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Weight loss drugs or anti-obesity drugs have a long history but are still far from being successful. Only in two last decades have the drugs been launched, which, when appropriately indicated, may be significantly beneficial to patients in need of weight loss as they are comparably effective to intensive programs to promote changes in eating habits and lifestyles. The combination naltrexone/bupropion is promising for food intake control including the reward mechanism, but the experience with its use has only been short-term. The lipase inhibitor orlistat remains the safest therapeutic option. The already restricted use of phentermine, newly classified as a controlled opiate substance, has become practically blocked. The range of weight loss drugs can be extended with some antidiabetics, particularly liraglutide and gliflozins. A number of other substances is still in the research stage.