Tirzepatide (Mounjaro, Zepbound) has emerged as the most effective anti-obesity medication for weight loss and blood pressure reduction, according to a recent study published in eClinicalMedicine. The research compared several weight-loss pharmacotherapies, with tirzepatide demonstrating the most significant reductions in body weight and the strongest antihypertensive effects, followed closely by semaglutide (Ozempic, Wegovy).
Rising Obesity Rates and the Role of Medications
Obesity rates in the United States have surged over the past decades. From 1971 to 1980, the prevalence of obesity saw only a minor increase of 0.5%. However, by 1988-1994, the rate had climbed to 23.3%, reaching 30.9% in 1999-2000. This trend has continued, with obesity now considered a chronic condition linked to cardiovascular disease, type 2 diabetes, and certain cancers. While lifestyle modifications remain a cornerstone of weight management, pharmaceutical interventions such as glucagon-like peptide-1 (GLP-1) receptor agonists have gained prominence for their ability to lower blood sugar, promote weight loss, and provide kidney and cardiac benefits.
Study Overview and Findings
Researchers conducted a comprehensive review of weight-loss medications, analyzing their impact on body weight, cardiometabolic health, mental well-being, and potential side effects. A systematic search of PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials identified 5,864 relevant articles, with 154 full-text studies included in the final analysis. The study encompassed data from 112,515 individuals with overweight or obesity, the majority of whom had weight-related health complications.
Among the pharmacotherapies evaluated, tirzepatide was prescribed to 5.8% of patients, semaglutide to 23.9%, liraglutide (Victoza, Saxenda) to 25.2%, and orlistat (Xenical) to 10.3%. Other medications studied included naltrexone/bupropion (Contrave), phentermine/topiramate (Qsymia), and standalone treatments such as phentermine (Adipex) and topiramate (Topamax).
Results showed that all medications contributed to weight loss, but tirzepatide had the greatest effect, followed by semaglutide. Combination therapies generally outperformed monotherapies in terms of weight reduction. Additionally, tirzepatide led to the most significant decreases in body weight percentage and waist circumference.
Beyond weight loss, tirzepatide demonstrated the strongest antihypertensive effects, lowering both systolic and diastolic blood pressure. It also yielded the most pronounced improvements in triglyceride levels, high-density lipoprotein (HDL) cholesterol, fasting glucose, and glycated hemoglobin A1C. In contrast, medications such as naltrexone/bupropion and bupropion alone were associated with increases in blood pressure.
Mental Health and Safety Considerations
The study also examined psychological outcomes. Tirzepatide was linked to the most significant improvements in quality-of-life scores related to weight impact, while topiramate was associated with increased depression rates. Bupropion was found to reduce depression scores, whereas naltrexone/bupropion and phentermine/topiramate were linked to higher anxiety levels. Additionally, phentermine/topiramate increased irritability, and both liraglutide and phentermine/topiramate were associated with sleep disturbances.
Although none of the medications were linked to an increased risk of serious adverse events, several—including tirzepatide, semaglutide, liraglutide, orlistat, and naltrexone/bupropion—had higher discontinuation rates due to side effects. Tirzepatide had the highest dropout rate, primarily due to adverse reactions, particularly gastrointestinal issues, which were most commonly observed with GLP-1 receptor agonists.
Implications for Weight Management
“These findings provide valuable guidance for personalized weight management and may help improve health and reduce the risk of cardiovascular and all-cause mortality in individuals living with overweight or obesity,” the researchers concluded.
As obesity continues to pose a significant public health challenge, medications such as tirzepatide and semaglutide offer promising solutions for weight loss and cardiometabolic health. However, the potential for side effects underscores the importance of individualized treatment approaches.
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