Comparative efficacy and safety profile of once-weekly Semaglutide versus once-daily Sitagliptin as an add-on to metformin in patients with type 2 diabetes: a systematic review and meta-analysis

BACKGROUND: The emergence of genetically-modified human proteins and glucagon-like peptide-1 (GLP-1) receptor agonists have presented a promising strategy for effectively managing diabetes. Due to the scarcity of clinical trials focusing on the safety and efficacy of semaglutide as an adjunctive treatment for patients with type 2 diabetes who had inadequate glycemic control with metformin, we conducted a systematic review and meta-analysis. This was necessary to fill the gap and provide a comprehensive assessment of semaglutide compared to sitagliptin, a commonly prescribed DPP-4 inhibitor, in this patient population. METHODS: A comprehensive and systematic search was carried out on reputable databases including PubMed, the Cochrane Library, and Elsevier's ScienceDirect to identify relevant studies that compared the efficacy of once-weekly Semaglutide with once-daily Sitagliptin in individuals diagnosed with type 2 diabetes mellitus. The analysis of the gathered data was performed utilizing the random-effects model, which considers both within-study and between-study variations. RESULTS: The meta-analysis incorporated three randomized controlled trials (RCTs), encompassing 2401 participants, with a balanced distribution across the treatment groups. The primary focus of the study revolved around evaluating changes in HbA1C, blood pressure, pulse rate, body weight, waist circumference, and BMI. The findings revealed that once-weekly Semaglutide showed substantially improved HbA1C (WMD: -0.98; 95% CI: -1.28, -0.69, p-value: < 0.0001; I2: 100%), systolic (WMD: -3.73; 95% CI: -5.42, -2.04, p-value: <0.0001; I2: 100%) and diastolic blood pressures (WMD: -0.66; 95% CI: -1.02, -0.29, p-value: 0.0005; I2: 100%), and body weight (WMD: -3.17; 95% CI: -3.84, -2.49, p-value: <0.00001; I2: 100%) compared to once-daily Sitagliptin. However, there was an observed increase in pulse rate (WMD: 3.33; 95% CI: 1.61, 5.06, p-value: <0.00001; I2: 100%) associated with Semaglutide treatment. Regarding secondary outcomes, there was an elevated risk of total adverse events and premature treatment discontinuation with Semaglutide. The risk of serious, severe, moderate, and mild adverse events did not significantly differ between the two treatments. CONCLUSIONS: In conclusion, the administration of once-weekly Semaglutide exhibited a substantial reduction in HbA1c, average systolic blood pressure (SBP), mean diastolic blood pressure (DBP), body weight, waist circumference, body mass index (BMI), and a rise in pulse rate, as opposed to the once-daily administration of Sitagliptin.