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The dedicated cardiovascular trial did not find excess major events and reported lower all-cause mortality, but resting heart rate remains a titration marker rather than a one-time measurement. How to Titrate, and the Cost of Going Too Fast The final dose shapes the endpoint, but escalation speed is the largest modifiable driver of side effects

Risk increases significantly after 2+ years of use Post-bariatric surgery patients gastric bypass removes or bypasses the sites of intrinsic factor production and B12 absorption People with autoimmune conditions pernicious anemia (anti-intrinsic factor antibodies) and autoimmune gastritis directly block absorption People with GI conditions Crohns disease (especially ileal involvement), celiac disease, SIBO, and chronic H

2010 Mar;59(3):343-9

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