Should you treat prediabetes? It’s complicated
While treatment with metformin or lifestyle modification reduces risk for T2D in patients with prediabetes, neither intervention ultimately offers a mortality benefit.
PRACTICE CHANGER
STRENGTH OF RECOMMENDATION
B: Based on a long-term follow-up of a randomized controlled trial.1
Lee CG, Heckman-Stoddard B, Dabelea D, et al; Diabetes Prevention Program Research Group. Effect of metformin and lifestyle interventions on mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study. Diabetes Care. 2021;44:2775-2782. doi: 10.2337/dc21-1046
CAVEATS
Exclusion criteria, residual confounding may limit the findings
Patients with significant cardiovascular or renal disease were excluded, so results may not apply to patients with these comorbidities. Additionally, there was a high amount of “drop-in” use of metformin prescribed by physicians once patients developed T2D, which may not have been controlled for completely. And while the intensive lifestyle intervention group had specific goals, the metformin and placebo groups also were encouraged to follow standard diet and lifestyle recommendations—and during a bridge period, all participants were offered a modified group lifestyle intervention. However, multivariable adjustment did not change the study conclusion.
CHALLENGES TO IMPLEMENTATION
Physicians may be unwilling to change their current prescribing habits
Physicians may not be willing to change their practice of prescribing metformin in prediabetes based on a singular study (with residual confounding) that showed no long-term mortality differences between the study groups. However, there may be long-term morbidity differences of interest to patients that were not specifically evaluated in this study—such as quality-of-life benefits from weight loss that may outweigh the risks (eg, gastrointestinal adverse effects such as diarrhea, nausea, and abdominal pain) of metformin for some patients. Therefore, a discussion of the risks and benefits of treatment for prediabetes should be had with patients at high risk who would prefer a pharmacologic intervention.
