Overweight and Obesity: A Comprehensive Perspective

Overweight and obesity are major contributors to the global burden of noncommunicable diseases. As these conditions continue to rise worldwide, China is projected to have the largest affected population by 2050. This alarming trend underscores the urgent need for effective, evidence-based treatment strategies tailored to regional demographics and disease patterns.

A recent large-scale phase 3 trial sheds light on the potential of mazdutide, a once-weekly dual GLP-1 and glucagon receptor agonist, to address obesity in the Chinese population.1 The study enrolled 610 adults with overweight or obesity and evaluated weight loss outcomes over 32 weeks. Participants received either 4 mg or 6 mg of mazdutide or a placebo. Both treatment arms achieved significant placebo-adjusted reductions in body weight, 10.54% with 4 mg and 13.00% with 6 mg. Notably, 44% of individuals in the higher-dose group achieved a weight reduction of 15% or more.

Beyond weight loss, the trial demonstrated comprehensive metabolic benefits, including improvements in body composition, glycemic markers, blood pressure, liver enzymes, and quality of life indices. These findings reinforce the view that anti-obesity medications should not be assessed solely by reductions in body mass index, but rather by their broader impact on health and function.

Interestingly, the study population was younger (average age 34 years) and metabolically healthier than participants in comparable international trials. Despite lower rates of prediabetes and hypertension, this cohort exhibited high levels of dyslipidemia (62.3%) and metabolic dysfunction–associated fatty liver disease (48.9%). These findings suggest a shift in the phenotype of obesity in China and highlight the need for early, targeted intervention.

These results emphasize the importance of individualized, risk-based approaches to obesity treatment. Simple, linear treatment algorithms based on BMI thresholds risk overlooking the nuanced profiles of patients who may benefit from earlier pharmacologic therapy. The trial also draws attention to the long-term health consequences of obesity beginning in early adulthood, where cumulative years of life lost may be substantial.

While mazdutide represents a promising pharmacological tool, medication alone will not resolve the obesity epidemic. A multifaceted approach — combining lifestyle modification, policy intervention, education, and equitable access to care — will be essential. Nonetheless, this trial marks meaningful progress in expanding the therapeutic landscape for obesity and tailoring solutions to the evolving health challenges of diverse populations.

Source:  Aroda V, Perreault L. Overweight and Obesity — Capturing the Whole Picture. N Engl J Med. 2025. doi:10.1056/NEJMe2505819. Available from: