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Metformin is the first-line medication for type 2 diabetes in over 80 percent of global endocrinology guidelines. Evidence: International Diabetes Federation and American Diabetes Association both recommend it as first choice for new diagnoses. About 60 percent of people who take metformin experience weight loss, averaging 3.5 to 4 kilograms (around 8 pounds) per year. Evidence: Multiple meta-analyses (e.g., Diabetes Obes Metab, 2018) show this effect in both diabetics and people with prediabetes or PCOS. Metformin is linked to a lower risk of certain cancers, especially in people with diabetes. Evidence: Studies suggest a 10–40 percent reduction in risk for some cancers (like colon, breast, prostate), but evidence is mixed and not yet conclusive for non-diabetics. Metformin acts mainly by reducing glucose production in the liver (gluconeogenesis), activating the AMPK pathway. AMPK is a central energy sensor, signaling the body to burn fat and save energy. This is a well-documented, universal mechanism in all users. Metformin increases fat burning and improves insulin sensitivity, making it effective for both weight loss and improving blood sugar control. Evidence: Consistent findings in both clinical trials and real-world practice. More than 30 percent of metformin users experience mild gastrointestinal side effects (nausea, bloating, diarrhea), but only about 5 percent stop due to these effects. Evidence: Meta-analyses, e.g., in Diabetes Care, confirm these percentages. Long-term metformin use causes vitamin B12 deficiency in about 5–10 percent of users. Recommendation: Regular B12 monitoring every 2–3 years if on long-term therapy. Supplementation can fully correct the deficiency. Metformin is not recommended for people with severe kidney, liver, or heart failure due to the risk of lactic acidosis (extremely rare—much less than 1 percent if kidneys are normal). Metformin may extend lifespan in animals by about 10 percent. Evidence: Animal studies show this reliably. The TAME trial (for humans) is ongoing, with results expected in 2026. Metformin is frequently used “off-label” in people without diabetes (e.g., prediabetes, PCOS), but current guidelines do not recommend it for weight loss in healthy people due to limited long-term safety data in this group. Disclaimer: This information is provided for general knowledge and educational purposes only. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always consult with your doctor for any questions or concerns you may have about your health.

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Dr. Christy shares her excitement about Zepbound - going over the data and the reasons why this is moving obesity medicine forward. REFERENCES: https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-zepboundtm-tirzepatide-chronic-weight SURMOUNT-1 data: https://www.nejm.org/doi/full/10.1056/NEJMoa2206038 SURMOUNT-2 data: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01200-X/fulltext

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