While it's still not possible to force the configuration of a 2FA at the user level without the Devolutions Server , a few options have been added in Remote Desktop Manager that could suit your needs.
These features are only available when using an Advanced Data Source
You cannot configure 2FA for users. Once activated, each user will need to configure it manually in File - DataSources For more information about configuration consult this topic: 2-Factor Authentication
Force application security with Windows credentials
Under Administration - System Settings - Applications - Security - Force application security with Windows credentials
Force application security with TOTP (Authenticator)
Under Administration - System Settings - Applications - Security - Force application security with TOTP (Authenticator)
Force data source 2-factor configuration
Under Administration - System Settings - Security Settings - Security - Force data source 2-factor configuration
Force with Group Policies (GPO)
We also have GPOs that could help you achieve your goal. An example in this case is the Force multiple-factor authentication on the application login
%Root%\SOFTWARE\Policies\Devolutions\RemoteDesktopManager\ForceApplicationMFA
For more information about configuration, consult this topic How to Apply Policies