Among adults with obesity taking semaglutide for a year, those without type 2 diabetes lost an average of 16.9% of their body weight, while those with type 2 diabetes lost an average of 9.9%.
Mechanism
Synthesis from 1 study
People with type 2 diabetes have been exposed to high blood sugar for a long time, which makes their body less responsive to the weight-loss signal from semaglutide. As a result, the drug doesn’t reduce hunger or burn calories as effectively as it does in people without diabetes.
Most probable mechanism
In people with type 2 diabetes, the body’s response to the weight-loss hormone semaglutide is weaker because their cells have become less sensitive to it over time due to long-term high blood sugar and insulin resistance. This means the drug doesn’t reduce hunger or boost calorie burning as much as it does in people without diabetes.
Chronic hyperglycemia and hyperinsulinemia in type 2 diabetes lead to downregulation and desensitization of GLP-1 receptors in hypothalamic neurons and vagal afferents.
Reduced GLP-1 receptor signaling decreases the suppression of appetite and reduces postprandial satiety signals sent to the brain.
Diminished GLP-1-mediated activation of brown adipose tissue and sympathetic nervous system output lowers resting energy expenditure.
Evidence from Studies
Supporting (1)
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Weight loss and cardiovascular disease risk outcomes of semaglutide: a one-year multicentered study
Contradicting (0)
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