About tirzepatide
Tirzepatide was originally developed to treat Type-2 diabetes but has since become a leading anti-obesity medication. It is a dual agonist of the GLP-1 and GIP receptors, meaning it activates two distinct hormonal pathways to reduce appetite, improve metabolic rate, and support sustained weight loss.
Unlike its predecessor Semaglutide (which only targets GLP-1), Tirzepatide showed 5-7% more weight loss in clinical trials. Compared to Retatrutide, a triple agonist, Tirzepatide accomplished nearly the same weight loss but over a longer period (72 weeks vs. 48).
Mechanism of action
- GLP-1: Suppresses appetite and increases feelings of fullness after eating.
- GIP: Promotes insulin secretion and supports energy balance through receptors in the hypothalamus.
Benefits
- Average weight loss of 24.7% after 72 weeks
- Reduces appetite and cravings
- Enhances satiety and energy balance
- Supports fat oxidation and metabolism
- Improves insulin sensitivity and blood sugar control
Possible side effects
Often mild and temporary. Affected only about 25% of people in trials.
- Injection site reaction (redness, swelling, itching)
- Nausea
- Vomiting
- Diarrhea
- Constipation
- Decreased appetite
- Fatigue
- Dyspepsia (indigestion)
- Abdominal pain
- Burping (may have sulfur smell)
- Hair loss
Rare but serious risks
- Thyroid C-Cell Tumors
- Pancreatitis
- Gastroparesis (stomach paralysis)
- Hypoglycemia (if used with insulin)
- Gallbladder disease
- Kidney issues (linked to dehydration)
- Pulmonary aspiration under anesthesia. Always disclose Tirzepatide use to surgical teams.
Interactions
- Insulin and insulin-stimulating drugs: includes all forms of insulin, sulfonylureas (glipizide, glyburide, glimepiride), and glinides (repaglinide), due to the increased risk of hypoglycemia
- Oral medications: Tirzepatide may interfere the absorption of oral medications
- Oral birth control medications: increases the likelihood of additive GI effects, may lead to excessive appetite suppression, and increases the risk of hypoglycemia
- Growth hormone/GH analogs: interactions have been reported with Somatropin, Lonapegsomatropin, Somapacitan
- Alcohol: increases the risk of hypoglycemia and worsens nausea and dehydration
- Dehydration risk: dehydration places excessive stress on the kidneys, and may lead to kidney damage. This risk increases with concurrent use with ACE inhibitors, diuretics, ARBs, and heart failure regimens
- Berberine/Metformin: increased risk of hypoglycemia
- Chromium/Insulin sensitizers: increased risk of hypoglycemia
- Appetite suppressants: added risk of eating disorder/anorexia
- Stimulants: excessively diminished appetite and GI intolerance overlap
- Large, greasy meals: increases the likelihood of nausea
Peptide interactions
Severe
- Other GLP peptides: receptor redundancy and desensitization
- Tesamorelin: elevated glucose levels
- IGF-1 LR3/DES and strong ghrelin agonists (e.g. GHRP 2 and 6): may oppose or significantly amplify Tirzepatide's metabolic signaling
Moderate
- IGF-1 LR3 and IGF-1 DES: risk of hypoglycemia and rapid glucose uptake
- CJC with DAC: blunts GLP metabolic benefit
- GHRP-2, GHRP-6, Hexarelin: can counter appetite suppression
- BAM-15: watch appetite suppression and fatigue
- LL-37: may worsen nausea and inflammation
- Oxytocin: monitor excessive appetite loss
Contraindications
- Do not use if pregnant or breastfeeding
- Do not use with a personal or family history of Medullary Thyroid Carcinoma or MEN 2 (Multiple Endocrine Neoplasia)
- Do not use if you have Type-1 diabetes, diabetic retinopathy, or severe GI disease
- Do not use if you are allergic or hypersensitive to Tirzepatide