Midlife weight loss may lower your long-term risk of diabetes, study finds

By Dr. Liji Thomas, MDReviewed by Lauren HardakerMay 29 2025

A decades-long study reveals that shedding extra weight in midlife, without medication or surgery, could reduce your risk of serious illness and help you live longer.

Study: Weight Loss in Midlife, Chronic Disease Incidence, and All-Cause Mortality During Extended Follow-Up. Image credit: goffkein.pro/Shutterstock.com

A recent paper published in the journal JAMA Network Open examined the benefits of sustained weight reduction in midlife, going beyond the established reduction in diabetes risk.

Introduction

Morbid obesity is treated both medically and surgically. Newer drugs, like glucagon-like peptide one receptor agonists (GLP-1 RAs), and bariatric surgery induce significant weight loss. While these reduce chronic disease and death risks, they carry their risks.

Overweight and obese people cut their risk of diabetes mellitus when they lose weight. The change in the risk of other chronic diseases is still unclear, perhaps because of poor study design and inadequate study periods. For instance, reduced cardiovascular and total mortality after six years of lifestyle modification may only manifest three decades later.

The current study addressed healthy people between 40 and 50 (midlife) who lost weight, as measured by changes in their body mass index (BMI), without pharmacological or surgical interventions. Their risk of chronic disease and/or death was measured over several decades.

The study included 23,149 adults from three cohorts with height and weight measured over 12-35 years. These were the 1985-1988 Whitehall II study (WHII), the 1964-1973 Helsinki Businessmen Study (HBS), and the 2000 Finnish Public Sector study (FPS). 

They were classified into four groups: those with a stable BMI at <25 (persistent healthy weight), those with a BMI change from 25 or more to <25 (weight loss), BMI change from <25 to 25 or more (weight gain), and those who had a stable BMI at 25 or more (persistent overweight).

Study findings

Overall, overweight adults who lost enough weight to become healthy, and kept it off, had a lower risk of chronic disease. This was independent of the change in type 2 diabetes risk. They also had a lower risk of death from all causes compared with those who remained overweight.

In the WHII and HBS cohorts, BMI trajectories remained stable up to ages 66 and 80 respectively. Approximately 5% and 9% of participants, respectively, were classified as obese (BMI ≥30) at one or both early evaluations, indicating a population largely free from morbid obesity at baseline.

Compared to overweight participants, WHII participants who lost or kept within a healthy weight had a 50% lower risk of developing one or more chronic diseases over a median of 23 years of follow-up. After adjusting for the effect of decreased diabetes risk, chronic disease risk remained 40% lower. This may be partly explained by the lower mean blood pressure and total cholesterol levels among those who lost weight.

In the FPS cohort, those who lost weight had a 60% reduction in the risk of chronic disease over a median of 12 years. The HBS participants had a 20% lower risk of death over a median follow-up of 35 years. The median survivor age was 91 years at the end of the study.

Participants who gained weight from a healthy to overweight BMI also had an elevated risk of chronic disease compared to those with persistent healthy weight, though lower than those with persistent overweight.

Evidence

By choosing cohorts of healthy people with a relatively lower median age, the analysis excluded confounding due to unintentional weight loss. Unintended weight loss is often associated with frailty due to disease, old age, or cancer, so it is usually a marker of increased mortality risk.

Other studies have repeatedly demonstrated a reduced diabetes risk among people who intentionally lose weight, including those who are treated with drugs or surgery. There has not been consistent evidence of marked differences in cardiovascular risk or mortality.

This may be because medical or surgical interventions cause larger weight loss. Again, control groups may be on statins or other drugs that improve cardiovascular risk.

Moreover, healthy but overweight people have a comparable mortality risk with healthy-weight individuals. Above all, follow-up periods that are too short prevent the detection of long-term benefits to health and mortality risk.

These findings may not be generalizable to morbidly obese people, who are usually the subjects of bariatric surgery or weight loss drugs. In such people, weight loss may involve the loss of lean (muscle) mass, which could pose a risk to health over time.

The FPS cohort used self-reported BMI data, which introduces some limitations compared to the measured data used in the other studies. This study did not assess whether weight loss was intentional, though researchers inferred it likely was, based on participant age and health status.

Research in this field should attempt to cover the whole life course, since obesity or being overweight in childhood predicts a higher risk of ischemic heart disease unless the weight is normalized during adolescence.

The study did not directly assess whether weight loss was intentional. Still, because participants were free of diagnosed disease and relatively young, the authors infer that the weight loss was likely deliberate and due to lifestyle changes.

Conclusion

The study found that individuals who reduced their weight from overweight to a healthy range during midlife, without medications or surgery, experienced meaningful long-term health benefits. These included a lower risk of developing chronic diseases and, in some cases, a reduced risk of death.

The benefits persisted even when the reduced risk of diabetes was accounted for, suggesting health benefits beyond lowering diabetes risk. Although sustained weight loss through lifestyle changes can be challenging, the findings highlight its potential to improve long-term health outcomes when initiated in midlife significantly.

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