The World Health Organization (WHO) defines obesity as: Abnormal or excessive fat accumulation that presents a risk to health. A body mass index (BMI) >25 is considered overweight, and >30 is obese.²

Global data for 2021 indicate that 13% of adults are obese and 39% are overweight. Furthermore, one in five children and adolescents are considered overweight.³

For children, age needs to be considered when defining overweight and obesity. For children >5-years of age:⁴

• Overweight is weight-for-height >2 standard deviations above WHO Child Growth Standards median
• Obesity is weight-for-height >3 standard deviations above the WHO Child Growth Standards median.

The vast majority of overweight or obese children live in developing countries, where the rate of increase has been more than 30% higher than that of developed countries.²

In children and adolescents (between 5- to 19-years), overweight and obesity are defined as:⁴

• Overweight is BMI-for-age >1 standard deviation above the WHO Growth Reference median
• Obesity is >2 standard deviations above the WHO Growth Reference median.

Complications associated with obesity

Complications of obesity, which is classified as a disease by major healthcare bodies, include metabolic (diabetes, hypertension, and non-alcoholic steatohepatitis), mechanical (obstructive sleep apnoea and orthopaedic problems), and mental health complications (anxiety and depression), as well as others such as cardiovascular disease and certain cancers. Many of these comorbidities are associated with a high risk of morbidity and mortality.¹

Preventive strategies alone not successful

Weight-loss of 5%-10% of body mass has been shown to reduce obesity-related complications and improve quality of life. However, preventive strategies alone have had little success.¹

The use of pharmacotherapy to promote and maintain weight loss dates back to the 1930s, but many have been associated with serious adverse events, which have led to their withdrawal. Adverse events associated with early pharmacological agents to support weight-loss include serious cardiotoxicity, psychiatric disturbances, and dependency.¹

Subsequently, newer, and safer agents have been developed such as liraglutide 3mg, the only glucagon-like peptide 1 receptor agonist (GLP-1RA) approved for weight management in both adults and adolescents in South Africa. Liraglutide was officially launched in South Africa on 6 February 2021.⁵

Liraglutide was approved in 2014 by the American Food and Drug Administration (FDA) as an adjunct to a reduced calorie diet and greater physical activity for adults for chronic weight management in adult patients with obesity or who are overweight with a BMI >30 kg/m2 or a BMI of >27 kg/m2 or who have at least one weight-related condition.⁶

In 2020, the FDA approved liraglutide 3mg for chronic weight management among paediatric patients aged >12-years who are obese, as defined by specific BMI cut-offs for age and sex that correspond to a BMI >30 kg/m2 or higher for adults, and who weigh more than 60 kg.⁶

The efficacy and safety of liraglutide 3mg in the management of obesity has been shown in numerous studies.^7,8,9,10

Astrup et al (2009) compared four different dosages of liraglutide 1.2mg, 1.8mg, 2.4mg and 3mg) in 564 patients (18-65 years of age, BMI 30-40kg/m2). Participants were randomised to one of the four dosages, placebo, or orlistat (120mg). All individuals had a 500 kcal per day energy-deficit diet and increased their physical activity throughout the trial.⁷

Liraglutide was administered subcutaneously once daily. For the purposes of this article, only the results of the 3mg dosage will be reported. Participants in the liraglutide 3mg group lost a mean of 7.2kg compared to 4.1kg in the orlistat and 2.8 in the placebo group over the study period.⁷

Furthermore, more individuals (76%) treated with liraglutide 3mg lost more than 5% baseline weight than those treated with orlistat (44%). The proportion of people losing more than 10% of baseline weight was greater with liraglutide 3mg (28%) than with placebo (2%).⁷

Weight loss was accompanied by reductions in waist circumference, systolic and diastolic blood pressure, and frequency of both metabolic syndrome and prediabetes. Liraglutide was generally well tolerated. However, nausea and vomiting were more frequent with liraglutide than with the other treatments, although these events were mostly transient and of mild or moderate intensity.⁷

A study by Wadden et al (2013) showed similar results. From randomisation to week 56, weight decreased an additional mean 6.2% with liraglutide 3mg and 0.2% with placebo.⁸

More participants receiving liraglutide (81.4%) maintained the ≥5% run-in weight loss, compared with those receiving placebo (48.9%), and 50.5% versus 21.8% of participants lost ≥5% of randomisation weight. Liraglutide produced small but statistically significant improvements in several cardiometabolic risk factors compared with placebo.⁸

