decades, conducting multiple studies at Zuni Pueblo and other American Indian communities in western New Mexico. He has also overseen the participation of the American Indian cohort enrolled in the DPPOS. Meanwhile, David Schade, MD, chief of the Division of Endocrinology in the UNM School of Medicine, recruited New Mexico participants in the study.
More recently, he said, DPPOS researchers have taken advantage of their large, well-documented cohort to repurpose the study to focus on diseases associated with aging, such as cancer and dementia, Shah said.
Source:
Journal reference:
Knowler, W. C., et al. (2025). Long-term effects and effect heterogeneity of lifestyle and metformin interventions on type 2 diabetes incidence over 21 years in the US Diabetes Prevention Program randomised clinical trial. The Lancet Diabetes & Endocrinology. doi.org/10.1016/s2213-8587(25)00022-1.