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Tirzepatide is a once-weekly subcutaneous injectable medication used for chronic weight management in adults with obesity or overweight. It is a first-in-class dual agonist of both the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. Weight Loss Effectiveness Clinical trials have shown that tirzepatide leads to significant and dose-dependent weight reduction: 72-Week Results: In the pivotal SURMOUNT-1 trial, adults without diabetes taking the maximum dose (15 mg) lost an average of 20.9% to 22.5% of their body weight (approximately 50–52 lbs). Dose Comparison: Lower doses also showed substantial loss: 15.0% at 5 mg and 19.5% at 10 mg, compared to only 3.1% for the placebo group. Clinically Meaningful Loss: Over 90% of participants on the 15 mg dose achieved at least 5% weight loss, and roughly 50–57% achieved at least 20% weight loss. Head-to-Head with Semaglutide: In the SURMOUNT-5 trial, tirzepatide led to an average weight loss of 20.2% (50.3 lbs) compared to 13.7% (33.1 lbs) for semaglutide (Wegovy). How It Works Tirzepatide mimics two natural hormones released after eating: Appetite Regulation: It signals the brain to increase feelings of fullness and decrease hunger. Gastric Emptying: It slows down how quickly food leaves the stomach, prolonging satiety. Metabolic Health: It helps the pancreas release insulin and signals the liver to produce less sugar, improving blood glucose levels and insulin sensitivity. Eligibility and Administration FDA Indications: Approved as Zepbound for chronic weight management in adults with a BMI of 30+ (obesity) or 27+ (overweight) with at least one weight-related condition, such as hypertension or type 2 diabetes. Dosage Schedule: Treatment typically begins at 2.5 mg weekly for four weeks to allow the body to adjust. The dose is then increased in 2.5 mg increments every four weeks until a maintenance dose (5, 10, or 15 mg) is reached. Lifestyle Adjunct: It must be used alongside a reduced-calorie diet and increased physical activity for optimal results. Safety and Side Effects The most common side effects are gastrointestinal (GI) and often occur during the dose-escalation phase: Frequent Side Effects: Nausea, diarrhea, vomiting, and constipation. Serious Risks: Rare but serious risks include pancreatitis, gallbladder problems, severe dehydration leading to kidney issues, and potential thyroid tumors (boxed warning). Maintenance: Weight regain is common if the medication is stopped; clinical data suggests that continued use may be necessary for most patients to maintain their weight loss.