your LiveData can be referencing MutableLiveData, where you post stuff

private val userMLD = MutableLiveData<List<User>>()
val userLiveData: LiveData<List<User>> = userMLD

and

    private fun getUsers() {
        val apiHelper = ApiHelper(RetrofitBuilder.apiService)
        val mainRepository = MainRepository(apiHelper)
        userMLD.postValue(mainRepository.getUsers())
    }

Instead of creating a LiveData everytime, run your code inside a coroutine and update the LiveData with the new value. You need a MutableLiveData for that:

class MainActivity : AppCompatActivity() {
    
    private val userLiveData = MutableLiveData<List<User>>()

    override fun onCreate(savedInstanceState: Bundle?) {
        super.onCreate(savedInstanceState)
        setContentView(R.layout.activity_main)

        getUsers()     //WORKING <---------
        userLiveData.observe(this, Observer {
            it.forEach { user ->
                Log.i("TAG", user.name)
            }
        })

        lifecycleScope.launch {
            delay(5000)  //Refresh the result
            getUsers()   //NOT WORKING <---------
        }
    }

    private fun getUsers() {
        val apiHelper = ApiHelper(RetrofitBuilder.apiService)
        val mainRepository = MainRepository(apiHelper)
        lifecycleScope.launch {
            val users = withContext(Dispatchers.IO) {
                mainRepository.getUsers()  //Suspend function
            }
            
            userLiveData.value = users
        }
    }
}

The code below works only once.

class MainActivity : AppCompatActivity() {


    lateinit var userLiveData: LiveData<List<User>>

    override fun onCreate(savedInstanceState: Bundle?) {
        super.onCreate(savedInstanceState)
        setContentView(R.layout.activity_main)

        getUsers()     //WORKING <---------
        userLiveData.observe(this, Observer {
            it.forEach { user ->
                Log.i("TAG", user.name)
            }
        })

        lifecycleScope.launch {
            delay(5000)  //Refresh the result
            getUsers()   //NOT WORKING <---------
        }
    }

    private fun getUsers() {
        val apiHelper = ApiHelper(RetrofitBuilder.apiService)
        val mainRepository = MainRepository(apiHelper)
        userLiveData = liveData {
            val res = mainRepository.getUsers()  //Suspend function
            emit(res)
        }
    }
}

The first time I call the getUsers() function, I can see the logs. But Later I call getUsers() , there is no log on the screen.
Which means that the userLiveData.observe( function runs once.