How to disable multiple thumbnail generation?

You can disable the medium and large image sizes by using the ‘intermediate_image_sizes’ filter:

function remove_image_sizes($image_sizes){
    foreach($image_sizes as $key => $size){
        if($size == 'large' || $size == 'medium')
            unset($image_sizes[$key]);
    }
    return $image_sizes;
}
add_filter('intermediate_image_sizes', 'remove_image_sizes', 12, 1);

This skips adding these sizes and the options to insert a medium/large image are left blank in the media item.