Early intensive lifestyle intervention (ILS) is most effective in delaying diabetes progression among those with higher baseline HbA1c, whereas metformin treatment effects tend to be greatest among younger patients than older patients, according to study findings published in The Lancet.
In studies involving adults at high risk for type 2 diabetes (T2D), evidence supports that behavioral and pharmacological interventions delay or prevent the onset of diabetes for several years. However, data on their long-term effectiveness remain limited.
To examine the potential heterogeneity and long-term effects of treatment over a follow-up period of 21 years between July 1996 and February 2020, researchers conducted the randomized controlled US Diabetes Prevention Program (DPP; ClinicalTrials.gov Identifier: NCT00004992) and DPP Outcomes Study (DPPOS; ClinicalTrials.gov Identifier: NCT00038727) trials.
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The relative benefits of ILS and drug interventions might change with future research on newer medicines, including GLP-1RAs, that reduce hyperglycemia and body weight, and with improvements in the long-term maintenance of behavioral weight loss.
The researchers randomly assigned the participants to 1 of 3 groups: placebo, metformin, or ILS. After unmasking, the researchers discontinued the placebo, continued metformin (850 mg twice daily as tolerated), offered booster lifestyle classes twice a year to the ILS group, and provided all participants with group-based lifestyle sessions 4 times a year. For all participants in the study population, the researchers employed a doubly homogeneous Poisson model to calculate the rate difference (RD) and the respective confidence intervals.
The primary outcome was diabetes incidence, defined as semiannual fasting plasma glucose of 126 mg/dL or higher (≥7.0 mmol/L) or 2-h plasma glucose of 200 mg/dL or higher (≥11.1 mmol/L) in an annual 75 g oral glucose tolerance test.
The study included 3195 participants, comprising 1024 (32.1%) men and 2171 (67.9%) women with a mean (SD) baseline age of 50.6 (10.7) years.
During the follow-up period, ILS and metformin vs placebo significantly lowered diabetes incidence, with notable gains in diabetes-free survival.
Relative to placebo, the ILS group had:
- 24% reduction in diabetes risk (hazard ratio [HR], 0.76; 95% CI, 0.68-0.85);
- 1.59 fewer cases per 100 person-years (RD, -1.59; 95% CI, -2.25 to -0.93); and,
- Median and mean diabetes-free survival increases of 3.5 years and 2.0 years, respectively.
On the other hand, the metformin group vs placebo had:
- 17% reduction in diabetes risk (HR, 0.83; 95% CI, 0.74-0.93);
- 1.17 fewer cases per 100 person-years (RD, -1.17; 95% CI, -1.85 to -0.49); and,
- Median and mean diabetes-free survival increases of 2.5 years and 1.2 years, respectively.
On the HR scale, ILS effects were generally homogeneous but greater among those with greater vs lower baseline HbA1c, whereas metformin effects were homogeneous. On the RD scale, ILS effects were greater among highest risk baseline fasting glucose and HbA1c subgroups, whereas metformin effects were greater among younger vs older patients.
Study limitations include limited generalizability due to rigorous diabetes assessment and specific eligibility criteria, reduced interpretability from changing intervention adherence over time, imprecise subgroup analyses due to small sizes, and inability to conduct direct comparisons with newer treatments such as glucagon-like peptide-1 receptor agonists (GLP-1RAs).
The authors concluded, “The relative benefits of ILS and drug interventions might change with future research on newer medicines, including GLP-1RAs, that reduce hyperglycemia and body weight, and with improvements in the long-term maintenance of behavioral weight loss.”