Presentation (CTI)

OBJECTIVES: Recently approved glucagon-like peptide-1 receptor agonist (GLP-1RA) based therapies, semaglutide (Wegovy®; GLP-1RA) and tirzepatide (Mounjaro®; dual GLP-1RA/gastric inhibitory polypeptide [GIP] agonist), have transformed the treatment of overweight/obesity, but have been criticised by health technology assessment (HTA) bodies for having insufficient evidence of their long-term impact on weight-related comorbidities. This study aimed to review published evidence on the real-world benefits of GLP-1RA-based therapies beyond their established effects on weight loss and glycaemic control.
METHODS: A targeted literature review was conducted in Embase and Medline using a predefined search strategy for real-world evidence (RWE) on semaglutide or tirzepatide published up until 4 June 2025. No patient population restrictions were applied. Records describing clinical outcomes beyond body weight/composition and glycaemic control were included.
RESULTS: Among the 580 records screened, 131 were relevant. GLP-1RA-based therapies had a wide range of cardio-renal-metabolic benefits including a reduced risk of major adverse cardiovascular events such as myocardial infarction (n=4 records), heart failure (n=8) and stroke (n=5), improved blood pressure (n=30), improved (n=16) or stable (n=9) renal outcomes, improved liver steatosis (n=9), reduced liver fibrosis (n=11) and liver inflammation markers (n=16), and improved lipid profile (n=47). Additionally, GLP-1RA-based therapies were associated with osteoprotective effects (n=4), reduced alcohol consumption (n=4), and a lower risk of dementia (n=3), multiple cancer types (n=2), and all-cause mortality (n=12). Compared to semaglutide, tirzepatide had a reduced risk of all-cause mortality and adverse cardiovascular or kidney events (n=2), but no differences in blood pressure or lipid profile were reported (n=1).
CONCLUSIONS: RWE suggests that GLP-1RA-based therapies have a broad range of benefits beyond weight loss and glycaemic control, which could be relevant to HTA bodies and healthcare systems when evaluating the health and economic value of these treatments. Further research is needed to understand the comparative effects of semaglutide and tirzepatide on these outcomes.