Highlights
– A stepped-care prevention program with financial incentives reduced 3‑year diabetes incidence from 47.3% to 34.8% in overweight/obese adults with prediabetes (adjusted RR 0.74; P < 0.001).
– The intervention combined an initial 6‑month lifestyle program, selective addition of metformin for persistent high-risk participants (26.4% received metformin), and cash rewards for attendance and ≥5% weight loss (45.1% received incentives).
– Adverse events were more frequent in the intervention arm, mainly metformin-related gastrointestinal symptoms; long‑term durability and cost‑effectiveness remain to be established.
Background: The clinical need
Type 2 diabetes mellitus is a leading cause of morbidity worldwide, with disproportionately high incidence and complications in many Asian populations at lower body‑mass index (BMI) thresholds than in Western populations. Prediabetes—defined by impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or elevated glycated hemoglobin—is a high‑risk state for progression to type 2 diabetes. Landmark randomized trials have shown that structured lifestyle modification can markedly reduce progression to diabetes, and metformin provides additional benefit in selected individuals. Translating these findings into routine care faces two major barriers: limited sustained patient adherence to behavior change programs and challenges of delivering scalable, cost‑effective interventions in real‑world health systems.
Study design: The Pre‑DICTED randomized controlled trial
Pre‑Diabetes Interventions and Continued Tracking to Ease Out Diabetes (Pre‑DICTED) was a randomized controlled trial enrolling 751 overweight or obese adults with prediabetes (IFG, IGT, or both) in Singapore. Participants were randomized to standard care (control) or a stepped‑care intervention program. The core components of the intervention were:
- An initial 6‑month structured lifestyle intervention focused on diet, physical activity, and weight loss
- Step‑up treatment with metformin for participants who remained at high risk of diabetes conversion after the lifestyle phase, based on study visit assessments
- Financial incentives (cash payments) for attending lifestyle sessions and for achieving ≥5% weight loss during the program
The primary outcome was the proportion of participants who developed diabetes at 3 years in the modified intention‑to‑treat population. Secondary outcomes included uptake of metformin, proportion receiving incentives, weight change, and adverse events. The trial population was multiethnic Asian, reflecting Singapore’s demographics.
Key findings
Primary outcome
At 3 years, 34.8% of participants in the intervention arm developed diabetes compared with 47.3% in the control arm. The adjusted risk difference was −10.93% (95% CI −18.04 to −3.81; P = 0.003). The adjusted relative risk was 0.74 (95% CI 0.62–0.88; P < 0.001). Using the adjusted absolute risk reduction (≈11%), the number needed to treat (NNT) to prevent one case of diabetes over 3 years is approximately 9 (1/0.1093 ≈ 9.2).
Intervention uptake and intermediate outcomes
Within the intervention arm, 26.4% of participants received metformin during follow‑up, reflecting the stepped‑care strategy that reserved pharmacotherapy for persistent high‑risk individuals. Nearly half (45.1%) of intervention participants received cash incentives for attendance and/or achieving ≥5% weight loss, indicating moderate engagement with the incentive structure. The report highlights that the incentives were targeted both to program participation and to clinically meaningful weight loss, a key mediator of diabetes risk reduction.
Safety
Adverse events were reported more commonly in the intervention arm, primarily because of gastrointestinal symptoms attributed to metformin. No unexpected safety signals were described. The increased rate of mild to moderate GI adverse events is consistent with metformin’s known tolerability profile; however, the trial underscores the importance of monitoring and counseling when metformin is used in prevention programs.
Statistical and clinical interpretation
The observed relative risk reduction (~26%) and an absolute reduction of roughly 11–12% at 3 years are clinically meaningful in a high‑risk cohort. The magnitude of effect compares favorably with prior randomized prevention studies in which intensive lifestyle programs and/or metformin reduced diabetes incidence. Importantly, this trial operationalized a pragmatic stepped‑care model and added behavioral economics elements (cash incentives), demonstrating effectiveness in a real‑world, multiethnic Asian population rather than a tightly controlled research setting.
Expert commentary: strengths, limitations, and place in practice
Strengths
The study’s principal strengths include randomized design, a sizable sample, pragmatic stepped‑care delivery, focus on a multiethnic Asian population (an understudied group that faces unique risk profiles), and incorporation of incentives to address adherence—an acknowledged barrier in diabetes prevention. Reporting of adjusted effect estimates with confidence intervals supports the robustness of findings.
