Diabetes: Does a long-term study reinforce or change approaches to prevention?

Two decades ago, the Diabetes Prevention Program (DPP) clearly demonstrated that type 2 diabetes could often be slowed or prevented in people diagnosed with early signs of it (prediabetes). One approach tested was a low-calorie healthy diet combined with at least 150 minutes of activity to help participants lose at least 7% of body weight. Another was metformin therapy, a medicine widely used to treat diabetes. Both were compared to a control group given a placebo (fake) pill.

A recent follow-up study has focused on death rates from cancer, cardiovascular disease, and all causes in subsequent years — and the findings for the three groups were in some ways unexpected.

Why is it important to slow or prevent diabetes?

Type 2 diabetes is one of the most common long-term illnesses worldwide. Over time, it can cause heart disease, nerve damage, eye problems, and kidney problems, raising risks for disability and early death. If laboratory tests show that a person has prediabetes, well-vetted strategies can help them delay the onset of type 2 diabetes, or prevent it. This could allow people to remain healthier for many years.

What did the follow-up study find?

The results from the original study show that lifestyle modification and metformin therapy each very effectively lower risk for developing diabetes in people who have prediabetes. The reduction in risk was 58% and 31%, respectively, compared to the control group.

The original DPP cohort of 3,234 participants was invited to remain in the follow-up observation study known as the Diabetes Prevention Program Outcomes Study (DPPOS). Most participants have now been followed for over two decades, providing a unique opportunity to assess a number of important health outcomes.

The recent analysis looked at participant deaths from any cause, cancer, or cardiovascular disease after 21 years, on average. The researchers found no difference in the death rates in individuals originally assigned to the intensive lifestyle arm and the metformin arm of the study, compared with those originally placed in the control group.

Does this mean that these strategies are not as good as we thought?

Not at all! It is important to put things in perspective to be able to understand these results.

First, all of the original DPP study participants were notified of the benefits of intensive lifestyle modification and metformin, and invited to remain in the observation phase of this program. Since lifestyle modification had the greatest effect, researchers were ethically required to disclose these results to every participant and motivate people to implement these strategies. In fact, lifestyle modification sessions were offered to all participants after the DPP study ended.

It's likely that many participants in the follow-up study incorporated some beneficial changes into their meal plans and physical activity. This would limit the ability to distinguish the effect of intensive lifestyle modification on subsequent health outcomes.

Second, in the initial study only one group took metformin. In the follow-up study, any participant who developed type 2 diabetes was referred to their primary care physician to decide how to manage their blood sugar.

Metformin is the first-line therapy for type 2 diabetes. Therefore, those who developed diabetes were commonly prescribed metformin even if they happened to be in the control group or intensive lifestyle modification group. Over time, the three groups became less well differentiated from one another. In this recent analysis, statistical tests were performed to eliminate this bias without affecting the main results, but some remaining bias cannot be totally dismissed.

Death rates were low overall in the DPPOS

The people who took part in these studies were a fairly healthy group of individuals, and 50 years old, on average, when research began. That helps explain lower than usual death rates compared with findings from international diabetes prevention studies, or even other US studies, on type 2 diabetes.

It's also interesting that cancer — not heart problems, strokes, or other forms of cardiovascular disease — was the leading cause of death in the follow-up study. In the general population, cardiovascular disease has topped the chart for many years.

Widespread strategies to reduce cardiovascular disease in adults may play a role here. Yet this advantage also may diminish the ability to see significant differences in death rates when researchers compare the three groups in the DPPOS.

What should we do with all this information?

The best course is to continue to work toward preventing or delaying diabetes. That's healthy for us as individuals, and for our country collectively. Here's what we know based on research.

If you have prediabetes:

• Intensive lifestyle modification continues to be the best way to reduce risk for developing type 2 diabetes. It can help you avoid or delay diabetes, gain additional benefits linked with weight loss, and lower risk for heart disease and stroke.
• Metformin, an inexpensive, safe medicine with few side effects, also reduces risk for developing diabetes. Metformin is particularly beneficial for people under age 60, people with a body mass index above 35, and women with a history of gestational diabetes.

Let's not forget that many factors may also play a role in determining the best approaches to prevent type 2 diabetes for each person. Age, race and ethnicity, other medical conditions, overall type 2 diabetes risk, and what types of approaches an individual is able to follow are all important factors to consider. If you have diabetes in your family, or have prediabetes or concerns about developing diabetes, talk to your health care team to decide on the best combination of preventive strategies for you.