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Lastly, a big difference can come in side effects. While both natural and prescription weight loss pills will come with their respective side effects, generally natural weight loss pills will be milder. This is due to the fact that prescription diet pills are a drug, and typically more concentrated. An astonishing 15 percent of U.S. adults have used a weight-loss dietary supplement at some point in their lives, and Americans spend about $2.1 billion a year on weight-loss dietary supplements