Four best weight-loss treatments

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Definitions of obesity and overweight

According to the World Health Organization, overweight and obesity are defined as: abnormal or excessive fat accumulation that presents a risk to health. A body mass index (BMI) >25kg/m2 is considered overweight, and >30kg/m2 is obese. The prevalence of obesity is reaching epidemic proportions, with more than four million people dying each year as a result of being overweight or obese in 2017 according to the global burden of disease.2 

The new guideline recommends that adults living with obesity or overweight with weight-related complications (eg type 2 diabetes, cardiovascular disease (CVD), stroke, non-alcoholic steatohepatitis, obstructive sleep apnoea, osteoarthritis, and certain types of cancer [eg colorectal cancer]), who do not respond to lifestyle interventions alone, should be treated with pharmacotherapy. Lifestyle interventions should be continued.1

The choice of pharmacotherapy depends on the patient’s clinical profile, preference, and needs of the patient, as well as comorbidities, costs, and access to the therapy.1

Key drivers of obesity and overweight

According to Boachie et al (2022), one of the key drivers of obesity and overweight is an obesogenic environment. This environment is characterised by the availability of unhealthy cheap foods, extensive marketing and a fast-food industry that is growing in heaps and bound.3

As a result of the easy availability, the consumption of ultra-processed foods and sugar-sweetened beverages has grown. Furthermore, individuals have become more sedentary.3

However, according to Lin and Li genetics, the essential causes of obesity remain somewhat controversial.  They propose that genetics, epigenetics, as well as the macro- (lifestyle factors) and the micro-environment contribute to obesity and overweight.4

Genetics predisposes an individual to become obese – for example, a child with one obese parent has a three-time risk to become obese as an adult, while when a child’s parents are both obese, this child has a 10-fold risk of future obesity.4

Several genetic, neuroendocrine, and chromosomal defects that can result in obesity include Prader-Willi Syndrome (a neurodevelopmental disorder with hypothalamic dysfunction, due to the deficiency of imprinted genes).4 

Endocrine disorders such as polycystic ovary syndrome can also lead to increased body fat. Chromosomal defects that can result in obesity, include deletion of 16p11.2, 2q37 (brachydactyly mental retardation syndrome), 1p36 (monosomy 1p36 syndrome), 9q34 (Kleefstra syndrome), 6q16 (PWS-like syndrome), 17p11.2 (Smith Magenis syndrome), and 11p13 (Wilms tumour, Aniridia, Genitourinary syndrome eg undescended testicles or hypospadias in males).4 

Epigenetic remodelling during early postnatal development and parental gametes has also been implicated and may explain the exponential increase in obesity over the past few decades, write Lin and Li.4

The environment and gut microbiota influence parental gametes. This may result in alterations to parental gametes, which in turn can be transmitted trans-generationally, predisposing children to the risk of obesity.4

In terms of the micro-environment, evidence shows that variations of gut microbiome cause alterations in an individual’s metabolism. For example, an animal model compared mice with normal gut microbiota, to germ-free male mice (without gut microflora). Germ-free mice had 42% less total body fat, even while consuming 29% more food a day.4   

Cost of treating patients living with obesity or overweight

As mentioned above, patients living with obesity or overweight are at high risk of complications. Treating these complications places an additional burden on healthcare systems. For example, it is estimated that medical costs associated with treating patients living with obesity are 30% higher compared to those with a normal BMI.4

According to Boachie et al, 23% and 27% of South African adults are overweight or obese, respectively. Health societies are predicting that these figures will increase by 10% increase among adults by 2030.3

The team performed an analysis of the total cost of treating patients living with obesity or overweight in South Africa. Their research shows that the cost of treating adults in the public healthcare sector amounted to more than R33m in 2020. This represented 15.38% of government’s healthcare expenditure and equates to 0.67% of the country’s gross domestic product.3

Boachie et al concluded that obesity and overweight impose a huge financial burden on the public healthcare system in South Africa. The team called for urgent preventative, population-level interventions to reduce overweight and obesity rates. A reduction in overweight and obesity levels in the country will reduce the incidence, prevalence, and overall healthcare spending on comorbidities.3

Nine weight-loss recommendations from the AGA

The AGA guideline recommends:

