London School of Hygiene & Tropical Medicine

Written by Ho Ying Edwina Sze, MSc Nutrition for Global Health student

In a surprising development, South Africa faces a shortage of insulin pens due to Novo Nordisk redirecting these devices for use with GLP-1 receptor agonists, the latest drugs in obesity management. This shift forces diabetic patients to revert to the more painful vial and syringe method for insulin administration. This situation highlights the complex balance between advancing chronic weight management and meeting essential diabetes care needs.

As of 2022, 1 in 8 people in the world were living with obesity, while 43% of adults aged 18 and over were overweight. This means over 800 million people living with obesity globally. Worldwide obesity rates have been increasing at alarming rates, with adult rates having doubled since 1990 while adolescent obesity has quadrupled (find out more obesity statistics here).

Who is affected most by obesity?

In nations witnessing the most rapid surges in obesity rates, we often find those categorised as low- to middle-income countries (LMICs). Despite strides in growth and development, these countries grapple with enduring challenges such as poverty, limited healthcare access, educational barriers, and infrastructural limitations.

The South Pacific region is noted for its high obesity rates, with Kiribati and Tonga projected to have the highest rates globally by 2035, reaching 67%, followed closely by Samoa at 66%, French Polynesia at 65%, and Micronesia at 64%. The USUS also ranks highly with a projected rate of 58% by 2035. In contrast, Asia displays the lowest projected obesity rates, with Vietnam at 7%, followed by Japan at 8%, Singapore at 9%, and both India and Bangladesh at 11%.

There are also disparities in obesity within countries. For instance, obesity is heavily impacted by racial disparities in health and healthcare in the US, which culminate in a life expectancy 4 years shorter for African Americans than white Americans. Moreover, there is increasing awareness and research on rural/urban health disparities including healthcare provision, health-related behaviours and health status. In the US, access to healthcare is often limited in rural areas compared to urban locales. Additionally, rural residents typically engage in less physical activity, leading to higher levels of obesity. These factors contribute to poorer overall health, elevated instances of type 2 diabetes, and, sadly, increased mortality rates compared to their urban counterparts. In contrary, the UK experiences the opposite trend whereby health status worsens with increasing levels of urbanisation. Different countries have various trends in health outcomes and urbanisation as get attributed to their unique healthcare system, social structure, behaviours and socioeconomic development. However, higher rates of obesity are generally found in lower resourced populations.

Why are obesity rates increasing?

The global rise in obesity since 1990 can be attributed to a complex interplay of various factors, including changes in our diet, physical activity levels, environmental influences, socioeconomic status, and cultural norms.

The nutrition transition describes the predictable shifts in a population’s diet and energy expenditure as a result of modernisation, urbanisation and economic development. For example, as income rises, consumption of high-calorie and ultra-processed foods generally increases along with decreases in physical activity levels, leading to obesity. In many high-income countries, the commercial food environment and aggressive advertising by large food corporations of unhealthy foods and beverages have been identified as a driver of unhealthier choices among adolescents, highlighting the need to address the determinants of obesity at all ages and all levels of the food system. (See more research by Natalie Savona and Dr Nason Maani)

Moreover, obesity rates tend to be higher among individuals from lower socioeconomic backgrounds as they often have more limited access to healthy food options, higher stress levels and a lack of resources for physical activity.

There are additionally cultural norms and traditions around food that contribute to weight gain, such as celebratory feasts, large portion sizes, regional cuisines rich in high-calorie foods. Certain cultures also celebrate a bigger body size.

Why is the obesity epidemic a problem?

According to the World Health Organization in 2019, higher-than-optimal body-mass index (BMI) resulted in an estimated 5 million deaths from non-communicable diseases (NCDs) such as cardiovascular diseases, diabetes, and some cancers. High BMI was the 5^th highest contributor to deaths globally in 2019, while high blood pressure – of which high BMI is a known risk factor – was the top contributor.

