(1101) Safety and Effectiveness of Sodium-glucose cotransporter-2 Inhibitors in Comparison with Glucagon-like peptide-1 Agonists on Weight Loss: A Meta-analysis

Objectives: Obesity has emerged as a pervasive and multifaceted public health challenge in the United States. In the battle against the global obesity epidemic, medications initially designed for diabetes management, sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, appear as potential agents for weight loss. The purpose of this meta-analysis is to review the existing literature to compare SGLT-2 inhibitors or GLP-1 receptor agonists' effectiveness in terms of weight loss and safety profile of cardiac, gastrointestinal, and renal serious adverse drug reactions (ADR).

Methods: A literature search was conducted through PubMed, EMBASE, and Cochrane Library. The keywords “SGLT-2 inhibitors” and “obesity” or “GLP-1 receptor agonists” and “obesity” were used to identify research that referenced completed clinical trials. To conduct the ADR literature search, the terms “SGLT-2 inhibitors” and “safety” or “GLP-1 receptor agonists” and “safety” were used. The inclusion criteria consisted of completed clinical trials of SGLT-2 inhibitors and GLP-1 receptor agonists containing a treatment group and a placebo group. A total of 8 clinical trials reporting serious adverse events were evaluated in the following categories: cardiac, renal and gastrointestinal. This resulted in a total of 5,589 participants in the GLP-1 receptor agonist clinical trials and 5,969 participants in the SGLT-2 inhibitor clinical trials. Additional research referencing the same underlying clinical trial was redundant and excluded. Each article was reviewed by a second reviewer simultaneously and independently. A statistical analysis was performed using Review Manager 5.4, R Studio, R version 4.3.1 and Microsoft® Excel® for Microsoft 365 MSO (Version 2308 Build 16.0.16731.20182) 32-bit.

Results: A thorough statistical analysis was performed, Z-tests and p-values were used to determine if the data was statistically significant for weight loss. Safety data was evaluated for each drug class in terms of relative risk ratios, as shown in Figure 3. The GLP-1 receptor agonists produced a Z-value of 6.17 (p < 0.00001), as shown in Figure 1. The analysis of the SGLT-2 inhibitors produced a Z-value of 8.58 (p < 0.00001), as shown in Figure 2. Both results are statistically significant with a confidence interval greater than 99%.Therefore, this indicates that both drugs are capable of producing weight loss when combined with lifestyle modifications. However, the weight loss that was attained with the GLP-1 receptor agonist treatment -4.68 [-6.64, -2.73] was 3.23 times that of the SGLT-2 inhibitor -1.45 [-1.89, -1.02]. Further, it was found that GLP-1 receptor agonists were 5.87% and 40.79% safer in terms of cardiac and GI events, respectively. Conversely, the SGLT-2 inhibitors are 12.45% safer regarding renal serious ADR. It is important to consider that randomized controlled trials investigating the effectiveness and safety of diabetes medications for the use of weight loss in healthy populations are scarce. Therefore, a significant number of patients included in the clinical trials analyzed in this meta-analysis were individuals who may have been diabetic and/or obese. The prevalence of chronic comorbidities are common in individuals with a BMI greater than 27.0 (kg/m2). More studies need to be conducted on healthy individuals without pre-existing conditions.

Conclusions: This meta-analysis highlights significant weight loss benefits with GLP-1 receptor agonists and SGLT-2 inhibitors for obesity treatment. Although GLP-1 receptor agonists excel in weight loss, clinicians must consider the presence of underlying medical conditions that may be exacerbated when evaluating treatment. SGLT-2 inhibitors exhibit better safety profiles for renal issues. However, GLP-1 receptor agonists excel in gastrointestinal safety profiles. Medication assisted weight loss combined with diet and exercise can help maintain a healthy weight post-treatment, while the overall risk of adverse drug reactions with either class remains low.