Just 4.5% of adults in Japan are classified as obese according to the World Health Organization’s standard measure, but experts say that this doesn’t seem to match the prevalence of obesity-related health problems. Credit: Makiko Tanigawa/Getty
It is estimated that by 2030, about one in six people globally will be obese — a condition characterized by an unhealthy excess of body fat associated with elevated risk of cardiovascular disease, diabetes, musculoskeletal disorders and certain types of cancer. Obesity is often associated with an accumulation of visceral fat around internal organs, and in the past has been viewed in simplistic terms as a weight management issue.
However, obesity is now recognized as a complex, chronic disease influenced by genetics, physiology, environment, education and brain function, and has become the subject of increasingly intensive research into effective prevention and treatment strategies.
The growing understanding of this disease, and in particular the molecular mechanisms underlying appetite and energy utilization, has led to a proliferation of pharmacological treatment options that can aid weight loss by targeting central nervous system pathways that regulate sensations of satiety and fullness, as well as digestion and metabolism1.
The advent of such anti-obesity drugs and their increasing availability has catalysed a change in how the disease is managed and treated.
“In conjunction with lifestyle changes, including diet and exercise, anti-obesity medications can lead to significant weight loss and reduction of visceral fat,” says Soichi Sakai, General Manager of the Clinical Research Division of Taisho Pharmaceutical Co., based in Tokyo, Japan.
He argues that improving health literacy around anti-obesity drugs, as part of a holistic solution, also including lifestyle changes, could help with the management of obesity and obesity-related diseases.
Important differences
In Japan, while the incidence of weight-related type 2 diabetes and cardiovascular disease is on the rise, the proportion of the population classified as being clinically obese remains 10 times lower than in the US.
Sakai suggests that one of the reasons for this is that the Body Mass Index (BMI) widely used to screen for obesity doesn’t account for differences in visceral fat distribution between populations that have Asian or European heritage2.
“The pathological features of obesity in Japan differ from those in the West and other parts of the world,” Sakai says. “Asian populations have a higher risk of cardiovascular disease and type 2 diabetes at a much lower BMI than Europeans.”
BMI is calculated as weight in kilograms divided by the height in metres squared. According to the World Health Organization, an adult with a BMI over 30 is classified as obese. Using this criterion, only 4.5% of adults in Japan are classified as obese, which does not match the prevalence of obesity-related health problems, Sakai says.
The Japan Society for the Study of Obesity recommends instead using a BMI of 25 as the threshold for obesity for the Japanese population. It also recommends using waist measurements, 85 centimetres or more in men and 90 centimetres or more in women, as an indicator of excessive visceral fat accumulation and associated increased risk of obesity-related disorders.
Researchers argue that, by using these criteria, those at risk of obesity will be identified sooner, giving an opportunity for early intervention with treatment and prevention strategies.
Anti-obesity drugs work best when combined with lifestyle changes such as reducing fast food intake and increasing regular exercise. Credit: Oscar Wong/Getty
More treatment options
Japan’s clinical guidelines stipulate that obesity disease, defined as a clinical need for weight loss, can be treated pharmacologically and surgically. However, until this year, the only drug approved and available in Japan for the treatment of obesity disease was the appetite suppressor mazindol, which is a stimulant that can only be taken for short periods.
“Mazindol has been used to a limited extent for patients with a BMI exceeding 35 as a short-term complement to diet and exercise in the treatment of obesity disease,” says Sakai. “The approval of semaglutide in March 2023 offers an alternative that can be prescribed for longer periods of time and for a wider target population.”
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that mimics the GLP-1 hormone — a biomolecule released in the gut in response to eating that prompts the production of insulin. In higher doses, it also triggers the brain to suppress appetite.
Prescription drugs such as semaglutide are now widely used in other countries to treat patients with diagnosed obesity disease, and has the same potential in Japan. But preventing the development of obesity in the first place through early intervention using a combination of strategies is equally important.
In February 2023, a different drug, orlistat, was approved in Japan as the first over-the-counter medicine for the reduction of visceral fat in the treatment of obesity. Orlistat is a lipase inhibitor that reduces the absorption of dietary fat, and in combination with lifestyle changes can be used to treat excessive accumulation of visceral fat before obesity disease develops.
“Prior to this, the only over-the-counter option in Japan for obesity was traditional Chinese herbal medicine,” says Toru Fujita, Manager of the Clinical Research Division of Taisho Pharmaceutical Co. “This situation emphasizes the need for new clinically supported3,4 drugs.”
Holistic approach to weight loss
Sakai says that, as the number of drugs for long-term weight management expands, it is important to address some of the misconceptions surrounding these medications.
“Many people think that they can lose weight just by taking the medication alone,” Sakai says, “but anti-obesity drugs work best when combined with a balanced diet, regular exercise, and lifestyle changes; they should be part of a holistic approach.”
With improved health literacy and access to effective anti-obesity drugs in combination with appropriate lifestyle changes, Fujita points out we now have very effective approaches to prevent, manage and treat obesity and weight-related health problems, which will ultimately translate into reduced national healthcare costs.
“Japan’s ageing population is leading to a rapid escalation in public spending on health,” says Fujita. “By attenuating the progression of obesity, anti-obesity drugs offer a solution for reducing obesity-related health care expenses. Through assisted lifestyle changes supported by such tools as lifestyle improvement smartphone apps and by taking anti-obesity drugs when appropriate, we can foster an environment where people can enjoy healthier and longer lives.”
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