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Metformin has been shown to reduce the accumulation of AGEs in the sciatic nerves of rats with streptozotocin (STZ)-induced diabetes by activating AMPK, leading to improved nerve conduction velocity, and the attenuation of heat and mechanical hyperalgesia (59)

The main risk is premature extrapolation from animal models to claims of an osteoarthritis cure

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There appears to be a dose effect for physical activity and weight loss, and much greater amounts of exercise are necessary to produce significant weight loss in the absence of a calorically restricted diet