Harness the Polypill Concept for a Broader Set of Indications
(or preventive use)

“Combining renin-angiotensin system blockade and sodium-glucose cotransporter-2 inhibition in experimental diabetes results in synergistic beneficial effects”

https://pubmed.ncbi.nlm.nih.gov/38088400/

I’ve seen interesting advocacy for use of a polypill in cardiovascular disease, even heart failure with reduced ejection fraction; usually 3 or 4 meds including a choice of beta-blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, all in low effective doses. Generally such combinations are reported well-tolerated.

E.g., “Polypill Strategy for Heart Failure With Reduced Ejection Fraction”

https://ctv.veeva.com/study/polypill-strategy-for-heart-failure-with-reduced-ejection-fraction

Omitting the beta-blocker and mineralocorticoid receptor antagonists as unneeded except in heart failure cases, consider a polypill based on a sodium-glucose cotransporter-2 inhibitor and an angiotensin receptor blocker. Both these med classes are in wide use, well tolerated, and effective in their usual indications. Underlying their canonical mechanisms, benefits for mitochondrial function appear involved, most simply through SGLT2i inducing mild ketosis and ARB leading to AMPK activation or other effects on mitochondrial dynamics (also below). Prevalant conditions that may benefit from this approach include DM II including the risk of cardiovascular and renal complications, MASH and related liver fibrosis, other cardiovascular and renal diseases.

I’d wager that optionally adding in acarbose, another generally safe and well-tolerated med, separately administered with 1-2 meals a day, would result in a gentle weight loss. The acarbose intestinal glucosidase inhibition would be independent of the SGLT2i glycosuria effect, but compatible and complementary to further lower glucose availability in circulation, prompting compensatory lipolysis and liver gluconeogenesis and so gradually decreasing the adipose burden in patients who may need this.

Modulation of Mitochondrial Dynamics by the Angiotensin System in Dopaminergic Neurons and Microglia

https://www.aginganddisease.org/EN/10.14336/AD.2024.0981

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