RESEARKA

The human RCT landscape for metformin effects now extends well beyond glycemic endpoints, though the evidence base remains heterogeneous in design, population, and outcome selection. Metformin effects on cardiometabolic outcomes have been examined in systematic reviews and meta-analyses of trials enrolling predominantly white, overweight adults aged 65 years or younger with poor glycemic control (Griffin 2017), limiting generalizability to older or more diverse populations. In prediabetes, a Bayesian network meta-analysis has evaluated multiple anti-prediabetic drugs including metformin, though effect estimates remain imprecise (Wu 2026). Functional-endpoint trials are now emerging, including a proof-of-concept RCT assessing metformin effects on physical performance in older adults with sarcopenia and prefrailty (Rennie 2022), and a planned study in polycystic ovary syndrome targeting metabolic and reproductive outcomes (Hautamaki 2026). The diversity of ongoing trials is encouraging, yet the predominance of surrogate rather than hard clinical endpoints means that the clinical significance of metformin effects on aging remains uncertain.

Citation Support

• source_1 Zaveri 2026
• source_2 Wu 2026
• source_3 Hong 2026
• source_4 Lee 2026
• source_5 Seo 2026