Dr Lydia Altini MBBCh DipIBLM

In early November, the first-ever South African clinical practice guideline for treating adult obesity was published in a Special Issue of the South African Medical Journal (SAMJ).¹ With obesity now a global epidemic driving major health, social, and economic consequences, this guideline arrives at a critical moment. It provides long-overdue, evidence-based direction for healthcare providers and represents an essential step toward addressing a public health crisis that demands urgent action.

In South Africa, 28% of adults were living with obesity in 2017, with a significantly higher prevalence in women than men (42.6% vs 12.1%). A further 24% of adults are overweight, and rates among children and adolescents are also concerningly high.¹

Obesity is now recognised as a chronic, relapsing disease influenced by genetic, primary and secondary factors. Clinically, it is defined as a body mass index (BMI) above 30, though waist circumference is an important complementary measure and better predictor of cardiometabolic risk. Weight-related diseases, including type 2 diabetes, hypertension, stroke and cardiovascular disease, are now leading contributors to morbidity and mortality in South Africa, driving enormous health-system costs. Excess weight is also associated with cancer, mental illness, sleep disorders, metabolic liver and kidney disease, and poor pregnancy outcomes. ²

Although many theories exist, no single model fully explains how body weight is regulated. What we do know is that modern diets and environmental exposures disrupt appetite and weight-control systems, particularly in those who are genetically vulnerable. Importantly, in primary obesity, “the path into obesity differs from the path out”: the drivers of weight gain are easier to prevent than to reverse.³ Prevention must therefore remain a public health priority. But for those already living with obesity, effective treatment requires targeted support that addresses both the underlying biology, especially increased appetite, and modifiable factors such as diet, physical activity, stress, and sleep.³

Incretin Therapies: A Major Therapeutic Advance

GLP-1 receptor agonists (GLP-1 RAs) and newer dual and triple incretin therapies represent a major breakthrough in obesity management. They address both increased appetite and the body’s counter-regulatory mechanisms that drive weight regain after weight loss.

These medications bridge the gap between lifestyle intervention alone and metabolic bariatric surgery, achieving approximately 15–20% total body weight loss in clinical trials. ⁴ The World Health Organisation recently endorsed the use of weight-loss medications for adults with obesity for the first time.⁵

Although currently out of reach for most South Africans, GLP-1 therapies are available through private pharmacies with a prescription. Access is likely to expand as more options become available, including drugs with differing mechanisms of action, varied dosing schedules, and more favourable cost profiles such as the new oral GLP-1 RAs.

However, the rapid uptake of these medications raises important clinical questions regarding informed choice, treatment optimisation, and long-term safety.

Incretin therapies have known adverse effects, a high rate of weight regain upon discontinuation, and may require lifelong use for sustained benefit. ⁴

Real-world data reported at Obesity Week 2025 (retrospective cohort, >1.2 million patients) showed:

• Nearly 60% of people who discontinue GLP-1 therapy regain at least some of the weight within one year.
• Only 38% remain adherent at 12 months.
• Average weight loss at discontinuation was 10.1%, and those who lost the most weight regained the most. ⁶

These findings highlight the need for personalised, long-term strategies that combine pharmacotherapy with lifestyle medicine to optimise outcomes. In fact, in clinical trials where patients received both GLP-1 therapy and structured lifestyle advice, they achieved greater weight loss, better adherence and were more likely to sustain weight loss after discontinuation of therapy compared to those receiving medication alone. ⁷

Understanding GLP-1 Receptor Agonists

GLP-1 RAs (liraglutide, semaglutide), dual GLP-1/GIP agonists (tirzepatide), and investigational triple agonists mimic endogenous hormones that regulate appetite, satiety and glucose metabolism. ⁸ They affect both central and peripheral pathways by:

• Enhancing insulin secretion
• Improving insulin sensitivity
• Inhibiting glucagon
• Delaying gastric emptying
• Suppressing appetite
• Reducing cravings—including for sugary, fatty foods and even alcohol

Cardiometabolic benefits extend beyond weight loss, improving metabolic liver disease, reducing major cardiovascular events, and lowering cardiovascular mortality. ⁹

Risks and Adverse Effects

Although generally well-tolerated, GLP-1 RAs are associated with nausea, vomiting, constipation, gastroesophageal reflux and abdominal pain. These side effects may lead to early discontinuation (over 30% stop within the first month). ⁴

Additional concerns include:

• Micronutrient deficiencies (22.4% prevalence within 1 year of starting GLP-1 RAs) including iron, B12, folate, vitamin D, calcium, magnesium and zinc ¹⁰
• Lean mass loss of up to 38% of total weight lost ¹⁰
  • Greater muscle loss in men
  • Greater bone loss in older adults and postmenopausal women
• Psychosocial factors: stigma, emotional eating, unrealistic expectations, weight cycling

These risks significantly increase the importance of concurrent lifestyle interventions.

Lifestyle Interventions: The Foundation of Safe and Effective Therapy

(Mozaffarian et al, 2025)

Four major organisations in lifestyle medicine, obesity medicine and nutrition, recently released a joint clinical advisory, Nutritional Priorities to Support GLP-1 Therapy for Obesity – highly recommended reading for any healthcare provider prescribing GLP-1 RAs. It outlines key nutritional and behavioural strategies required to maximise efficacy and safety. ¹¹

1. Patient-Centred Initiation

• Begin with personalised health and weight goals.
• Tailor decisions to patient preferences and readiness to change.
• Consider financial constraints, food security, and health literacy since these impact adherence and equity.

