Efficacy and safety of the combination or monotherapy with GLP-1 receptor agonists and SGLT-2 inhibitors in Type 2 diabetes mellitus: An update systematic review and meta-analysis

Purpose To evaluate the efficacy and safety of combination therapy with sodium-glucose cotransporter2(SGLT-2) inhibitors and glucagon-like peptide-1(GLP-1) receptor agonists in the treatment of type 2 diabetes mellitus (T2DM). Methods To construct an exhaustive database of randomized controlled trials (RCTs) concerning SGLT-2 inhibitors and GLP-1 agonists, a methodical search was undertaken across a range of databases, such as Embase, PubMed, and the Cochrane Central Register of Controlled Trials, from their inception to January 2023. Following this, a meta-analysis was executed to amalgamate the collected data, which allowed for the calculation of standardized mean differences (SMDs), odds ratios (ORs), and 95% confidence intervals (CIs) for a spectrum of outcomes. This analytical approach was designed to yield a quantitative evaluation of the therapeutic efficacy and safety profile of SGLT-2 inhibitors and GLP-1 agonists for the treatment of diabetes mellitus. Results When compared to GLP-1 agonist therapy alone, the combination therapy did not significantly reduce fasting plasma glucose (FPG) levels (95% confidence interval [CI]: -0.27, 0.10; p=0.35), body weight (95% CI: -0.18, 0.18; p=1.00), Glycosylated Hemoglobin, Type A1C (HbA1c) (95% CI: -0.29, 0.07; p=0.22), or systolic blood pressure (SBP) values (95% CI: -0.29, 0.06; p=0.21). In contrast, when compared to SGLT-2 inhibitor therapy alone, combination therapy significantly decreased FPG by 0.24 mmol/L (95% CI: -0.43, -0.05; p=0.01), HbA1c by 0.45% (95% CI: -0.72, -0.18; p=0.001), and SBP by 0.12 mmHg (95% CI: -0.24, 0.00; p=0.05). However, the combination therapy failed to demonstrate a significant reduction in body weight when compared with either SGLT-2 inhibitor therapy (95% CI: -0.20, 0.05; p=0.24) or GLP-1 agonist therapy (95% CI: -0.18, 0.18; p=1.00). Additionally, the combination therapy did not increase the incidence of hypoglycemia. It should be noted that data regarding mortality and cardiovascular outcomes were limited. Conclusions The combination treatment of SGLT-2 inhibitors and GLP-1 receptor agonists effectively reduces HbA1c, FPG, and SBP without elevating the risk of hypoglycemia when compared to monotherapy with SGLT-2 inhibitors. However, these beneficial effects were not observed when the combination therapy was compared with GLP-1 receptor agonist treatment alone.