Tirzepatide Dosing for Weight Loss Is Successful

Tirzepatide, a type 2 diabetes drug, led to a reduction in body weight, amounting to 64 pounds in adults without the disease but with other weight-related conditions.

Manufactured by Eli Lilly and Company, tirzepatide is a once-weekly GIP (glucose-dependent insulinotropic polypeptide) receptor and GLP-1 (glucagon-like peptide-1) receptor agonist. The drug activates the body's receptors for GIP and GLP-1, which are natural incretin hormones and play an important role in appetite regulation.

GLP-1 agonists, some of which are intended for treating type 2 diabetes, have recently skyrocketed in popularity as a treatment of obesity, reaching about 40 million prescriptions in the United States last year.

The U.S. Food and Drug Administration (FDA) has approved tirzepatide, sold under the brand name Mounjaro, to improve blood sugar control in adults with type 2 diabetes in combination with diet and exercise.

Phase 3 SURMOUNT-3 double-blind, randomized placebo-controlled clinical trial, the findings of which were published in Nature Medicine, evaluated tirzepatide in adults with obesity or overweight with weight-related comorbidities, excluding type 2 diabetes.

The researchers recruited 806 participants who were enrolled in the 12-week intensive lifestyle intervention that included a low-calorie diet, exercise, and frequent counseling sessions. At the beginning of the study, the mean weight of the participants was 241.4 lb. (109.5 kg). During the 12-week period, they experienced a 6.9% reduction in body weight.

Of those, 579 (71.8%) participants achieved at least 5% of body weight reduction and were randomized to either tirzepatide or placebo for 72 weeks. Most (66.1%) had a medical history of one or more obesity-related complications.

The dose of 2.5 mg was increased by 2.5 mg every four weeks until the maximum tolerated dose was achieved. Those who tolerated 15 mg continued on 15 mg as their maximum tolerated dose, while the participants who tolerated 10 mg, but did not tolerate 15 mg, continued on 10 mg as their maximum tolerated dose.

The tirzepatide group had an average weight reduction of 26.6% of their body weight (29.2 kg or 64.4 lb.), compared with 3.8% (4.1 kg or 9.0 lb.) in the placebo group.

"In this study, people who added tirzepatide to diet and exercise saw greater, longer-lasting weight reduction than those taking placebo," said Jeff Emmick, M.D., Ph.D., senior vice president of product development at Eli Lilly, in a press release. "While intensive lifestyle intervention is an important part of obesity management, these results underscore the difficulty some people face maintaining weight loss with diet and exercise alone."

Moreover, maximum doses of tirzepatide significantly more effective at reducing waist circumference than placebo, −14.6 cm (−5.7 in) versus 0.2 cm (0.07 in), respectively.

The study suggests that Eli Lily's drug for weight loss is successful if taken after losing about 5% to 10% of the body weight with lifestyle intervention.

Side effects of tirzepatide

Common side effects reported were gastrointestinal-related, such as nausea, diarrhea, constipation, and vomiting, and they were generally mild to moderate in severity. About one in 10 participants taking tirzepatide chose treatment discontinuation and stopped the study due to adverse reactions, compared to 2.1% in the placebo group.

A recent study has associated using GLP-1 agonists with an increased risk of pancreatitis, bowel obstruction, and gastroparesis (stomach paralysis). The authors warned that "people who are otherwise healthy may be less willing to accept these potentially serious adverse events" when considering using the drugs for weight loss.

Earlier this year, a Louisiana woman filed a lawsuit against manufacturers of Mounjaro and Ozempic, claiming she experienced stomach paralysis after using the two diabetes drugs. According to the complaint, the stomach issues caused by the drugs led to multiple hospitalizations, including emergency room visits.

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