1664-P: An Observation of an Increase in the Metabolic Syndrome Parameters after Stopping GLP-1RA Medications in STEP-4 and SURMOUNT-4 Trials

Introduction and Objective: GLP-1 RA (Receptor Agonist) medications are commonly used by overweight and obese individuals for weight reduction, however, there is still a question about the metabolic consequences of stopping these agents. Methodology: Exploring the metabolic parameters in those who switched to placebo in two large clinical trials (STEP-4 and SURMOUNT-4). Results: In SURMOUNT-4 trial, after one year of stopping Tarazepide; there was an increase of metabolic syndrome parameters in the switched placebo group as follows; an increase in waist circumference by a mean of 8.3cm(7.4to9.2), raised in HbA1c by 0.25%(0.22to0.28), an increase of fasting blood sugar by 7.7mg/dl(6.6to8.8), systolic BP by 8.4mmHg(7.2to9.7), and an increase of triglyceride by 15.6%(10.9to 20).In the STEP-4 trial, stopping semaglutide for 48 months, there were similar adverse effects on metabolic syndrome parameters in the switched placebo group. The waist circumference increased by 3.0cm(2.1to4.0), fasting blood sugar increased by 7.1mg(6.0 to 8.2), HbA1c by 0.1%(0.1to0.1), systolic BP by 4.9mmHg(3.3to6.5), and Triglyceride by 9%(4to14). The level of HDL cholesterol was increased in both groups (+18 for the semaglutide group, and +19 for the switched placebo group) which might indicate that both groups were highly motivated to do physical activities as part of the clinical trial. Conclusion: Most of the metabolic syndrome parameters were found to be adversely increased after stopping GLP-1RA medications in individuals without diabetes mellitus. Such observation warrants further studies to check the safety of stopping such medications once used for individuals who are not affected by T2DM.