Tirzepatide: A novel anti-obesity drug |
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Tirzepatide: A novel anti-obesity drug
Dr Sanjay Kalra, DM (AIIMS); President-elect, SAFES, Bharti Hospital, Karnal, India; and Dr Sameer Aggarwal, Dept. of Endocrinology, Apex Specialty Hospital, Rohtak,  12 May 2022
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Obese and overweight adults taking once weekly tirzepatide achieved a weight loss up to 22.5% amounting to 22 kg, according to results from the SURMOUNT-1 clinical trial.1

The multi-site international SURMOUNT-1 trial enrolled 2539 participants from nine countries - Argentina, United States, Japan, Mexico, Brazil, Russia, China, Taiwan including India. The participants were obese or overweight, average weight 105 kg, and had a minimum of one comorbid condition such as heart disease, hypertension, dyslipidemia, or obstructive sleep apnea but not type 2 diabetes. The objective of the trial was to evaluate the safety and efficacy of tirzepatide 5 mg, 10 mg and 15 mg weekly administered subcutaneously (SC) once a week in reducing body weight as an adjunct to a reduced-calorie diet and increased physical activity compared to placebo for a duration of 72 weeks. The researchers also examined the percentage of the study subjects who achieved 5% body weight reduction at 72 weeks compared to placebo.

Data analysis showed that participants who were taking 5 mg of tirzepatide lost on average 16 kgs, those on 10 mg lost 22kg, while participants on 15 mg lost 24 kgs amounting to a weight loss of 16% vs 21.4% vs 22.5%, respectively. On the other hand, the weight loss in the placebo recipients was just 2 kg or 2.4%. In addition, 89% (5 mg) and 96% (10 mg and 15 mg) of subjects taking tirzepatide lost minimum 5% of body weight compared to 28% receiving placebo. Fifty-five percent of patients on tirzepatide 10 mg and 63% patients on 15 mg tirzepatide achieved a weight loss of at least 20% of their body weight, compared with just 1.3% taking placebo.

Adverse effects were mostly gastrointestinal-related and included symptoms like nausea, vomiting, diarrhea, constipation. These were generally mild to moderate and more prevalent with the higher doses of tirzepatide. Overall, more patients in the 10 mg and 15 mg tirzepatide doses discontinued their treatment compared to those taking the 5 mg dose; 14.3% (5 mg) vs 16.4% (10 mg) vs 15.1% (15 mg), respectively. In the placebo group, 26% stopped their treatment.

Tirzepatide is a new experimental drug under investigation for the treatment of obesity; it is a dual glucagon-like peptide-1 (GLP-1) receptor / glucose-dependent insulinotropic polypeptide (GIP) receptor agonist i.e., it combines the actions of the two natural hormones into one molecule and therefore has been dubbed as “twincretin”.

 

These results from the phase III SURMOUNT-1 trial investigating various doses of tirzepatide show striking reduction in body weight. The highest dose (15 mg) was most effective leading to more than 20% weight loss, which was comparable to that achieved with bariatric surgery. And more than 90% of participants on higher doses (10 mg and 15 mg) achieved at least 5% reduction in body weight. It had a similar safety profile as other incretin-based therapies approved for obesity treatment. 

Given these intriguing results, tirzepatide could be a potentially useful addition to the armamentarium of anti-obesity treatments and revolutionize its management.

SURMOUNT-1 is the first phase III trial of the global SURMOUNT trial investigating 5000 people with obesity or overweight in six clinical trials. Results from SURMOUNT-2, SURMOUNT-3, and SURMOUNT-4 are anticipated in 2023.

Reference

  1. https://investor.lilly.com/news-releases/news-release-details/lillys-tirzepatide-delivered-225-weight-loss-adults-obesity-or
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