Health Systems Action

The New ‘Weight Loss’ Drugs – a Panacea?

A Heavyweight Problem

The world faces a growing epidemic of obesity, diabetes, cardiovascular disease, stroke and dementia, a complicated web of interconnected health issues that drastically reduce quality and length of life. Metabolic syndrome, the combination of high blood pressure, elevated blood sugar, excess body fat, and abnormal lipid profile affects approximately 25% of the global adult population, and over 650 million adults are obese.

The Cost

In the US alone, the direct and indirect costs of diabetes are estimated at over $327 billion annually, and the cost of obesity is also huge, around $147 billion per year. These figures include medical expenses and lost productivity, but do not account for pain and suffering of patients and families.

Market Size

The market for effective solutions is therefore substantial. Global sales of diabetes drugs are expected to reach over $80 billion by 2026. GLP-1 (Glucagon-Like Peptide-1) agonist (GLP-1a) drugs such as semaglutide (Ozempic) are the most promising new market entrants.

Failure of Previous Weight Loss Drugs

 Other weight loss drugs such as fen-phen and sibutramine were marked by failure due to dangerous side effects, minimal effectiveness, and issues with addiction and abuse that resulted in recalls and damaged trust. GLP-1a drugs are much safer. Nausea and vomiting are the only common side effects; pancreatitis and thyroid tumors are rare possible adverse effects.

A Shift in Focus for Diabetes Drugs

For decades, the assessment of diabetes drug efficacy was based on glucose control. In 2008 the United States FDA changed the rules: to obtain market approval pharmaceutical companies were required to demonstrate that their new agents could produce meaningful clinical benefits. Novel drug classes such as SGLT-2 inhibitors, for example, were shown to have beneficial impact on cardiovascular and renal (kidney) outcomes.

New Insights into Metabolism, Glucose Control and the Gut-Brain Connection

GLP-1a drugs emerged from 20 or more years of research. Scientists discovered that GLP-1, a hormone secreted in the gut, plays an important role in the regulation of blood glucose levels by enhancing insulin secretion and slowing gut emptying. Recent studies suggest that GLP-1a drugs also suppress cravings for alcohol and food; these effects in combination account for dramatic weight loss  – 15 % or more of body weight – that many patients experience. Recent insights reveal broader cardiovascular protection and even quality of life benefits.

Potential Benefits

GLP-1 agonists are now shown not only control glucose and induce weight loss but to protect the heart, blood vessels and kidneys. The newest drugs like tirzepatide produce previously undreamed-of weight loss numbers, 20% or more in over half of recipients, together with improvement in cardiac and metabolic parameters. At the same time, they reduce cardiovascular risk in patients with and without diabetes. One recent study showed a 20% reduction in the risk of major adverse cardiovascular events in adults who were overweight or obese. Patients with obesity and heart failure had reduced symptoms of fatigue, shortness of breath, and swelling, and better quality of life with improvements in physical abilities and exercise function.

Huge Demand – and Shortages

GLP-1 agonist drugs are now in short supply due to complex manufacturing processes, patent issues, and global supply chain disruptions. They are complex molecules, often produced through recombinant DNA technology, a process requiring sophisticated facilities and skilled labor that is time-consuming and costly. The costs associated with clinical trials and regulatory compliance will however be dwarfed by anticipated drug company revenues.

 Relevance to Low and Middle-Income Countries

 These drugs represent new hope for hundreds of millions of patients worldwide and will be true “blockbusters” for pharmaceutical companies in the months and years ahead. They will also generate huge bills for national healthcare systems in the US and other wealthy countries. In SA, their cost, about R2,500 per month, makes them inaccessible to the majority of patients. Priced at $200/year they might be cost-saving in countries like SA and India. But public health systems may lack the healthcare infrastructure necessary to administer and appropriately monitor their use.

 Non-Medication Alternatives and Their Challenges

 Lifestyle interventions such as diet and exercise are the cornerstone of treatment of obesity and metabolic syndrome. Remission of diabetes through dietary change is possible in around half of all patients newly diagnosed (within 5 years or so) but both weight loss and remission are difficult to maintain long-term. Most patients struggle to achieve and sustain the change.

 GLP-1 agonists contribute to the medicalisation of health problems attributable to the low availability and affordability of healthy food. The drugs become a “quick fix”; society prefers pills over lifestyle changes. But the quick fix is not a once-off, permanent solution: when GLP-1 agonists are discontinued, patients regain two thirds of the weight that was lost.

 Conclusion

 GLP-1 agonist drugs represent a major advance in the treatment of metabolic syndrome, diabetes, and obesity but come with substantial costs and accessibility barriers and their remarkable efficacy diverts attention from underlying systemic causes of these global epidemics. As their use increases, a fight for more favourable pricing in LMICs is likely but ongoing evaluation will be critical to balance benefits against longer term unintended consequences, and to ensure responsible and ethical use .

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