For people with prediabetes, lifestyle changes like diet, exercise, and weight loss are significantly more effective at preventing multiple chronic diseases than the medication metformin. A major 21-year study found that participants who made these lifestyle modifications developed fewer chronic conditions overall, suggesting that prevention strategies should prioritize behavioral changes over medication alone.

What Is Prediabetes and Why Does It Matter?

Prediabetes is a condition where blood sugar levels are higher than normal but not yet high enough to be diagnosed as type 2 diabetes. According to the Centers for Disease Control and Prevention, more than 2 in 5 adults in the United States have prediabetes. Without intervention, prediabetes often progresses to type 2 diabetes and increases the risk of heart disease, stroke, and many other chronic conditions.

The real concern isn't just diabetes itself. People with prediabetes often develop multimorbidity, which means having two or more chronic conditions at the same time. This combination of diseases significantly reduces quality of life and complicates medical care as people age.

How Did Researchers Compare Lifestyle Changes to Metformin?

Researchers analyzed data from 1,173 people who participated in the Diabetes Prevention Program (DPP) and its follow-up study (DPPOS) over 21 years. Participants were randomly assigned to one of three groups: a lifestyle intervention program, metformin (a common type 2 diabetes medication), or a placebo.

The lifestyle intervention group received 16 individual counseling sessions followed by monthly sessions for about two years. These sessions focused on reducing calorie and fat intake, increasing physical activity, and achieving weight loss. The metformin group took 850 milligrams of the medication twice daily, while the placebo group received a dummy pill. Both the metformin and placebo groups also received lifestyle advice four times per year.

At the start of the study, participants had a median age of 51 years and a median body mass index (BMI) of 32.1, which falls into the obesity category. The group was diverse, with 56 percent non-Hispanic white, nearly 25 percent non-Hispanic Black, and the remainder Hispanic, Asian/Pacific Islander, and Native American.

What Were the Key Findings on Chronic Disease Prevention?

After 21 years of follow-up, 85 percent of all participants had developed multimorbidity. However, the number of chronic conditions differed significantly between groups. In the placebo and metformin groups, participants had a median of 5 chronic conditions, whereas in the lifestyle intervention group, the median was 4.

When researchers looked at the severity of multimorbidity, the differences became even clearer. While 81 percent of both the placebo and metformin groups had more than 3 chronic conditions, only 72 percent of the lifestyle group did. This translates to a 21 percent reduction in the risk of developing multiple chronic conditions in the lifestyle group compared to the other groups.

The most common chronic conditions across all groups were high cholesterol (76 percent), high blood pressure (75 percent), and diabetes (67 percent). However, the lifestyle intervention group consistently had lower rates of developing additional conditions beyond these.

Why Does Lifestyle Work Better Than Medication?

The key difference lies in how broadly each approach affects the body. Metformin primarily works by improving insulin sensitivity and reducing glucose production by the liver. Lifestyle changes, by contrast, influence multiple biological pathways simultaneously.

"Lifestyle interventions are likely more effective because they target several different biological pathways simultaneously, rather than focusing on a single aspect of a disease. Metformin is an important and effective medication that primarily improves insulin sensitivity and reduces glucose production by the liver. Lifestyle changes are multifaceted and influence far more than blood sugar," said Thomas M. Holland, Physician Scientist and Assistant Professor at the Department of Internal Medicine, RUSH Institute for Healthy Aging in Chicago.

Thomas M. Holland, Physician Scientist and Assistant Professor, Department of Internal Medicine, RUSH Institute for Healthy Aging

From a biological perspective, healthy lifestyle behaviors can reduce chronic inflammation, improve how the body uses insulin, support blood vessel health, optimize blood pressure, preserve muscle mass, and promote healthy brain aging. Since many chronic diseases share common underlying pathways, improving lifestyle produces benefits that extend well beyond any single diagnosis.

What Specific Lifestyle Changes Should People Make?

The lifestyle intervention in this study focused on three main components:

• Dietary Changes: Reducing calorie and fat intake while emphasizing whole foods like fruits, vegetables, legumes, whole grains, healthy fats, and lean proteins while reducing highly processed foods.
• Physical Activity: Aiming for at least 150 minutes of exercise per week, which could include longer daily walks or resistance training incorporated into a regular routine.
• Weight Loss: Achieving meaningful weight reduction through the combination of diet and exercise changes.

Beyond these core components, experts also emphasize the importance of sleep quality, stress management, and strengthening social connections, as these factors influence the biological processes that drive chronic disease development.

How to Start Making Lifestyle Changes for Prediabetes Prevention

• Begin with Dietary Assessment: Review your current eating patterns and identify highly processed foods to reduce. Start incorporating more whole grains, vegetables, lean proteins, and healthy fats into meals gradually rather than making drastic overnight changes.
• Establish a Regular Exercise Routine: Aim for at least 150 minutes of moderate physical activity per week, which can be broken into 30-minute sessions on five days. This could include brisk walking, swimming, cycling, or resistance training depending on your fitness level and preferences.
• Set Realistic Weight Loss Goals: Work with a healthcare provider or registered dietitian to determine a healthy target weight and create a sustainable plan to reach it over time, typically aiming for gradual loss rather than rapid changes.
• Address Sleep and Stress: Prioritize seven to nine hours of quality sleep per night and incorporate stress management techniques like meditation, yoga, or time in nature, as these support the biological mechanisms that prevent chronic disease.
• Build Social Support: Engage with friends, family, or support groups who share similar health goals, as social connections have been shown to influence long-term health outcomes and motivation.

What Does This Mean for Diabetes Prevention?

This research represents a significant shift in how experts think about preventing chronic disease. Rather than focusing narrowly on preventing a single disease like type 2 diabetes, the study demonstrates that lifestyle interventions promote long-term health across multiple organ systems.

"One of the most encouraging aspects of this study is the reminder that chronic disease is not simply an inevitable consequence of aging. While aging itself is unavoidable, many of the biological processes that contribute to chronic disease can be influenced by the choices we make throughout life," noted Thomas M. Holland.

Thomas M. Holland, Physician Scientist and Assistant Professor, Department of Internal Medicine, RUSH Institute for Healthy Aging

For most people, the takeaway is straightforward: the same habits that help prevent diabetes are often the same habits that protect the heart, brain, and overall health and quality of life. This means that investing in lifestyle changes now can have far-reaching benefits that extend well into older age.

While medications like metformin remain important tools and can be lifesaving for some people, this research underscores that lifestyle factors should be the foundation of chronic disease prevention. For anyone with prediabetes or at risk of developing it, these findings suggest that prioritizing diet, exercise, and weight loss offers the best chance of maintaining long-term health and avoiding the burden of multiple chronic conditions.