Current obesity guidelines recommend lifestyle interventions to achieve sustained weight loss. Studies show that weight loss of between 3%-5% can lead to clinically significant health improvements, and a 5%–10% weight loss over six months, is recommended to achieve additional benefits.^1,2 

Although lifestyle interventions such as dieting - aimed at creating a negative energy balance - and physical activity can lead to weight loss for many, a substantial proportion of individuals struggle to not only lose weight, but to maintain weight-loss.¹ 

Inability to lose weight requires more than willpower 

The primary cause of obesity is consuming more energy than the body expends. However, growing evidence indicates that weight loss is also affected by other factors, including evolutionary, endocrine, and neurobiological influences. This suggests that the ability to lose weight and keep it off involves more than just willpower.^1,3,4,5,6   

Another important factor that has a significant impact on weight management is food cravings, defined as the intense desires for specific food. Dieting is often blamed for causing food cravings, which can be triggered by physiological (eg nutritional deprivation), psychological (eg the ironic effects of trying to suppress thoughts about food), cognitive (eg thinking about food) and emotional factors (eg desire to eat or changes in mood).^7,8  

Chocolate and other calorie-dense foods are the most craved, affecting dietary adherence and promoting weight gain. Dalton et al demonstrated that improved craving control correlates with greater weight loss, highlighting its importance in obesity management.^7,8 

Complexity of obesity management 

The bottom line is that obesity is a complex disease, the treatment of which is more than changes to diet and physical activity. For adults, current guidelines advocate the management of overweight and obesity as a chronic disease incorporating multi-component lifestyle interventions, which include dietary adjustments, physical activity regimens, strategies aimed at fostering sustained behavioural changes over six- to 12-months, pharmacotherapy and bariatric surgery.⁹  

Guidelines for children and adolescents emphasise the use of body mass index (BMI) percentiles or standardised BMI scores derived from various reference groups to assess overweight or obesity. For younger populations, initial treatment strategies predominantly focus on multi-component lifestyle interventions incorporating dietary modifications, physical activity promotion, and behavioural modifications as primary therapeutic measures.⁹ 

Pharmacotherapy such as anti-obesity medications (AOMs) are indicated for adults with a BMI ≥30kg/m2 or if ≥27kg/m2 in the presence of one or more co-morbidities. In cases where non-surgical interventions fail to yield significant results and the individual has a body mass index (BMI) of ≥35kg/m², guidelines suggest considering bariatric surgery as an option.^9,10  

AOMs should also be considered for individuals living with obesity or obesity-related comorbidities who struggle with weight loss through lifestyle modifications alone. While long-term weight maintenance is challenging, with 80% failing to sustain ≥10% weight loss after a year, combining pharmacotherapy with lifestyle modifications show better long-term results.² 

Can AOMs control eating behaviour? 

As discussed above, losing weight is more than just a matter of willpower. Studies have shown that appetite suppressants can help control eating behaviour such as food cravings, overeating, and body weight.¹¹  

Phentermine is one of the oldest and most prescribed appetite suppressants (approved in 1959). It functions as an adrenergic reuptake inhibitor, prompting peripheral tissues to secrete noradrenaline. This increase in noradrenaline stimulates β-adrenergic receptors in the hypothalamus, reducing food intake, and activates the sympathetic nervous system, thereby increasing resting energy expenditure and promoting weight loss.¹¹ 

Additionally, phentermine enhances serotonin (5-HT) effects by inhibiting monoamine oxidase and preventing 5-HT removal by the lungs. Unlike amphetamine, which shares a similar chemical structure, phentermine does not influence dopamine secretion and resorption, resulting in a significantly lower risk for abuse or misuse.¹¹  

In South Africa, phentermine is indicated as a short-term adjunct in a medically monitored comprehensive regimen of weight reduction, which may include exercise, dietary caloric/kilojoule restriction, and behaviour modification, for individuals living with obesity (BMI ≥30kg/m²) who have not achieved an adequate clinical response to an appropriate weight-reducing regimen alone. Treatment with phentermine can be initiated at a lower BMI in patients with other risk factors. Secondary organic causes of obesity should be excluded before prescribing.¹² 

How effective is phentermine 

A recent study by Song et al (2023) compared the efficacy of various AOMs in real-world practice over a six-month period, involving participants with a BMI of 35kg/m² to 50kg/m². A total of 64.4% of participants achieved a weight loss of ≥5% during the study.²  

A total of 87.3% of participants in the phentermine group achieved ≥5% weight loss, 67.7% for the phentermine/topiramate group, 58.1% for the liraglutide group, 50% for the orlistat group, and 35.3% for the naltrexone/bupropion group. The liraglutide group did not significantly differ from the phentermine group at any time point.² 

Regarding secondary outcomes, 30.2% of participants lost >10% of their baseline body weight after six months. Participants in the phentermine group again scored highest (56.4%), followed by the phentermine/topiramate group at 35.3%, the lorcaserin group at 33.3%, the orlistat group at 25%, the liraglutide group at 14.2%, and the naltrexone/bupropion group at 11.8%.² 

How effective is phentermine in addressing food cravings? 

