**Background:** The prevention of type 2 diabetes (T2D) was discussed in scientific literature as early as 100 years ago, but rigorous randomized controlled trials (RCTs) were not conducted until the 1990s. Successful prevention requires agreed diagnostic criteria, knowledge of risk factors and natural history, affordable screening methods, and effective interventions for modifiable risk factors. This narrative review summarizes the original proof-of-concept RCTs, their long-term follow-up, and the translation of findings into real-world national prevention programs.
**Methods:** The authors review five landmark proof-of-concept RCTs: the Da Qing IGT and Diabetes Study (China, 6 years, n=577), the Finnish Diabetes Prevention Study (DPS, Finland, 3.2 years, n=522), the Diabetes Prevention Program (DPP, USA, 2.8 years, n=3234), the Japanese Trial of Men with IGT (Japan, 4 years, n=102 intervention, 356 control), and the Indian Diabetes Prevention Programme (IDPP-1, India, 2.5 years, n=531). All trials enrolled people with IGT and tested lifestyle interventions (diet, physical activity, weight loss) with or without metformin. The review also covers implementation programs including Finland's FIN-D2D (2003–2008), the US National DPP (established 2010), the UK NHS DPP (initiated 2016), the European DE-PLAN project, and studies in low- and middle-income countries (LMICs).
**Key Results:** The proof-of-concept RCTs showed relative risk reductions in T2D incidence of 33% (Da Qing diet), 47% (Da Qing exercise), 38% (Da Qing combined), 58% (DPS), 58% (DPP lifestyle), 31% (DPP metformin), 67% (Japanese trial), 29% (IDPP-1 lifestyle), 26% (IDPP-1 metformin), and 28% (IDPP-1 combined). In the DPS, none of the participants who achieved all five lifestyle targets developed T2D during the trial. Long-term follow-up showed sustained benefits: the Da Qing trial found a 49% reduction in T2D incidence over 30 years; the DPS showed an additional 36% risk reduction during the post-intervention period after 3 years and 39% after 9 years. A meta-analysis of post-trial follow-up showed a 20% risk reduction. Real-world implementation programs achieved more modest results: the US NDPP reported median weight loss of 5%; the UK NHS DPP found average weight loss of 3–5 kg and HbA1c reduction of 1.3 mmol/mol after one year. In the Finnish FIN-D2D, individuals with ≥5% weight loss at 1 year had 69% lower diabetes risk, and those with 2.5–4.9% weight loss had 28% lower risk. Over an average 7.4-year follow-up, risk reduction of drug-treated diabetes was approximately 30% in those with >2.5% weight loss after one year. A systematic review of real-world studies showed a pooled relative risk reduction of 0.71 (95% CI 0.58, 0.88) and absolute risk reduction of approximately 3% in the first 1–2 years, compared with approximately 17% in the proof-of-concept trials. In LMICs, a meta-analysis of 14 studies found lifestyle interventions reduced T2D incidence by 25% on average. Cost-effectiveness analyses showed that lifestyle interventions in high-risk individuals are cost-effective, and population-level policies such as sugar-sweetened beverage taxes are cost-saving. The Mexico SSB tax was estimated to prevent 239,900 cases of obesity and 61,340 cases of T2D over 10 years, saving USD 3.98 for every dollar spent.
**Clinical Implications:** The evidence unequivocally shows that T2D can be prevented or delayed in high-risk individuals through lifestyle interventions, with sustained benefits for at least 5–10 years and up to 30 years. However, real-world implementation faces major challenges: low uptake (e.g., only 30% of referred individuals attended at least one session in the UK NHS DPP; 28% had 1-year follow-up data in FIN-D2D), variable reimbursement, and limited reach to disadvantaged populations. The authors emphasize that lifestyle interventions are effective across all ethnic groups and genetic risk levels, and that weight reduction is essential in overweight/obese individuals. They call for a global treaty for T2D prevention modeled on the WHO Framework Convention on Tobacco Control, incorporating multisectoral measures including taxation, subsidies for healthy foods, urban planning for physical activity, and coordinated national programs.