Lifestyle intervention linked to lower long-term multimorbidity in adults with prediabetes

A 21-year follow-up of the Diabetes Prevention Program suggests that early lifestyle intervention may have benefits beyond delaying type 2 diabetes.

Adults with prediabetes who received an intensive lifestyle intervention in the Diabetes Prevention Program were less likely to develop multiple chronic conditions over long-term follow-up than those assigned to placebo, according to an analysis published in JAMA.¹ A similar reduction was not observed with metformin.

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Prediabetes is a major focus for endocrinologists because it identifies people at increased risk of type 2 diabetes and broader cardiometabolic disease. While diabetes prevention remains a central goal, the new analysis examined whether early intervention could also affect the longer-term accumulation of chronic disease.

What did the study investigate?

Researchers used long-term follow-up data from the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study² to examine multimorbidity among participants who had Medicare data available. Multimorbidity was defined as two or more chronic conditions from a list of 15 conditions recorded in Centers for Medicare & Medicaid Services data.¹

The original trial enrolled 3,234 adults at high risk of diabetes between 1996 and 1999 and randomly assigned them to intensive lifestyle intervention, metformin, or placebo.² This analysis focused on 1,173 participants with Medicare morbidity data available through 2021.¹

What do the data show?

After up to 21 years of follow-up, 997 of 1,173 participants had developed multimorbidity. The proportion was lowest in the lifestyle group, affecting 316 of 385 participants, compared with 327 of 385 in the metformin group and 350 of 403 in the placebo group. This corresponded to rates of 82%, 85%, and 87%, respectively.¹

After adjustment for relevant covariates, assignment to lifestyle intervention was associated with a lower risk of multimorbidity compared with placebo (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.68–0.93). Metformin was not associated with a significant reduction compared with placebo (HR, 0.91; 95% CI, 0.78–1.07).¹

The lifestyle association remained when diabetes was not counted as one of the chronic conditions. In an analysis focused on dyads of the costliest conditions, lifestyle intervention was also associated with lower risk than placebo (HR, 0.57; 95% CI, 0.38–0.85).¹

Limitations and caution

The findings come from an observational follow-up of a randomized clinical trial and were limited to participants who consented to linkage with Medicare morbidity data. The analysis also relied on claims-based definitions of chronic disease, and the cohort may not fully reflect all adults with prediabetes seen in routine clinical practice.

Clinical takeaway

These findings suggest that lifestyle intervention in adults with prediabetes may have long-term value beyond delaying diabetes onset, with possible benefits for reducing wider chronic disease burden. For endocrinologists, the study reinforces lifestyle intervention as a core prevention strategy, while suggesting that multimorbidity may be an important outcome to consider in long-term diabetes prevention research.

References

1. Salive ME, Tjaden AH, Ames JR, et al. Lifestyle and metformin interventions and risk of multimorbidity in adults with prediabetes. JAMA. Published online June 15, 2026. doi:10.1001/jama.2026.8492
2. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393–403.