Behavioral intervention
Exercise
Aerobic and resistance training. Improves mitochondrial density and function, insulin sensitivity, VO2 max, lean mass retention, and vascular function. Acts on multiple hallmarks simultaneously rather than a single pathway.
Last reviewed 2026-10-22
What the evidence shows
Exercise carries a stronger human outcome base than any graded supplement in this registry — decades of randomized trials and large cohorts with hard endpoints including all-cause mortality, cardiovascular events, and fracture. It scores below the top band not on evidence volume but on blinding: exercise trials cannot be placebo-controlled, which caps Signal Source Quality, and dose-response across modalities is still imprecise.
What was actually studied
Trial protocols cluster around 150 min/week moderate aerobic activity plus 2 sessions/week resistance training. Resistance training specifically is the evidenced countermeasure to lean-mass loss on GLP-1 therapy.
Cautions and limitations
Cardiac screening advised before vigorous programs in sedentary adults over 40 or anyone with known cardiovascular disease. Progression rate, not exercise itself, drives most musculoskeletal injury.
Systems affected
Documented combinations
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Metformin
— Antagonistic
Metformin blunts exercise-induced adaptation
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Semaglutide
— Synergistic
Mandatory combination
Resistance training is the countermeasure to GLP-1 lean-mass loss
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Berberine
— Conditional
Berberine inherits the metformin AMPK caution