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Remarkably, tirzepatide (15 mg per week) reduced body weight by up to 20.9% after 72 weeks [93], which was associated with reduced waist circumference and an overall improvement in individuals clinical profile
Several physiological mechanisms explain why rapid weight loss promotes gallstone formation: Altered bile composition : During significant caloric restriction and rapid fat mobilisation, the liver secretes increased amounts of cholesterol into bile whilst bile salt secretion remains relatively constant, creating cholesterol-supersaturated bile Reduced gallbladder motility : Decreased food intake, particularly reduced dietary fat, means less frequent gallbladder contraction and emptying, allowing bile to stagnate and cholesterol crystals to form Increased cholesterol mobilisation : As adipose tissue is broken down, cholesterol is released into the circulation and subsequently excreted via bile Studies of patients undergoing bariatric surgeryanother intervention causing rapid weight losshave demonstrated gallstone formation rates of 3050% within the first year post-operatively when prophylactic measures are not employed, though many of these stones remain asymptomatic
Phosphodiesterase-5 (PDE5) inhibitors such as sildenafil are often effective first-line treatments and are generally safe to use alongside GLP-1 medications, though they are contraindicated with nitrate medications and riociguat, and should be used with caution in unstable cardiovascular disease or if taking alpha-blockers
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