A Deep Dive into Obesity Medications: Efficacy, Side Effects, and Contraindications

Obesity is a chronic, multifaceted disease that poses significant health risks, including diabetes, cardiovascular disease, and certain cancers. Pharmacotherapy for obesity has evolved significantly, providing patients with more options to aid in weight management. This blog post delves into the major obesity medications available, focusing on their approval timelines, efficacy, side effects, contraindications, and availability as generic or brand name drugs.

Orlistat (Xenical, Alli)

Approval and Mechanism: Orlistat was approved by the FDA in 1999 for prescription use under the brand name Xenical and in 2007 for over-the-counter use as Alli. It works by inhibiting pancreatic lipase, thereby reducing fat absorption in the intestines.

Efficacy: Clinical trials have shown that orlistat can result in an average weight loss of 5-10% of initial body weight over one year when combined with a calorie-restricted diet (Hauptman et al., 2000).

Side Effects: The most common side effects are gastrointestinal, including oily stools, flatulence, and frequent bowel movements. These side effects are typically dose-dependent and can be managed with dietary adjustments.

Contraindications: Orlistat is contraindicated in patients with chronic malabsorption syndrome or cholestasis. Caution is also advised for patients with a history of kidney stones.

Availability: Orlistat is available as a generic drug and under the brand names Xenical (prescription) and Alli (over-the-counter).

Phentermine-Topiramate (Qsymia)

Approval and Mechanism: Approved by the FDA in 2012, Qsymia combines phentermine, an appetite suppressant, with topiramate, an anticonvulsant that promotes satiety.

Efficacy: Clinical studies indicate that Qsymia can lead to an average weight loss of 6.6-8.6% of initial body weight over one year (Garvey et al., 2012).

Side Effects: Common side effects include dry mouth, constipation, paraesthesia, dizziness, and insomnia. There are also risks of cognitive impairment and mood changes.

Contraindications: Qsymia is contraindicated in pregnancy due to the risk of fetal harm. It should also be avoided in patients with glaucoma, hyperthyroidism, and recent or unstable heart disease.

Availability: Qsymia is available only as a brand name drug.

Lorcaserin (Belviq)

Approval and Mechanism: Lorcaserin was approved by the FDA in 2012. It acts as a selective serotonin 2C receptor agonist, reducing appetite.

Efficacy: Clinical trials showed that lorcaserin can lead to an average weight loss of 3-5% of initial body weight over one year (Smith et al., 2010).

Side Effects: Common side effects include headache, dizziness, fatigue, nausea, dry mouth, and constipation. Serious side effects may include serotonin syndrome, particularly if taken with other serotonergic drugs.

Contraindications: Lorcaserin is contraindicated in pregnancy and in patients with severe renal impairment. It should be used cautiously in patients with a history of valvular heart disease.

Availability: Lorcaserin was available as a brand name drug (Belviq) but was withdrawn from the market in 2020 due to an increased risk of cancer observed in post-marketing studies.

Naltrexone-Bupropion (Contrave)

Approval and Mechanism: Approved by the FDA in 2014, Contrave combines naltrexone, an opioid antagonist, with bupropion, an antidepressant. This combination works to reduce appetite and cravings.

Efficacy: Studies have shown that Contrave can lead to an average weight loss of 4-5% of initial body weight over one year (Greenway et al., 2010).

Side Effects: Common side effects include nausea, headache, constipation, dizziness, and insomnia. There are also risks of increased blood pressure and heart rate.

Contraindications: Contrave is contraindicated in patients with uncontrolled hypertension, seizure disorders, anorexia or bulimia nervosa, and those undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs. It is also contraindicated in pregnancy.

Availability: Contrave is available only as a brand name drug.

Liraglutide (Saxenda)

Approval and Mechanism: Approved by the FDA in 2014 for weight management, Saxenda is a GLP-1 receptor agonist that enhances insulin secretion and reduces appetite.

Efficacy: Clinical trials have shown that liraglutide can result in an average weight loss of 8-10% of initial body weight over one year (Pi-Sunyer et al., 2015).

Side Effects: Common side effects include nausea, vomiting, diarrhea, constipation, and hypoglycemia. There are also risks of pancreatitis and gallbladder disease.

Contraindications: Liraglutide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. It should also be avoided in patients with severe renal impairment.

Availability: Saxenda is available only as a brand name drug.

Semaglutide (Wegovy)

Approval and Mechanism: Approved by the FDA in 2021 for weight management, semaglutide is another GLP-1 receptor agonist with a similar mechanism to liraglutide.

Efficacy: Semaglutide has shown significant efficacy, with clinical trials demonstrating an average weight loss of 12-15% of initial body weight over one year (Wilding et al., 2021).

Side Effects: Common side effects include nausea, vomiting, diarrhea, constipation, and abdominal pain. Serious side effects may include pancreatitis and increased risk of thyroid tumors.

Contraindications: Semaglutide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. It should also be used cautiously in patients with a history of pancreatitis.

Availability: Wegovy is available only as a brand name drug.

Conclusion

Pharmacotherapy for obesity offers various options, each with distinct mechanisms, efficacy, side effects, and contraindications. As with any medication, the choice of obesity treatment should be individualized, considering the patient's medical history, comorbidities, and potential drug interactions. Physicians must remain vigilant about monitoring and managing any adverse effects to ensure the safety and effectiveness of these treatments.