Being overweight or obese in childhood and adolescence is also associated with a greater risk and earlier onset of NCDs in later life. Additionally, obesity during youth has immediate health impacts and stigma about can affect school performance and quality of life.

The financial consequences of the obesity epidemic cannot be overlooked. Failure to take action is projected to result in an annual global expense of US$ 3 trillion by 2030 and a staggering US$ 18 trillion by 2060 due to overweight and obesity. Rising obesity rates among lower socio-economic groups in low- and middle-income countries is rapidly turning this problem – previously linked exclusively to high-income nations – into a global concern.

How do we treat obesity?

Currently, the main way to treat obesity is through lifestyle changes involving eating a healthy, reduced-calorie diet and regular exercise. Psychological support may also be recommended to change the way individuals think about food, but motivation to create lifestyle changes is not always sufficient. Eating habits and exercise routines are predominantly influenced by our environmental and societal factors surrounding, which limit our personal choices. Obesity should be seen as a collective responsibility rather than an individual one, and the solutions lie in establishing supportive environments and communities where healthy diets and regular physical activity are easily accessible and affordable aspects of daily life.

Consequently, when lifestyle changes are insufficient for an individual to lose enough weight, doctors may prescribe medication and in rare cases, weight loss surgery. Weight loss drugs including Ozempic, Wegovy, Victoza/Saxenda, and Mounjaro have recently risen in popularity.

What are weight loss drugs?

Ozempic and Wegovy both use the active ingredient semaglutide, but the Wegovy contains a higher dose and was developed specifically for the treatment of overweight and obesity. Semaglutide is a glucagon-like peptide 1 (GLP-1) analogue, meaning it has the same biological actions as GLP-1, including stimulating post-meal insulin release to lower blood sugar, reducing glucagon secretion to prevent more glucose entering the blood, delaying the time it takes for food to empty out of your stomach, and increasing how full you feel after eating. These effects induce weight loss by reducing your hunger, as a result lowering food intake.

Victoza (also sold under the brand name Saxenda) contains the active ingredient liraglutide which is also a GLP-1 analogue with the same biological actions. However, liraglutide remains active in the body for a shorter duration, so liraglutide requires a daily dose rather than the once-weekly dosing of Ozempic and Wegovy.

Mounjaro contains the active ingredient tirzepatide, which is a GLP-1 analogue that also activates the gastric inhibitory polypeptide (GIP) receptor, resulting in similar biological actions to lower blood sugar and reduce hunger.

Current guidelines for their prescription differ in the UK and US, being either prescribed for type 2 diabetes mellitus or chronic weight management. See the table below:

It should be noted that all the drugs should be used in addition to a reduced calorie diet and increased physical activity.

Mounjaro was approved by the US FDA for chronic weight management in November 2023 due to new evidence found in a randomized controlled trial, having originally been approved for adults with type 2 diabetes mellitus only. As of June 2024, the NICE guidelines in the UK have not changed and it remains that Mounjaro should only be prescribed for patients with Type 2 diabetes mellitus.

How successful are the drugs?

Adults who are obese (or overweight and have one or more weight-related conditions) and who do not have diabetes, reduced their weight by an average of 14.9% when using Wegovy alongside lifestyle intervention.

Research has shown that when liraglutide is used together with a reduced-calorie diet and increased physical activity, it is more effective for weight loss in overweight and obese adults without diabetes than lifestyle changes alone, with an average weight loss of 8.0% over 56 weeks. Liraglutide has also been shown to be effective for overweight and obese adolescents when coupled with lifestyle therapy over 56 weeks.

Overall, there is strong evidence that these drugs are effective in achieving weight loss when coupled with lifestyle interventions.

Anecdotally, these drugs have also been successful. Many prominent figures, such as Oprah Winfrey and Tesla CEO Elon Musk, have used weight loss drugs, with Jimmy Kimmel joking about Ozempic during the 2023 Oscars. These drugs have undoubtedly been rising in popularity with supply shortages in many areas. However, this trend is becoming problematic as drugs such as Ozempic have increasing rates of off-label use, while interfering with supply for patients who need it most.

