OBJECTIVES: Diabetes is a serious, chronic disorder that has an enormous detrimental impact on people's lives, families, and society around the globe. Hence, new treatment options with better safety and efficacy are required. The aim of the study is to summarize the efficacy and safety of five novel anti-glycemic drug.

METHODS: The study examines ongoing clinical trials evaluating the efficacy and safety of drugs like Cotadutide, Enavogliflozin, Retatrutide, ORMD-0801, and Imeglimin for T2DM, and reported data for at least 1 outcome of interest. All major databases, like PubMed, Google Scholar, and the Cochrane Central Register of Controlled Trials (CENTRAL), as well as conference abstracts published in journals supplementary issues and ClinicalTrials.gov, were searched until July 15, 2023.

RESULTS: New anti-glycemic drugs have been found to be effective and well-tolerated for treating T2DM. ORMD-0801, an encapsulated human insulin, was found to be safe and effective in treating T2DM patients with inadequate glycemic control, with minimal impact on liver function and triglyceride levels. Retatrutide treatment significantly reduced plasma glucose levels and body weight, with the highest dose group achieving a maximum reduction of weight up to 24.2%, with gastrointestinal disorders being common adverse events. Cotadutide, an insulinotropic drug, has shown promising results in improving glycemic control and weight loss in T2DM patients through delayed gastric emptying. Enavogliflozin had a slightly larger reduction in HbA1c levels (-0.99%) than Bexagliflozin. Imeglimin, at 1000 mg BID, significantly lowers HbA1C levels to -0.72%. As monotherapy or adjunctive therapy (with metformin), it is found to be effective, has low risk of hypoglycemia, and enhances insulin action and sensitivity.

CONCLUSIONS: Over the past decade, numerous glucose-lowering medications have been approved, requiring careful consideration of their risks and benefits. It is critical to establish the strongest evidence for improving glycemic control and reducing the risk of complications.