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The post hoc analysis of the STEP programme reported depressive symptoms in 2.8% of semaglutide patients against 4.1% on placeboa figure that looks reassuring until you notice the population was mostly nondiabetic and on subcutaneous 2.4 mg, which tells us nothing about lower doses of the oral drug in people with T2DM ( The FAERS signal (a reporting odds ratio of 1.87 for depression) and the adjusted ratio of 1.70 for depressed mood disorders from VigiBase both fit a risk that shows up at the level of the individual patient, even when the randomised trials, looking at groups, do not see it ( A propensity-matched cohort study in 162,253 patients found a 195% higher risk of major depression with GLP-1 RA treatment compared with matched controls ( 5.5 Clinical implications A few practical lessons come out of this case

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Have a documented body mass index (BMI) of at least 30 kg/m2 OR a BMI of at least 27 kg/m2 accompanied by a diagnosis of at least one weight-related health condition, such as hypertension, Type 2 diabetes, or dyslipidemia