The Rise of Appetite Suppressants
In the past decade the medical community has witnessed a surge in medications originally designed for type 2 diabetes that are now being promoted for weight loss. Semaglutide (brand names Ozempic and Wegovy) and terpenatide (Mounjaro) have each demonstrated rapid weight loss in clinical trials, attracting attention from celebrities, influencers and the general public. The appeal is understandable: a single injection that can deliver 10–20 kilograms of body‑weight reduction in a matter of months. Yet the clinical experience shows a more complex picture.
When I first began investigating these agents, the focus was strictly on glycaemic control. Over time, the evidence accumulated that the drugs shape appetite, slow gastric emptying and alter the brain’s reward circuitry. This multidisciplinary approach—endocrinology, neuroscience and nutrition—provides the framework that informs how we must now position these drugs in the treatment pathway for metabolic disease.
How Fat Accumulates in the Modern Body
The Natural Energy Storage System
Our bodies have evolved to store excess caloric energy as fat. This strategy, indispensable for survival during periods of scarcity, has been repurposed by contemporary food systems. Every carbohydrate consumed can be converted to fat if not needed for immediate energy, and processed foods are engineered to maximise palatability and caloric density. Over several decades, a small, sustained intake of excess calories leads to a ‘dual‑store’ system:
- Subcutaneous fat: generally harmless and used in emergencies.
- Visceral and organ fat: associated with insulin resistance, type 2 diabetes and cardiovascular disease.
Once the subcutaneous depot is saturated, the surplus is diverted to the liver and other visceral sites, setting the stage for metabolic derangements.
The Genetic Gamble of Appetite
Unlike other physiological pegs, appetite is regulated by a large array of genes. Leptin, a hormone produced by adipose tissue, was identified in the 1990s as a key satiety signal. However, leptin deficiency is rare, and the majority of obesity cases arise from multiple genetic variants that interact with environmental triggers. A person’s ‘genetic luck of the draw’ therefore shapes their baseline food drive. For most individuals, appetite is a flexible state that responds to the brain’s reward circuitry, hormonal feedback and, importantly, the external food environment. This is why a bubble of highly processed, calorie‑dense foods can inflate the appetite of a genetically predisposed individual to a pathological degree.
Clinical Impact of Semaglutide and Terpenatide
Both semaglutide and terpenatide act on the glucagon‑like peptide‑1 (GLP‑1) receptor, but terpenatide additionally engages the glucose‑dependent insulinotropic polypeptide (GIP) receptor. The combined action produces a more potent appetite suppressive effect and a faster delay of gastric emptying, which together explain the superior weight loss seen in trials. Two key data points are often cited:
- Semaglutide 2.4 mg weekly leads to an average loss of 10–15 kg over 68 weeks.
- Terpenatide 5 mg weekly produces an average loss of 15–20 kg within 36 weeks.
However, observational studies indicate a 30–40 % reduction in weight loss compared with controlled trials. Side effects—particularly nausea and vomiting—result in roughly half the participants discontinuing treatment within the first twelve months. In a real‑world setting, the average weight loss is therefore closer to 60–70 % of the clinical trial figure.
Practical Guidance for Healthcare Providers
Below are evidence‑based steps for integrating these agents into patient care:
- Identify the right candidates: Patients with a BMI of 30+ kg/m², or those with a BMI of 27–29.9 kg/m² and at least one metabolic comorbidity (e.g., hypertension, dyslipidaemia).
- Set realistic expectations: Explain that weight loss is typically 10–20 kg but highly individual. Discuss the possibility of nausea and the common pattern of dose titration.
- Combine medication with lifestyle support: Even with pharmacological help, patients who invest in structured diet plans and physical activity maintain weight loss far better. A simple 8‑week liquid diet focusing on protein, non‑starchy vegetables and a low‑carbohydrate plan can accelerate initial satiety.
- Monitor for side effects: Schedule follow‑up visits at 4, 8 and 12 weeks to adjust dose or offer symptom‑management strategies.
- Plan for sustainability: After a maximum of twelve months, taper the drug while reinforcing behavioural strategies that prevent rebound weight gain.
The Economics of Medication Versus Lifestyle Change
The NHS pays approximately £122 per month for terpenatide and a similar fee for semaglutide. In isolation, the cost per kilogram of weight loss translates into a high incremental cost‑effectiveness ratio, especially when the therapeutic effect is limited to a single year. By contrast, lifestyle programmes with measurable reductions in BMI can cost a fraction of this amount over the long term because the benefit persists while the drug is stopped.
Research from the Newcastle Magnetic Resonance Centre confirms that a 15 kg weight loss, even when achieved through diet alone, can normalize liver fat, improve insulin sensitivity and reverse the reduced pancreatic volume seen in type 2 diabetes. In fact, the programme’s success rate is higher for patients who achieve the weight loss target and maintain it across the subsequent months.
Integrating Medication with Lifestyle: A Dual Strategy
Pharmacological appetite suppressants are not stand‑alone solutions. The best outcomes rise when drugs coexist with:
- Structured dietary education—learning to read labels, portion controlling and nutrition planning.
- Regular physical activity tailored to the patient’s capacity and interests.
- Behavioural therapy—including goal setting, self‑monitoring and relapse prevention.
- Peer support groups, whether virtual or in person, which lend accountability and shared learning experiences.
When patients can apply the science of appetite regulation to their everyday food choices, they are more likely to keep the weight off after the medication is withdrawn.
New Research from Newcastle and the Path Forward
Our long‑standing work with the twin‑cycle hypothesis continues to yield actionable insights. One key finding is that early intervention—well before the accumulation of liver fat—provides the best chance of achieving and sustaining remission of type 2 diabetes. The NHS Type 2 Diabetes Path to Remission programme now uses these principles to coach patients through a 12‑week diet without pharmacological support, resulting in an average weight loss of 10.3 kg and a one‑third remission rate.
Furthermore, we are evaluating whether combining a structured diet with a short course of terpenatide could deliver the rapid weight loss of the drug while cementing new eating habits. Early data suggest that the combined approach outperforms diet alone and reduces the tendency to regain weight after the drug stops.
Conclusion
Appetite‑suppressing injections deliver tangible weight loss and improved glycaemic control, but they are not a silver bullet. They must be deployed thoughtfully: targeting patients who will benefit most, integrating them with robust dietary and lifestyle support, and planning for long‑term maintenance once the medication ends. By combining the precision of pharmacology with the discipline of behaviour change, we can offer patients a clearer path to reversing metabolic disease.
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