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Risk factors that should prompt consideration of B12 deficiency include advancing age (reduced stomach acid production), strict vegan or vegetarian diets, pernicious anaemia, gastrointestinal surgery (particularly gastric bypass or ileal resection), long-term use of certain medications (metformin, proton pump inhibitors, H2-receptor antagonists), nitrous oxide exposure (including recreational use), and conditions affecting the gut such as Crohn's disease or coeliac disease

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In preclinical models and early clinical trials, glucagon receptor activation increased total energy expenditure, meaning the body burns more calories even at rest

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