  1. Long-term (>52-weeks) pharmacotherapy and lifestyle interventions for patients with a BMI >30kg/m2, or >27kg/m2 with weight-related complications. Suggested lifestyle interventions include hypocaloric diets (500kcal/d–600kcal/d deficit) combined with at least 150 minutes of physical activity per week.
  2. Based on its benefit profile, semaglutide 2.4mg may be prioritised over other approved anti-obesity medications (AOMs) for the long-term treatment of obesity for most patients.
  3. Liraglutide 3mg is a glucagonlike peptide1 receptor agonists (GLP-1RAs), approved for the treatment of obesity in South Africa. The AGA cautions that GLP-1RAs may delay gastric emptying with adverse effects of nausea and vomiting. These side effects may be overcome by gradually titrating the dose. GLP-1 RAs have been associated with increased risk of pancreatitis and gallbladder disease.
  4. Phentermine-topiramate is effective for treating migraine headaches and may therefore be preferred in patients with comorbid migraines. Phentermine-topiramate ER should be avoided in patients with a history of CVD and uncontrolled hypertension. Furthermore, topiramate is teratogenic.
  5. Naltrexone-bupropion may be considered for the treatment of overweight or obesity in patients who are attempting smoking cessation, and in patients with depression. Naltrexone-bupropion ER should be avoided in patients with seizure disorders and used with caution in patients at risk of seizures and not used concomitantly with opiate medications. Blood pressure and heart rate should be monitored periodically while taking naltrexone-bupropion ER, especially in the first 12 weeks of treatment.
  6. Do not use orlistat. However, some patients who want to lose a small amount of weight may prefer to use orlistat due to its low risk of gastrointestinal side effects. Patients using orlistat should take a multivitamin daily. Vitamins should contain fat-soluble vitamins (A, D, E, K) and should be taken two hours apart from orlistat.
  7. Phentermine monotherapy is approved for short-term use (12 weeks). Phentermine should be avoided in patients with a history of CVD. Blood pressure and heart rate should be monitored periodically.
  8. Diethylpropion monotherapy is approved for short-term use (12 weeks). Diethylpropion should be avoided in patients with a history of CVD. Blood pressure and heart rate should be monitored periodically.

Can we slow down the obesity pandemic?

In an editorial published in the International Journal of Public Health, Prof Harry Rutter,  senior academic adviser to Public Health England, writes: “I was asked recently to name the single most important intervention to reduce childhood obesity. My weary reply was that the single most important intervention is to understand that there is no single most important intervention”.5

He adds that the key to understanding obesity is to pursue a shift in paradigm – from traditional approaches to applying objective scientific analysis, recognising that it is a complex disease requiring a multidisciplinary approach.5

Apart from lifestyle modification and pharmacotherapy, a multidisciplinary, individualised approach should also include weight-loss behavioural therapy, and if patients have comorbid depression, and eating disorders, or if they lack motivation, a psychiatrist should also be involved in care.6

A typical weight-loss behavioural programme consists of weekly sessions lasting between 60–90 minutes for at least six months followed by maintenance gatherings every other week through another 12 months to prevent weight regain.6

Weight-loss behavioural programmes are aimed at teaching patients to:

  • Monitor their eating: slow down decision-making, allowing them to make healthier choices
  • Stimulus control: reorganise their environment in order to lessen the cues for inappropriate food consumption and increase those for appropriate diet or physical activity
  • Behavioural substitution: recognise non-hunger cues to snack and replace eating with different behaviours
  • Problem-solving: identify a problem that hinders their weight-loss, contemplate outcomes associated with different choices, choose the healthiest, implement a specific plan, assess the success of the selected solution 
  • Cognitive restructuring: identifies and modifies maladaptive thoughts that promote overeating and lack of exercise
  • Cognitive behavioural therapy: focuses on altering the cognitive and behaviouralmechanisms that causes the problem behaviour, and utilise cognitive and behaviouralstrategies to make positive changes
  • Relapse prevention: prepare and plan for relapse prevention includes educating them to foresee challenging situations that could result in overeating, and to utilise strategies to overcome such intervals.

Boachie et al recommend the following preventative population-level interventions:3

  • Sugar tax: can reduce consumption of sugary drinks among adults.
  • Subsidies for healthy foods.
  • Restrictions on marketing and advertising (including labelling): will help reduce consumption of unhealthy foods and sugary drinks
  • Campaigns that inculcate healthy eating norms among school children: These long-term interventions have been shown to lead to significant BMI reductions and can avoid up to 2.4 million cases of diabetes, 1.4 to 1.7 million CVDs, and 73 000–127 000 cases of cancer. Broad population level measures to prevent CVD and endocrine diseases should be prioritised.


  1. Grunvald E, Shah R, Hernaez R, et al. AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity. Gastroenterology, 2022.
  2. World Health Organization. Obesity.
  3. Boachie MK, Thsehla E, Immurana M, et al. Estimating the healthcare cost of overweight and obesity in South Africa. Global Health Action, 2022.
  4. Lin X, Li H. Obesity: Epidemiology, Pathophysiology, and Therapeutics. Front Endocrinol (Lausanne), 2021.
  5. Rutter, H. The single most important intervention to tackle obesity. Int J Public Health, 2012.
  6. Elhag W, Ansari WE (2022). Medical Weight Management: A Multidisciplinary Approach. In (Ed.), Weight Management - Challenges and Opportunities [Working Title]. IntechOpen.

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