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Property	PrescriptionSemaglutideGLP-1 receptor agonist	PrescriptionTirzepatideDual GIP/GLP-1 receptor agonist
Primary use studied	FDA-approved for type 2 diabetes in adults (Ozempic injection and tablets, Rybelsus), including cardiovascular risk reduction and, for the Ozempic injection, kidney-disease progression; and as Wegovy injection and tablets for chronic weight management and cardiovascular risk reduction in adults with obesity or overweight. The Wegovy injection is also approved for weight management from age 12 and for MASH with moderate to advanced liver fibrosis in adults.	FDA-approved to improve glycemic control in type 2 diabetes in adults and children 10 years and older, and to reduce cardiovascular risk in adults with type 2 diabetes (Mounjaro), and for chronic weight management and moderate-to-severe obstructive sleep apnoea in adults with obesity (Zepbound).
Evidence	Strong human evidenceFDA has approved semaglutide products for several separate indications, each cleared on randomised trials reviewed by the agency: glycemic control in type 2 diabetes (Ozempic, approved 2017), cardiovascular and chronic-kidney-disease risk reduction in type 2 diabetes (Ozempic), chronic weight management (Wegovy, approved 2021), and cardiovascular risk reduction in adults with obesity or overweight and established cardiovascular disease (Wegovy). The adverse-reaction rates on the approved label come from that trial data. This rating describes the approved product, not the grey-market research-chemical vials sold under the same name.	Strong human evidenceFDA has approved tirzepatide products for four indications across two brands, each cleared on placebo-controlled randomised trials reviewed by the agency: glycemic control and cardiovascular risk reduction in type 2 diabetes (Mounjaro, approved 2022), and chronic weight management and obstructive sleep apnoea (Zepbound, approved from 2023). The adverse-reaction rates on the approved label come from that trial data. This rating describes the approved product, not grey-market vials sold under the same name.
Mechanism (proposed)	A synthetic analogue with 94% sequence homology to human GLP-1 that selectively binds and activates the GLP-1 receptor, present in brain regions that regulate appetite and caloric intake, and that also affects insulin secretion and gastric emptying. The exact mechanism behind its cardiovascular risk reduction has not been established, per its own FDA label.	A single synthetic peptide that selectively binds and activates both the GIP and GLP-1 receptors, enhancing first- and second-phase insulin secretion and reducing glucagon, both in a glucose-dependent manner, per its FDA label.
Half-life	Approximately 1 week - detectable in circulation for about 5 to 7 weeks after the last weekly 2.4 mg dose, per the approved label.	Approximately 5 days, which the label states is what enables once-weekly dosing.
US legal status	FDA-approved · prescription only	FDA-approved · prescription only
AU legal status	TGA-registered · prescription only	TGA-registered · prescription only
Key risks	Boxed warning: causes thyroid C-cell tumours in rodents; whether this occurs in humans is unknown. Contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. Gastrointestinal effects are the most common adverse reaction. In the trial data behind the Wegovy label, nausea occurred in 44% of patients versus 16% on placebo, with diarrhoea, vomiting and constipation all more common than placebo. The label states that co-administration with any other GLP-1 receptor agonist, or with another semaglutide-containing product, is not recommended - relevant to anyone combining a prescription product with a grey-market one. FDA has documented dosing errors, counterfeit product, unapproved salt-form substitution and fraudulent labelling specifically in the compounded and "research use only" semaglutide market.	Boxed warning: causes thyroid C-cell tumours in rats; whether this occurs in humans is unknown. Contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. Gastrointestinal effects are the most common adverse reaction. At the 15 mg maintenance dose in the trial data behind the Zepbound label: nausea 28%, diarrhoea 23%, vomiting 13%, constipation 11%. Delays gastric emptying and can affect the absorption of other oral medicines taken around the same time. Neither semaglutide nor tirzepatide is on the 503B bulks list, so most compounding of either now falls outside the shortage-era exception that used to apply; FDA has received hundreds of adverse event reports tied to compounded tirzepatide specifically.
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