The Evolution of Weight Loss Drugs: From Past to Present
You know you’re ready to lose the weight and keep it off. But you have some concerns about weight loss medications. You’ve heard that weight loss medications are unsafe and ineffective. Are those rumors true? And, is there a better tool for lasting weight loss than weight loss drugs?
To answer these questions, it will be helpful to explore the history of weight loss medications over the past century and up to the present.
1st-Generation Weight Loss Medications
The very first weight loss medications were developed in the 1930s. These were stimulants, and included dinitrophenol and methamphetamine. The goal of these medications was to reduce patients’ appetite and speed up the metabolism. However, these first medications proved to be unsafe and highly addictive. Some are sill used in generic forms, but they are only approved for short-term use due to the risk of addiction.
After amphetamines came a range of weight loss medications in the mid and late 20th century, which varied in effectiveness but which would generally be considered both unsafe and ineffective in today’s terms. Human chorionic gonadotropin was released in 1960, with the goal of reducing food intake; but it was pulled from the market when it was shown to be ineffective. Aminorex was an appetite suppressant released in 1971, but it was discontinued because it caused pulmonary hypertension. Fenfluramine was another appetite suppressant, which was withdrawn from the market in 1997 for similar reasons.
2nd-Generation Weight Loss Medications
In the early 2000s, as doctors and scientists learned more about the causes of obesity, they developed a second generation of weight loss medications. These were both safer and more effective than earlier medications. These included Bupropion-naltrexone (Contrave®), which decreases hunger and reduces cravings; and Phentermine-topiramate (Qsymia®), which also decreases hunger and makes patients feel more full for longer.
These drugs led to more lasting weight loss than previous generations of drugs, but weight loss was still relatively low. Most patients could expect to lose 5-10% of their body weight while taking these medications in conjunction with dietary changes and exercise. However, the effect diminished with time, and weight generally returned once patients stopped taking the medications.
These medications also came with side effects, including headaches, insomnia, fatigue, depression, anxiety, constipation, nausea, increased blood pressure, and heart problems. Topiramate (an active ingredient in Qsymia®) could also increase the risk of birth defects. Even so, these side effects were generally milder and less common than the side effects of 1st-generation weight loss medications.
3rd-Generation GLP-1 Agonists (Semaglutide and Tirzepatide)
GLP-1 agonists represent the latest generation weight loss medications. They include semaglutide (the active ingredient in Ozempic and Wegovy) and tirzepatide (the active ingredient in Mounjaro and Zepbound). These medications were originally approved for treatment of type 2 diabetes, but due to their success at reducing hunger and creating feelings of fullness they are increasingly used to treat overweight and (to a lesser extent) obesity.
GLP-1 agonists can offer substantial weight loss. If you’re wondering which weight loss drug on the market is the most effective, the answer is tirzepatide, closely followed by semaglutide. Patients who take Mounjaro or Zepbound lose an average of 21% of their body weight, in conjunction with diet and exercise. Patients who take Ozempic or Wegovy lose an average of 16% of their body weight, again in conjunction with diet and exercise. However, it is very important to note that these losses progress slowly, and they are only sustained as long as the patient continues to take the medication. These are also averages, and some patients can be expected to lose more or less weight than these numbers would suggest.
What are the side effects of taking weight loss drugs?
GLP-1 agonists do have fewer serious side effects than many previous weight loss drugs, but fewer does not mean none. A JAMA Network study found that 48.6% of Ozempic patients experienced side effects. The most common side effects included nausea and vomiting (36.6% of patients), diarrhea (8.6%) and fatigue (6.3%). Side effects for Tirzepatide are similar but sometimes more prevalent and more severe. In the SURMOUNT-4 trial, fully 81% of Tirzepatide patients reported experiencing side effects. The most common side effects were nausea (35.5% of patients), diarrhea (21.1%), constipation (20.7%), and vomiting (16.3%). Side effects can also be more serious: a recent study found that semaglutide increased patients’ risk of gastroparesis or paralysis of the stomach so that it does not empty properly. Both medications can cause endocrine tumors such as thyroid and pancreatic tumors and possibly cancer, as well as pancreatitis.
These medications can work well to help patients who are suffering from an overweight status to lose weight, but it’s important to note that they are expensive and the side effects are more common than bariatric surgery and can be severe. Taken as a stand-alone, they are also unlikely to help patients who are suffering from obesity to lose as much weight as they are looking to lose.
All of this might leave you wondering: are weight loss pills safe? The short answer is that modern second-generation weight loss medications are far safer than earlier medications such as amphetamines or fenfluramine. However, they still come with many side effects, as evidenced by the 48.6% of semaglutide patients, and 81% of tirzepatide patients, who experience side effects ranking from nausea and vomiting to endocrine tumors.
(For a deeper dive into the efficacy, side effects, and safety of GLP-1 agonists, see our page on common misconceptions about weight loss medications)
Bariatric Surgery: A Better Alternative
If you are suffering from obesity, bariatric surgery can be a powerful tool to help you to lose weight and keep it off.
Bariatric surgery is very safe. At a certified ASMBS Center of Excellence like the BMCC, our complication rate is well under 5% and most are preventable by simply following our thorough safety protocols. Our double-board-certified bariatric surgeon personally commits to remaining in the operating room until every surgery is performed as well as humanly possible.
Weight loss surgery is also very powerful. In conjunction with dietary changes and exercise, most of our patients lose 65-100% of their excess body weight and keep it off. Many of our duodenal switch patients lose 90-100% of their excess body weight in the first 9 months, and never regain it. Imagine how life post-bariatric surgery would feel.
Most of our patients say that the decision to undergo bariatric surgery was the best decision they ever made. Post-bariatric surgery, many patients report less joint pain, more energy, more activity, and often a resolution of medical ailments such as type 2 diabetes.
“I feel like I have won the lottery and have been given a second chance in life! March 25, 2014 was the first day of the rest of my new life and I can’t even start to express in words how grateful I am.”–Rochelle Goforth, gastric bypass patient.
If you’re suffering, don’t wait. Contact our Denver office today.