 In a 12-week clinical trial involving participants with a BMI of 35 to 50 kg/m², Moldovan et al assessed the effects of phentermine combined with a meal replacement system and lifestyle counselling on weight loss and food cravings compared to the meal replacement system alone.¹³  

Results indicated that the phentermine group achieved a significant weight loss of 12.1% from baseline, while the placebo group lost 8.8%. Participants in the phentermine group experienced reduced cravings across all food categories, and in particular reduced cravings for fats and sugars.¹³  

The study further demonstrated a significant positive correlation between weight loss and decreases in total food cravings, cravings for sweets, and state food cravings.¹³ 

Conclusion 

Overweight and obesity are significant risk factors for CVD. Maintaining an optimal body weight through strategies that reduce or reverse body fat is essential for lowering these risks. 

While lifestyle interventions help many achieve weight loss, a significant number of individuals struggle not only to lose weight but also to maintain it. This challenge highlights that weight loss involves more than just willpower.  

Current guidelines recommend a comprehensive approach to obesity treatment, including lifestyle modifications, pharmacotherapy, and, in some cases, bariatric surgery. Among AOMs, phentermine is one of the most prescribed appetite suppressants.  

Recent studies support the efficacy of phentermine. A significant proportion of users achieve substantial weight loss, and the medication also helps reduce food cravings. Long-term studies suggest that phentermine is effective for weight loss without increasing CV risks, making it a viable option for obesity management. 

Overall, managing obesity is a multifaceted challenge that extends beyond willpower, and AOMs like phentermine can be valuable tools in a comprehensive treatment plan. 

References  

1. Rebello CJ, Greenway FL. Reward-Induced Eating: Therapeutic Approaches to Addressing Food Cravings. Adv Ther, 2016.   
2. Song JE, Ko HJ, Kim AS. Comparison of the Efficacy of Anti-Obesity Medications in Real-World Practice. Drug Design, Development and Therapy, 2023. 
3. Romieu I, Dossus L, Barquera S, et al. IARC working group on Energy Balance and Obesity. Energy balance and obesity: what are the main drivers? Cancer Causes Control, 2017. 
4. Sato W, Sawada R, Kubota Y, Toichi M, Fushiki T. Unconscious Affective Responses to Food. PLoS One, 2016.   
5. Ylli D, Sidhu S, Parikh T, et al. Endocrine Changes in Obesity. [Updated 2022 Sep 6]. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279053/  
6. Reents J, Pedersen A. Differences in Food Craving in Individuals with Obesity with and without Binge Eating Disorder. Front Psychol, 2021. 
7. Dalton M, Finlayson G, Walsh B, et al. Early improvement in food cravings are associated with long-term weight loss success in a large clinical sample. International Journal of Obesity, 2017. 
8. Meule A. The Psychology of Food Cravings: The Role of Food Deprivation. Curr Nutr Rep, 2020.   
9. Gaskin CJ, Cooper K, Stephens LD, et al. Clinical practice guidelines for the management of overweight and obesity published internationally: A scoping review. Obesity Reviews, 2024. 
10. Chakhtoura M, Haber R, Ghezzaw M, et al. Pharmacotherapy of obesity: an update on the available medications and drugs under investigation. EClinical Medicine. Part of The Lancet Discovery Series, 2023. 
11. Kim HO, Lee JA, Suh HW, et al. Postmarketing surveillance study of the efficacy and safety of phentermine in patients with obesity. Korean J Fam Med, 2013. 
12. Professional information. Duromine. 2022. [Internet]. Available at: https://inovapharma.co.za/wp-content/uploads/2022/01/Duromine-PI.pdf  
13. Moldovan CP, Weldon AJ, Daher NS, et al. Effects of a meal replacement system alone or in combination with phentermine on weight loss and food cravings. Obesity, 2016.