2. Comprehensive Baseline Assessment

Include:

• Dietary patterns and emotional triggers
• Disordered eating behaviours
• Muscle strength and function
• Body composition
• Sleep, stress, substance use
• Mental health and social support

This ensures early identification of risk factors for muscle loss, malnutrition, and poor adherence.

3. Nutrition and Lifestyle During Therapy

• Manage GI side effects with dose titration, small frequent meals, and bland foods.
• Prioritise nutrient-dense, minimally processed foods to prevent deficiencies.
• Emphasise adequate protein intake, especially for older adults or postmenopausal women.
• Implement resistance training and regular aerobic exercise to preserve muscle and bone.
• Support patients through altered food preferences and prevent overly restrictive eating.

4. Ongoing Support and Multidisciplinary Care

• Use group visits, telehealth, digital platforms and dietitian support to enhance adherence.
• Help patients navigate food insecurity.
• Encourage sleep optimisation, stress management, and strong social connections.

5. Addressing Health Equity

In South Africa, inequities in access to medication, nutritious food and allied health support remain substantial. Improving access to culturally appropriate dietary guidance and addressing food insecurity are essential for equitable care.

Key Recommendations

• Prioritise sustained weight loss of at least 3–5%, as even modest reductions significantly improve metabolic health.
• Prioritise diets that reduce overall caloric intake, favouring nutrient-rich foods over ultra-processed foods.
• Provide comprehensive lifestyle interventions for at least six months.
• Monitor for nutrient deficiencies and ensure adequate protein to preserve lean mass and bone health.
• Encourage multidisciplinary collaboration among clinicians, dietitians, psychologists, and community-based resources.

Conclusion: GLP-1 RAs Open the Door – Lifestyle Medicine Keeps It Open

GLP-1 receptor agonists are powerful tools, but not magic bullets. Their full potential is only realised when they are integrated into a comprehensive Lifestyle Medicine framework that supports nutrition, movement, sleep, stress management, mental wellbeing, and strong social connections.

For South African healthcare providers, the goal is clear:
Use evidence-based pharmacotherapy as an adjunct to personalised lifestyle interventions to achieve meaningful, long-lasting health outcomes. This is the path to improved metabolic health, well beyond medication alone.

References:

1. Goedecke J, Hellig J, Conradie-Smit M, et al. Epidemiology of Adult Obesity. S Afr Med J. 2025. e3616. 10.7196/SAMJ.2025.v115i9b.3616. https://doi.org/10.7196/SAMJ.2025.v115i9b.3616
2. Chandiwana N, Venter W, Manne-Goehler J, et al. Obesity is South Africa’s new HIV epidemic. S Afr Med J. 2024;114(3): e1927. Published 2024 Mar 18. doi:10.7196/SAMJ. 2024.v114i3.1927 https://doi.org/10.7196/SAMJ.2024.v114i3.1927

3. May W, Goedecke J, Conradie-Smit M. The Science of Obesity. S Afr Med J. e3600. 10.7196/SAMJ.2025.v115i9b.3600. https://doi.org/10.7196/SAMJ.2025.v115i9b.3600

4. Koball AM, Ames GE, Grothe KB, Clark MM, Collazo-Clavell ML, Elli EF. Decoding Obesity Management Medications and the Journey to Informed Treatment Choices for Patients. Mayo Clin Proc. 2025 Jan;100(1):111-123. doi: 10.1016/j.mayocp.2024.10.003. Epub 2024 Dec 5. PMID: 39641717.1016/j.mayocp.2024.10.003
5. Rigby, J. WHO backs weight-loss drugs for obesity and urges change in Mindset | reuters, Reuters.com. 2025. https://www.reuters.com/business/healthcare-pharmaceuticals/who-backs-weight-loss-drugs-obesity-urges-change-mindset-2025-09-15/ (Accessed: 27 November 2025).

6. Tucker M. Over Half Regain Weight After Stopping GLP-1s. Medscape November 13, 2025. https://www.medscape.com/viewarticle/over-half-regain-weight-after-stopping-glp-1s-2025a1000vmt (Accessed 18 November 2025)

8. Wadden TA, Chao AM, Machineni S, et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nat Med. 2023;29(11):2909-2918. doi:10.1038/s41591-023-02597-w
   Guo H, Yang J, Huang J, et al. Comparative efficacy and safety of GLP-1 receptor agonists for weight reduction: A model-based meta-analysis of placebo-controlled trials. Obes Pillars. 2025; 13:100162. Published 2025 Jan 30. doi: 10.1016/j.obpill.2025.100162 1016/j.obpill.2025.100162
9. Alfaris N, Waldrop S, Johnson V, Boaventura B, Kendrick K, Stanford FC. GLP-1 single, dual, and triple receptor agonists for treating type 2 diabetes and obesity: a narrative review. EClinicalMedicine. 2024; 75:102782. Published 2024 Aug 30. doi: 10.1016/j.eclinm.2024.102782 1016/j.eclinm.2024.102782
10. Scott Butsch W, Sulo S, Chang AT, et al. Nutritional deficiencies and muscle loss in adults with type 2 diabetes using GLP-1 receptor agonists: A retrospective observational study. Obes Pillars. 2025; 15:100186. Published 2025 Jun 10. doi: 10.1016/j.obpill.2025.100186 1016/j.obpill.2025.100186
11. Mozaffarian D, Agarwal M, Aggarwal M, et al. Nutritional priorities to support GLP-1 therapy for obesity: A joint advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and the Obesity Society. Obes Pillars. 2025;15:100181. Published 2025 Jun 3. doi:10.1016/j.obpill.2025.100181 1002/oby.24336

Photo Credit: Photo by Joachim Schnürle on Unsplash