Empagliflozin Extends Lifespan While Reducing Physical Activity in Drosophila Melanogaster: Insights into Non-Glycemic Pharmacological Effects

Le résumé fourni par la source

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), such as empagliflozin (EMPA), are primarily used to manage hyperglycemia in type 2 diabetes (T2D). Beyond their role in glycemic control, SGLT2i can elicit off-target effects, including induction of a mild energetic stress phenotype—a state previously associated with increased longevity in various organisms. Drosophila melanogaster lack the SGLT2 protein and, therefore, can be used to model the effects of SGLT2i independent of renal glucose reuptake. We tested the hypothesis that EMPA would promote and increase longevity and physical activity (PA) by providing adult virgin female Drosophila with either DMSO (vehicle) or EMPA in the diet at concentrations of 5 μM, 25 μM, and 50 μM. EMPA treatment resulted in a significant extension of median lifespan at all concentrations: 4% (p=0.049) for 5 μM, 24% (p=0.035) for 25 μM, and 8% (p=0.025) for 50 μM, compared with DMSO. A linear mixed model analysis also demonstrated significant interactions between EMPA treatment and time on PA levels—5 μM (p=0.001), 25 μM (p=0.04), and 50 μM (p=5.85e-07)—indicating a pronounced reduction in PA over time in EMPA-treated groups compared with DMSO. Our findings that EMPA promotes longevity and lowers physical activity in Drosophila demonstrate that SGLT2i can have significant physiologic impacts that are independent of inhibition of SGLT2. Supported by funding from the Valley Fellowship (Oregon State University) awarded to SAN. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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