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Evevident
Original paper
2002NEJMEndocrinology/Metabolism

Diabetes Prevention Program

Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin

RCTPrevention / diabetes

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Overview

In high-risk adults with impaired glucose regulation, intensive lifestyle intervention prevented diabetes more effectively than metformin.

Clinical takeaway

The Diabetes Prevention Program established weight loss, diet, and physical activity as highly effective diabetes-prevention therapy, with metformin as a useful but less potent option in selected patients.

Key result

Lifestyle intervention reduced diabetes incidence by 58% and metformin by 31% versus placebo.

Practice impact

Lifestyle intervention is first-line diabetes prevention in prediabetes; metformin is considered for selected high-risk patients.

Evidence

Study design

Randomized controlled trial (three arms).

Enrollment

3,234

Follow-up

Average 2.8 years; stopped early for efficacy.

Geography

United States

Clinical question

Can lifestyle intervention or metformin prevent progression to type 2 diabetes in high-risk adults?

Population

  • Adults at high risk for diabetes with elevated fasting and post-load glucose and overweight/obesity (mean BMI 34).

Intervention

Intensive lifestyle intervention (>=7% weight loss and >=150 min/week activity) or metformin 850 mg twice daily.

Comparator

Placebo with standard lifestyle recommendations.

Primary outcome

Development of diabetes.

Intensive lifestyle intervention cut the incidence of type 2 diabetes by 58%, outperforming both metformin (31% reduction) and placebo.

Relative risk reduction (lifestyle vs placebo) / 58 / CI 95% CI 48-66% / p=<0.001

Key results

  • Diabetes incidence: 4.8, 7.8, and 11.0 cases per 100 person-years in the lifestyle, metformin, and placebo groups.
  • Lifestyle intervention reduced diabetes incidence by 58% (95% CI 48-66%) versus placebo.
  • Metformin reduced diabetes incidence by 31% (95% CI 17-43%) versus placebo.
  • Lifestyle intervention was significantly more effective than metformin (NNT over 3 years: 6.9 for lifestyle vs 13.9 for metformin).

Harms

  • Gastrointestinal symptoms were more common with metformin than with lifestyle intervention or placebo.
  • Musculoskeletal symptoms were more common in the lifestyle group given the exercise goals.

Clinical Use

When to cite

  • When counseling patients with prediabetes about lifestyle intervention and metformin for diabetes prevention.

Practice impact

  • Lifestyle intervention is first-line diabetes prevention in prediabetes; metformin is considered for selected high-risk patients.

Applicability

  • Most applicable to adults with prediabetes (elevated fasting and post-load glucose) and overweight or obesity.

Limitations

  • Resource-intensive lifestyle program may be hard to replicate outside a trial.
  • Enrolled patients with impaired glucose regulation and overweight/obesity, not the general population.
  • Prevention or delay of diabetes was the endpoint; the main trial was not powered for cardiovascular or mortality outcomes.

Common misinterpretations

  • DPP shows prevention or delay of diabetes; long-term follow-up (DPPOS) showed the effect attenuates but persists.
  • Metformin was less effective overall and worked best in younger, more obese participants with higher fasting glucose.

Related evidence

UKPDS - Same Disease

Citation

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(6):393-403. doi:10.1056/NEJMoa012512

Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.