BACKGROUND: Insulin has recently received special attention concerning its use in COVID-19 patients. Although controversial, insulin can be able to worsen the prognosis of COVID-19 patients with Type 2 Diabetes Mellitus (T2DM) through an inflammatory pathway. This uncertain aspect brings a new perspective related to insulin use in this pandemic era. OBJECTIVE: We tried to collect and analyze various studies related to this issue to provide a complete picture of the prognosis of insulin use in COVID-19 patients with T2DM. METHODS: We comprehensively searched PubMed, Cochrane CENTRAL, Embase, EBSCO CINAHL, MEDLINE, and grey literature databases for studies investigating the effect of insulin on COVID-19 outcomes, including mortality, hospitalization, disease progression, other prognostic surrogates. Records were screened against the eligibility criteria. RESULTS: 2556 articles were retrieved and were screened. A total of 8 studies were included in the final analysis. There are no studies with solid evidence supporting the effect of insulin treatment on the worsening of the prognosis of COVID-19 patients with T2DM. Although several studies have shown that insulin is associated with a poor prognosis, most studies have not considered confounders. This certainly makes it challenging to analyze the effects of insulin independently. CONCLUSION: We propose that COVID-19 patients with T2DM continue to receive insulin, but with careful observation of the risk of disease progression.