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These medications (including semaglutide, dulaglutide, and liraglutide) are typically considered when: Metformin and other oral medications have not achieved adequate glycaemic control The patient has a BMI 35 kg/m (or lower thresholds, typically by around 2.5 kg/m, for people of certain ethnic backgrounds including South Asian) Weight loss would benefit other obesity-related comorbidities Insulin therapy is being considered but would have significant occupational implications or weight gain is a concern Continuation criteria apply: for example, treatment should reduce HbA1c by at least 11 mmol/mol (1.0%) and weight by at least 3% at 6 months to be continued

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Based on preclinical and early human data, activating all three pathways is thought to reduce appetite, improve insulin sensitivity, increase energy expenditure, and support fat breakdown effects that have shown substantial weight loss results in early-phase clinical trials, including a phase 2 study published in the New England Journal of Medicine (2023)

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Rather, we notice them when the damage has been done