Anti-obesity medication

Anti-Obesity Medications: A Journey Through Time

Imagine a world where obesity was just another condition, treatable like any other illness. That’s the promise of anti-obesity medications, which have been around since the early 1900s but have faced many challenges along the way. These drugs are designed to tackle the root causes of weight gain by altering fundamental processes in our bodies—appetite and energy expenditure.

The Early Days: A Timeline of Weight Loss Drugs

From elixirs and purgatives in ancient times to modern GLP-1 receptor agonists, the history of weight loss medications is a fascinating journey. Soranus of Ephesus’ remedies from the 2nd century AD were some of the earliest attempts at managing obesity. Fast forward to the early 20th century, where thyroid hormone treatments and amphetamines became popular but came with their own set of risks.

GLP-1 Receptor Agonists: The Modern Era

The 2020s saw a resurgence in GLP-1 receptor agonists like liraglutide, naltrexone/bupropion, orlistat, semaglutide, and tirzepatide. These drugs work by reducing appetite through serotonin receptors, increasing energy expenditure via beta-2 adrenergic receptors, and acting on neurotransmitters such as serotonin, dopamine, and norepinephrine.

Other mechanisms include altering glucagon and leptin signaling, inhibiting myostatin, and redirecting nutrients from adipose to lean tissue. Medications that reduce energy intake include GLP-1 agonists, 5-HT2C receptor agonists, and amylin analogues. Those that increase energy expenditure are adrenergic agonists, thyroid hormones, and fibroblast growth factor-21 receptor agonists.

Orlistat: A Breakthrough in Weight Loss

One of the most well-known medications is Orlistat (Xenical), which works by inhibiting pancreatic lipase. This enzyme breaks down triglycerides in the intestine, preventing them from being absorbed. The result? Increased lean mass and decreased fat mass in obese humans.

However, Orlistat can cause oily bowel movements, a side effect known as steatorrhea. In 2010, the FDA added new safety information about rare cases of liver injury to its label. Cetilistat, another drug that inhibits pancreatic lipase, was found to significantly reduce weight and was better tolerated than Orlistat in a 2010 trial.

SGLT2 Inhibitors: A New Approach

Another class of drugs, SGLT2 inhibitors, causes the loss of glucose in the urine, leading to modest sustained weight loss. While this sounds promising, the weight loss is less than expected due to compensatory increases in energy intake.

A Timeline of Weight Loss Treatments

The history of weight loss treatments is a rollercoaster ride through time:

• Soranus of Ephesus’ elixirs and purgatives (2nd century AD)
• Thyroid hormone treatment for obesity (1920s-1930s), with side effects including hyperthyroidism
• 2,4-Dinitrophenol (DNP) treatment (1933), which caused fatal hyperthermia and cataracts
• Ampethamines as weight loss aids (late 1930s-1967/1968)
• Senate investigation led to restrictions on diet pills (1967/1968), with rainbow diet pills banned in the late 1960s but reappearing in South America and Europe in the 1980s
• Phentermine and fenfluramine FDA approval (1959, 1973 respectively)
• Fen-phen combination popular in the 1990s but withdrawn due to valvular heart disease risks
• GLP-1 receptor agonists like semaglutide and tirzepatide became popular for weight loss, causing shortages and new approvals for chronic weight management

The Future of Anti-Obesity Medications

US FDA approves anti-obesity medications as adjunct therapy to diet and exercise for adults with high BMI or comorbidities. Semaglutide is approved for chronic weight management in adults with a BMI ≥ 30 or ≥ 27 with one weight-related comorbidity.

How will these new drugs change the landscape of obesity treatment? Will they finally provide the long-term solutions we’ve been searching for?

The journey of anti-obesity medications is a testament to human ingenuity and the relentless pursuit of better health. As we continue to explore new treatments, one thing remains clear: the battle against obesity will never be won by a single approach but through a combination of medical advancements, lifestyle changes, and societal support.