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Metformin acts mainly by inducing liver and skeletal muscle serine/threonine kinase B1 (LKB1), which activates AMP-activated protein kinase (AMPK) by phosphorylating Thr 172 of the AMPK chain [2]

Obesity SURMOUNT-1 Trial In adults with obesity (without diabetes): Tirzepatide (15 mg) : 20.9% average body weight reduction over 72 weeks Semaglutide (2.4 mg) (based on STEP trials): ~14.9% average reduction STEP 5 Long-Term Results Semaglutide also demonstrated durable effects: At 104 weeks, patients maintained ~15% weight loss on semaglutide 2.4 mg (STEP 5) SELECT Trial Cardiovascular Benefit Semaglutide significantly reduced major adverse cardiovascular events by 20% in people with obesity and pre-existing heart diseaseindicating benefit beyond weight loss

March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ

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