GLP-1 Isn’t Enough: Why Glucagon is the Key to Lasting Weight Loss

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In this lecture, Dr. Ben Bikman explores the misunderstood role of glucagon, insulin’s often-overlooked metabolic counterpart.

While insulin encourages fat storage and glucose uptake, glucagon signals the body to mobilize and burn stored energy. Contrary to popular belief, glucagon does not stimulate fat release from adipose tissue in humans. Instead, its fat-burning effects occur primarily in the liver, where it enhances fatty acid oxidation, ketone production, and energy expenditure.

Glucagon’s power lies in shifting the metabolic balance through the insulin-to-glucagon ratio—a key determinant of whether the body stores or burns fat. Ben also unpacks the liver's molecular response to glucagon, including activation of mitochondrial fat-burning enzymes and ketone formation. Human studies now confirm that glucagon increases liver fat oxidation, making it a valuable target in new weight-loss drugs.

New dual and triple agonist drugs that combine GLP-1 with glucagon receptors show superior weight loss outcomes compared to GLP-1 alone. They not only suppress appetite but also increase metabolic rate, making them potent tools in fighting obesity and fatty liver disease. However, lifestyle strategies like fasting and low-carb diets remain powerful ways to naturally leverage glucagon’s benefits without pharmaceutical intervention.

Show Notes/References:

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NOTE: The information presented is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Dr. Bikman is not a clinician—and, he is not your doctor. Always seek the advice of your own qualified health providers with questions you may have regarding medical conditions.

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