If these drugs are so effective, why isn’t everyone prescribed them?

While it may seem that these drugs offer a novel way of treating obesity, there are several problems, including supply and availability. For instance, Wegovy has so far only launched in the US, UK, Germany, Norway, its home market Denmark, Japan, and has been approved most recently in China. Likewise, Ozempic and Mounjaro are available in limited countries and have experienced shortages in supply.

While the UK supplies Wegovy and Ozempic through the NHS, these drugs are costly in the US, where Ozempic can cost more than $1,000 a month and is not covered by most insurance plans. Although sold in these countries, oftentimes the most affected groups cannot access such drugs.

In the UK, Wegovy prescription is limited through specialist weight management services only, but off-label use for weight loss (rather than type 2 diabetes) is causing supply issues for Ozempic. In the US, Wegovy has seen recurrent shortages, driving providers to prescribe Ozempic off-label, despite the manufacturer Novo Nordisk emphasising that the two drugs are not interchangeable.

Novo Nordisk CEO, Lars Fruergaard Jørgensen, has said it could take years to fulfill the demand for Ozempic and Wegovy. Off-label Ozempic use is particularly problematic as patients who need to take Ozempic for type 2 diabetes are unable to reliably access it. Novo Nordisk guidance says doctors are expected to use healthcare resources “appropriately and responsibly” and should inform clinical decision making. It suggests doctors inform patients about the supply issues and importance of identifying “when another therapeutic approach is needed” and should also liaise with pharmacists about other options “should a switch in medicines be required”.

“While your primary duty is to your patient, you must consider the needs of all patients and balance these where resources are limited.” - Novo Nordisk

However, some physicians argue that off-label prescription is not necessarily negligent or malicious. Obese patients with associated cardiovascular disease need long-term medical weight management to help manage their heart condition, and Semaglutide shows evidence of benefitting heart health. Some doctors argue that it is ethically problematic to place the needs of patients with diabetes above those with severe weight issues, and the prescription guidance discriminates against people with obesity. Considering the surging global overweight and obesity rates and slow approval of weight loss drugs, it is likely that healthcare providers will continue to use any drug that proves useful, even off-label, until more effective drugs are approved.

However, these drugs are not the answer for everyone due to side effects such as vomiting, nausea, headache, and fatigue. Additionally, there is a lack of data on long-term outcomes. There has been evidence that liraglutide weight loss is sustained after 5 years of treatment and evidence to suggest that the extent of weight regain after treatment is less than the weight regain after lifestyle intervention alone . There is also evidence that Wegovy treatment is effective at 2 years, but further research is urgently needed.

Prioritising prevention

While weight management drugs can help, preventing obesity requires a comprehensive societal effort. Healthcare systems must proactively detect and address early signs of weight gain. However, the responsibility extends beyond healthcare providers. Governments play a crucial role by regulating the food and drinks industry, implementing policies to ensure access to affordable and nutritious food. This includes restricting unhealthy food marketing, especially to children, and mandating clear nutritional labelling. Governments should also invest in creating public spaces that encourage physical activity, such as cycle-friendly cities and green spaces. A whole society approach is vital. Collaboration across sectors—education, transportation, agriculture, media, and especially the food and drinks industry—is necessary to create a supportive environment for healthy living. Without such efforts, obesity will continue to burden society and healthcare systems. By working together, we can make healthy choices accessible and prioritize a healthier future for all.

Researchers at the Centre for Global Chronic Conditions at LSHTM recently worked on the CO-CREATE project to understand how different societal factors, stakeholders and institutions associated with obesity interact at various levels, and the implications these have on policy, especially for young people. The project has recently concluded and is in the process of assessing and promoting relevant policy actions and strategies for implementation. LSHTM researchers have also been involved in the PROMISE research programme to improve the assessment and management of obesity for children in the UK.