Pi-Sunyer et al (2015) conducted a 56-week, double-blind trial involving 3731 participants who did not have type 2 diabetes and (T2DM) who had a BMI of at least 30kg/m2 or a BMI of at least 27kg/m2 if they had treated or untreated dyslipidaemia or hypertension. Participants were randomised to liraglutide 3mg (n=2487 patients) or placebo (n=1244 patients). Both groups received counselling on lifestyle modification.⁹

At week 56, participants in the liraglutide group had lost a mean of 8.4±7.3kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg. A total of 63.2% of the participants in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight, and 33.1% and 10.6%, respectively, lost more than 10% of their body weight.⁹

Davies et al (2015) investigated efficacy and safety of liraglutide vs placebo for weight management in adults participants with overweight or obesity and T2DM. Participants were randomised to once-daily, subcutaneous liraglutide 3mg (n=423), liraglutide (1.8 mg) (n=211), or placebo (n=212), all as adjunct to 500 kcal/day dietary deficit and increased physical activity (≥150 min/week).¹⁰

Weight loss was 6% (6.4 kg) with liraglutide 3mg compared to 2% (2.2kg) with placebo. Weight loss of ≥5% occurred in 54.3% with liraglutide 3mg versus 21.4% with placebo. Weight loss >10% occurred in 25.2% with liraglutide 3mg versus 6.7% with placebo.¹⁰

Conclusions

In Southern Africa, overweight increased by 8.3% between 1990 and 2019 (31.4%-39.7%) (38.7–40.7 in 2019) in women and by 8.5% in men (20.2%-28.7% for the same period.¹¹

Obesity increased by about >1.5-fold from 12% to 18.5% in women, while in men, it nearly doubled from 4.5% to 8.8%. In children, obesity more than doubled while overweight increased by 27.4% and 37.4% in girls and boys, respectively.¹¹

In 2019, women from South Africa (44.7%), Swaziland (33.9%) and Lesotho (31.6%) had the highest prevalence of obesity and overweight (71.3%, 59.6%, 62.3%, respectively). Similar patterns were recorded in men in these countries.¹¹

Age-standardised mortality attributed to high BMI increased by 1.15% annually for men from 57.3 in 1990 to 80.0 in 2019. Among men, six countries (Mauritius, Lesotho, Botswana, Namibia, South Africa, and Swaziland) had mortality rates exceeding 100 per 100 000 in 2019. Among females, seven countries (Botswana, Lesotho, Mauritius, Namibia, South Africa, Swaziland, and Zimbabwe) had mortality rates exceeding 100 per 100 000) in 2019.¹¹

Gona et al caution that we ‘have a window of opportunity to halt and reverse the negative health outcomes associated with obesity before they become endemic and out of control’.¹¹

REFERENCES:

1. O’Neil PM, Birkenfeld AL, McGowan B, et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blid, placebo and active controlled, dose-ranging, phase 2 trial. The Lancet, 2018.
2. WHO. Obesity. https://www.who.int/health-topics/obesity#tab=tab_1
3. Ritchie H and Roser M (2017). "Obesity". Published online at OurWorldInData.org. Retrieved from: 'https://ourworldindata.org/obesity' [Online Resource]
4. WHO. Obesity and overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
5. Novo Nordisk. Liraglutide South Africa launch, 6 February 2021.
6. US Food and Drug Administration (2020). FDA approves weight management drug for patients aged 12 and older. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-weight-management-drug-patients-aged-12-and-older
7. Astrup A, Rossner S, Van Gaal L, et al. Effects of liraglutide in the treatment of obesity: a randomised, double‐blind, placebo‐controlled study. Lancet, 2009.
8. Wadden TA, Hollander P, Klein S, et al. Weight maintenance and additional weight loss with liraglutide after low‐calorie‐diet‐induced weight loss: the SCALE Maintenance randomized study. Int J Obes (Lond), 2013.
9. Pi‐Sunyer X, Astrup A, Fujioka K, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med, 2015.
10. Davies MJ, Bergenstal R, Bode B, et al. Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial. JAMA, 2015.
11. Gona PN, Kimokoti RW, Gona CM, et al. Changes in body mass index, obesity, and overweight in Southern Africa development countries, 1990 to 2019: Findings from the Global Burden of Disease, Injuries, and Risk Factors Study. Obesity Science and Practice, 2021.
12. Ward ZJ, Bleich SN, Cradock AL, et al. Projected U.S. State-Level Prevalence of Adult Obesity and Severe Obesity. NEJM, 2019.