Glycaemic Control, Obesity Management, and Cardiovascular Outcomes of Semaglutide for Type 2 Diabetes Mellitus Patients: An Umbrella Review of Meta-Analyses of Randomized Clinical Trials

OBJECTIVES: To conduct an umbrella review of meta-analyses evaluating glycaemic control, obesity management, and cardiovascular outcomes associated with semaglutide in type 2 diabetes mellitus (T2DM) patients.

METHODS: A systematic search was conducted in PubMed, Europe PMC, Epistemonikos, and Google Scholar from database inception till June 2024. The inclusion criteria were: (1) meta-analyses of randomised controlled trials (RCTs) that compared oral semaglutide (7mg, 14mg) or subcutaneous semaglutide (0.5mg, 1.0mg) with placebo in adults with T2DM and (2) studies assessing change in HbA1c %, fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP). The exclusion criteria were: (1) mixed or paediatric populations and (2) studies assessing single trials for semaglutide. The methodological quality of each included meta-analysis was assessed using the Assessment of Multiple Systematic Reviews-2 (AMSTAR 2) checklist.

RESULTS: Eleven meta-analyses were included. All the studies reported data on glycaemic control, ten reported obesity, and six reported cardiovascular outcomes. Findings demonstrate a notable reduction in HbA1c levels with semaglutide (comparable reduction for all doses and routes of administration) compared to placebo. Subcutaneous semaglutide 1mg showed greatest reduction in FPG (-2.00 to -2.52 mmol/L) compared to placebo, followed by subcutaneous semaglutide 0.5mg (-1.34 to -2.02 mmol/L) and oral semaglutide 14mg (-1.65 to -1.72 mmol/L). Subcutaneous semaglutide 1mg showed greatest reduction in body weight (-3.83 to -4.39 kg) compared to placebo, followed by oral semaglutide 14mg (-2.89 to -3.47 kg) and subcutaneous semaglutide 0.5mg (-2.06 to -2.83 kg). Compared to placebo, semaglutide showed a higher reduction in SBP (subcutaneous 1mg [-3.05 to -6.28 mmHg], oral 14mg [-2.33 to -3.58 mmHg], subcutaneous 0.5mg [-1.31 to -5.41 mmHg]). Changes in DBP with semaglutide were comparable to those with placebo.

CONCLUSIONS: This umbrella review found a beneficial association of semaglutide with glycaemic control, obesity management, and cardiovascular outcomes compared to placebo in T2DM patients.