Researchers at Healthspan Medical unveiled how SGLT-2 inhibitors, originally developed to lower blood sugar, emulate the metabolic effects of caloric restriction by promoting urinary glucose excretion. This mild energy deficit activates longevity pathways—AMPK, SIRT1—while suppressing mTOR and insulin/IGF-1 signaling, thereby enhancing autophagy, mitochondrial function, and metabolic flexibility. The pharmacological approach offers a practical alternative to strict dietary interventions for promoting healthier cellular aging.

Key points

• SGLT-2 inhibitors induce mild glucosuria (~60–80 g/day), mimicking a continuous fasting state
• Activated AMPK and SIRT1 pathways enhance fatty acid oxidation, mitochondrial biogenesis, and cellular repair
• Inhibited mTOR and reduced insulin/IGF-1 signaling promote autophagy and reduce pro-growth signaling
• Empagliflozin demonstrated reduced hepatic steatosis, lowered pro-inflammatory M1 macrophages, and increased UCP1 expression in HFD-fed mice
• Early human data show weight loss, improved insulin sensitivity, and cardiometabolic risk-factor reduction

Why it matters: By replicating the cellular effects of caloric restriction without severe dietary changes, SGLT-2 inhibitors may shift the aging paradigm toward pharmacological metabolic reprogramming. This approach could provide a scalable therapy to enhance healthspan, mitigate age-related diseases, and overcome adherence barriers associated with traditional fasting or caloric restriction regimens.