From the Guidelines
Tirzepatide is a highly effective medication for weight loss in obese individuals without diabetes, with a recommended starting dose of 2.5 mg injected subcutaneously once weekly, gradually increasing to 5 mg, 7.5 mg, 10 mg, and potentially up to 15 mg weekly, depending on tolerance and response, as supported by a recent study published in JAMA in 2023 1. The medication works by mimicking two hormones—GLP-1 and GIP—which help regulate appetite, slow gastric emptying, and improve insulin sensitivity. In clinical trials, participants lost approximately 15-20% of their body weight over 72 weeks, with the 15 mg dose of tirzepatide resulting in a mean weight loss of 20.9% 1. Common side effects include nausea, vomiting, diarrhea, and constipation, which typically improve over time. Tirzepatide should be used alongside lifestyle modifications including diet and exercise for optimal results. Patients should stay well-hydrated and start with smaller, more frequent meals to minimize gastrointestinal side effects. The medication is contraindicated in pregnancy and should be used cautiously in those with a history of pancreatitis or medullary thyroid cancer. Some key points to consider when prescribing tirzepatide include:
- The importance of slow dose escalation to minimize gastrointestinal side effects
- The need for regular monitoring of patients for potential side effects and adjustments to the treatment plan as needed
- The potential benefits of tirzepatide on cardiovascular risk factors, such as lipids and blood pressure, in addition to its effects on weight loss 1. It's also worth noting that tirzepatide has been compared to other weight loss medications, such as semaglutide and liraglutide, and has been shown to result in greater weight loss in some studies 1. Overall, tirzepatide is a valuable treatment option for obese individuals without diabetes, and its use should be considered in conjunction with lifestyle modifications and regular monitoring for potential side effects.
From the Research
Tirzepatide for Weight Loss in Obese Non-Diabetics
- Tirzepatide is a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist that has shown substantial and sustained reductions in body weight in people with obesity 2.
- In a phase 3 double-blind, randomized, controlled trial, tirzepatide once weekly provided significant weight loss in adults with a body-mass index (BMI) of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes 2.
- The mean percentage change in weight at week 72 was -15.0% with 5-mg weekly doses of tirzepatide, -19.5% with 10-mg doses, and -20.9% with 15-mg doses, compared to -3.1% with placebo (P<0.001 for all comparisons with placebo) 2.
Efficacy and Safety of Tirzepatide
- Tirzepatide has been shown to be well-tolerated with a safety profile similar to GLP-1 receptor agonists, and it results in clinically important improvements in multiple obesity-related complications, including sleep apnea, metabolic-dysfunction associated steatohepatitis, heart failure with preserved ejection fraction, and diabetes prevention 3.
- The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation 2, 4.
- Three years of treatment with tirzepatide in persons with obesity and prediabetes resulted in substantial and sustained weight reduction and a markedly lower risk of progression to type 2 diabetes than that with placebo 4.
Comparison with Other Weight Loss Treatments
- Tirzepatide has been compared to other weight loss treatments, including semaglutide, and has shown promise for even greater weight loss efficacy 5.
- The use of tirzepatide as a primary weight loss therapy has been explored in several phase 3 clinical trials, which have demonstrated superior weight loss efficacy compared to previously approved medications 6.