Weight Loss Drugs
As a Registered Dietitian, the topic of weight loss drugs is HUGE. Many of my clients ask about them and you may also be wondering if they are safe, if they work, and if you should try them. This post is a summary of the popular weight loss drugs, what they do and how they do it, who they benefit, and what some of the benefits and risks are.
More than 39% of the global adult population are classified as overweight (BMI 25-29.9) or obese (BMI 30+). Related complications include diabetes, cardiovascular disease, cancer, mental health conditions, and lower quality of life [1]. The main response to obesity for many years has been to exercise more and eat less. However, the age-old advice has not been able to control the growing number of individuals experiencing obesity and its health-related conditions. This review covers the weight loss medications on the market today, their efficacy, along with side effects. Most people with a BMI < 27 and a comorbidity or a BMI < 30 can qualify to receive a prescription for these drugs. The research shows promise for weight loss in combining certain weight loss medications with behavior modification under the direction of a physician and a registered dietitian.
One of the medications that has been around the longest is Phentermine, which initially came out in 1959 [2]. It was combined with another medication, Topiramate, an anticonvulsant and approved by the FDA and released in 2012. Phentermine-topiramate is a once per day pill taken around breakfast that reduces appetite and causes feelings of fullness. It is meant to be just a piece of a weight loss plan built around diet and exercise and can be prescribed only up to 12 weeks. Notable symptoms include: increased heart rate, insomnia, nervousness, constipation, dry mouth, and mood swings.
Another popular weight loss drug on the market is Orlistat, which is a lipase inhibitor approved in 1999. It is the only drug that acts on the metabolism by reducing fat absorption and thereby lowering caloric intake. The drug has been shown to decrease fat absorption from food by 33% [3]. The pill is taken 3 times a day before meals. In clinical trials, Orlistat showed a 3% weight loss over placebo [2]. It is also notably the only weight loss drug approved for adolescents to take. Side effects include: oily stools, spotting, flatus, and fecal urgency. Due to the limited fat absorption with this drug, a fat-soluble vitamin (ADEK) supplement is recommended. Because of its mechanism of action, Orlistat is recommended for people who eat a high fat diet.
Another drug on the market is Naltrexone/Bupropion, popularly branded as Contrave. Naltrexone was initially used to treat alcohol, nicotine, and opioid addiction. Bupropion was an antidepressant used to help people with Seasonal Affective Disorder and also for smoking cessation. Combined, Naltrexone/Bupropion acts as an opioid receptor antagonist, dopamine agonist, and norepinephrine reuptake inhibitor [3]. This works to increase satiety and suppress appetite. It is often used for long-term weight management. In 4 clinical trials lasting 56 weeks with subjects who had a BMI >27 with a comorbidity, subjects showed weight loss between 6-9% of total body weight. The downside of this drug are its known side effects, which include: nausea, headache, constipation, dizziness, vomiting, and dry mouth.
A popular GLP-1 agonist is the oral drug Liraglutide (Victoza), which was approved by the FDA in 2010 for the treatment of Type 2 Diabetes. Like Naltrexone/Bupropion, it is meant for long-term weight management. Liraglutide is used to slow gastric emptying, increase satiety and fullness, and help lower blood glucose by enhancing insulin secretion and inhibiting the release of glucagon. It also prevents the liver from taking in and storing glucose [3]. Clinical studies show an average weight loss between 6-8% of total body fat. However, liraglutides have the highest rate of discontinuation amongst clinical trials (13%) due to the negative side effects. These include: nausea, vomiting, diarrhea, constipation, and dyspepsia. It is interesting to note that animal studies involving Liraglutide have shown pancreatic, intestinal, and breast tumors, but they have not been replicated in human studies. That said, Lorcaserin (Belviq, Belviq HR), a weight loss drug that came out in 2012 was recently pulled in 2020 by the FDA for increased prevalence of cancer [4]. When choosing weight loss drugs, it is always important to weight the benefits over the risks.
One of the most popular, newer medications are semaglutides, like Wegovy. This medication obtained FDA approval in 2021. It is a once weekly injection that helps the pancreas to release insulin as needed, decreases appetite, and blocks a hormone that causes the liver to release sugar. Affecting GLP-1, it slows down gastric emptying. In a major clinical trial lasting 68 weeks and with 1,961 people, the semaglutide group lost 14.9% body weight compared with 2.4% loss in the placebo group [5]. This translates to about 34 lbs with semaglutides and only 6 lbs with placebo. Other benefits reported include: greater improvement in cardiovascular risk factors and a participant-reported improvement in physical functioning. Nausea and diarrhea are the most common side effects reported on this medication, which were notably improved with time.
The newest medication to hit the market in May 2022 is Tirzepatide, under the brand name Mounjaro. It was originally a drug to help control Type 2 DM, but has become popular for obesity treatment. It acts as both a glucagon-like peptide 1 (GLP-1) and a glucose dependent insulinotropic peptide (GIP) receptor agonist. These two hormones are incretins, or products that stimulate beta cells to release insulin. The result is significantly lowered glycemic levels and improved insulin sensitivity [6]. This leads to decreased food intake, decreased appetite, and increased weight loss. In 5 clinical trials, Mounjaro showed an average weight loss of 15 lbs more than the placebo group [7]. It also lowered HbA1C levels 1.6 times more than placebo. Mounjaro is a once a week shot. Side effects include nausea, vomiting, diarrhea, decreased appetite, constipation, upper ab discomfort, and ab pain. It should also be noted that this medication causes thyroid C-cell tumors in rats.
In summary, there are several good options for weight loss medications that do help patients lose weight more than they could do on their own with behavior and lifestyle changes. However, the side effects should be considered and the drug abandoned when side effects lower quality of life more than obesity did. Weight maintenance should also be considered. In one study, after significant weight loss, 1/3 of the population gained it back in a year, ½ gained it back in 2 years, and almost all gained their weight back in 5 years [3]. Permanent behavior change and habit formation is key to keeping weight off. Weight loss drugs should be given under the direction of a doctor and alongside regular meetings with a dietitian to give clients their best chance at permanent weight loss.
References
1. Morgan-Bathke M, Baxter SD, Halliday TM, et al. Weight Management Interventions Provided by a Dietitian for Adults with Overweight or Obesity: An Evidence Analysis Center Systematic Review and Meta-Analysis. Journal of the Academy of Nutrition and Dietetics doi: 10.1016/j.jand.2022.03.014.
2. Gadde KM, Martin CK, Berthoud HR, Heymsfield SB. Obesity: Pathophysiology and Management. J Am Coll Cardiol 2018;71(1):69-84 doi: 10.1016/j.jacc.2017.11.011.
3. Tak YJ, Lee SY. Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand? Curr Obes Rep 2021;10(1):14-30 doi: 10.1007/s13679-020-00422-w.
4. FDA. Safety clinical trial shows possible increased risk of cancer with weight-loss medicine Belviq, Belviq XR (lorcaserin), 2020.
5. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2021;384(11):989-1002 doi: 10.1056/NEJMoa2032183.
6. Chavda VP, Ajabiya J, Teli D, Bojarska J, Apostolopoulos V. Tirzepatide, a New Era of Dual-Targeted Treatment for Diabetes and Obesity: A Mini-Review. Molecules 2022;27(13) doi: 10.3390/molecules27134315.
7. FDA. FDA Approves Novel, Dual-Targeted Treatment for Type 2 Diabetes: FDA, 2022.