Limitations and cautions
Several issues merit consideration when translating these findings into practice:
- Modified intention‑to‑treat analysis: The specific reasons for modification should be inspected in the primary report to assess potential bias from missing data or exclusions.
- Generalisability: The trial was conducted in Singapore with a particular healthcare infrastructure and social context; effectiveness, acceptability, and cost‑effectiveness of cash incentives may differ in other health systems and cultural settings.
- Uptake of metformin was modest (26.4%), so the net effect depended primarily on the lifestyle program and incentives rather than broad pharmacologic prophylaxis. The adherence and fidelity of lifestyle delivery in routine practice influence real‑world impact.
- Short‑ to medium‑term follow‑up: Three years is informative, but diabetes prevention strategies ideally require longer follow‑up to assess durability of benefit and whether early prevention reduces long‑term complications.
- Cost and equity implications: Financial incentives may improve uptake but raise questions about sustainability, cost‑effectiveness, and whether incentives preferentially benefit or disadvantage subgroups. Economic analyses are necessary before scale‑up.
How this aligns with current evidence and guidelines
Clinical guidelines endorse intensive lifestyle intervention as the foundation of diabetes prevention, with metformin as a consideration for high‑risk individuals—particularly younger, more obese, or those with prior gestational diabetes. The Pre‑DICTED trial provides contemporary, population‑specific evidence that a scalable, stepped‑care approach combining behavioral programs, selective metformin use, and incentives can produce significant risk reductions consistent with earlier foundational trials (e.g., the Diabetes Prevention Program and Finnish Diabetes Prevention Study).
Mechanistic rationale
Weight loss achieved through diet and activity reduces insulin resistance and decreases hepatic glucose production, key pathophysiologic mechanisms in progression from prediabetes to diabetes. Metformin primarily reduces hepatic gluconeogenesis and improves peripheral insulin sensitivity, complementing lifestyle interventions. Financial incentives operate via behavioral economic mechanisms—increasing immediate rewards for healthy behaviors to overcome temporal discounting and improve short‑term adherence, which may allow establishment of durable habits.
Implications for clinicians and policymakers
For clinicians: The Pre‑DICTED data support offering structured lifestyle programs to patients with prediabetes and considering a stepped approach that reserves metformin for individuals who remain at high risk after an initial lifestyle phase. Discuss expected benefits (roughly one case of diabetes prevented per 9 treated over 3 years based on adjusted estimates) and potential metformin side effects.
For health systems and policymakers: Cash‑based incentives improved engagement and may enhance effectiveness of prevention programs, but decisions to implement such incentives should weigh costs, equity, feasibility, and public acceptability. Implementation pilots with embedded process and economic evaluations are appropriate next steps before widespread adoption.
Conclusion
The Pre‑DICTED randomized trial demonstrates that a stepped‑care diabetes prevention program augmented by financial incentives lowered 3‑year diabetes incidence in a multiethnic Asian prediabetes cohort. The pragmatic design, targeted use of metformin, and incorporation of behavioral incentives make the intervention a promising model for real‑world prevention strategies. Key uncertainties include long‑term durability, cost‑effectiveness, and generalisability across diverse health systems. Future work should include economic evaluation, subgroup analyses to identify populations most likely to benefit, and longer follow‑up to evaluate the persistence of effect and impact on diabetes‑related complications.
Funding and clinicaltrials.gov
Funding and trial registration details are reported in the primary publication: Bee YM et al., Diabetes Care 2025. Readers should consult the original article for full disclosures, funding sources, and registry identifiers.
References
1. Bee YM, Awasthi N, Gandhi M, et al. Effectiveness of an Incentives‑Enhanced Stepped Care Intervention Program in Diabetes Prevention in a Multiethnic Asian Prediabetes Cohort: Results From the Pre‑DICTED Randomized Controlled Trial. Diabetes Care. 2025 Nov 1;48(11):1951‑1959. doi: 10.2337/dc25‑1555. PMID: 40970814; PMCID: PMC12583383.
2. Knowler WC, Barrett‑Connor E, Fowler SE, et al.; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393‑403. doi:10.1056/NEJMoa012512.
3. Tuomilehto J, Lindström J, Eriksson JG, et al.; Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001 May 3;344(18):1343‑50. doi:10.1056/NEJM200105033441801.
4. American Diabetes Association. 6. Prevention or Delay of Type 2 Diabetes: Standards of Care in Diabetes—2024. Diabetes Care. 2024;47(Suppl 1):S153‑S161. (Guideline summary for prevention strategies including lifestyle and metformin.)
