Background: Current guidelines recommend insulin alone for in-hospital management of diabetes, but growing information suggests that new oral or injectable agents may be as effective and safe. Methods: Systematic review and meta-analysis with evidence from randomized (RCT) and non-randomized (NRS) studies in PubMed, EMBASE and LILACS databases up to February 10, 2022, for studies including hospitalized type 2 diabetes patients, comparing dipeptidyl peptidase 4 inhibitors (DPP4i), sodium glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP1Ra) with insulin alone for glycemic control and safety outcomes. Findings: 7 RCT and 3 NRTs were included. There were no differences in mean blood glucose, measurements within range or rate of hypoglycemia between DPP4i and insulin. We found a lower mean glucose for GLP1Ra plus insulin subgroup (−16.36 mg/dL, 95 % CI −27.31, −5.41; I2 = 0 %) with lower incidence of hypoglycemia < 70 mg/dL with GLP1Ra (RR 0.31, CI 95 % 0.14–0.70, I2 = 0 %). SGLT2i data was limited. Adverse events rates were similar between treatments. Conclusion: Our review suggests that inpatient management in the general ward with DPP4i and GLP1Ra is as effective and safe as management with insulin. More randomized studies are required to support these findings before they could be recommended as usual practice.