Treatment strategies for obesity include lifestyle modifications, surgery, and pharmacotherapy- most recently, new generation anti-obesity medications having shown better tolerability with minimal side effects in addition to sustained weight loss among the obese.

 

 

 

Obesity is a fast-growing public health problem and is found to be associated with substantial increases in morbidity, premature mortality, impaired quality of life and large healthcare costs.Lifestyle interventions in the form of diet and exercise are considered the first-line treatment for obesity but generally they do not produce marked or sustainable weight loss..Bariatric surgery is much more effective in terms of weight loss, comorbidity reduction, and enhanced survival, but factors like patient and physician perceptions, lack of resources, and cost burden all act as barriers to utilisation

That is where Anti-obesity medications (AOMs) come into the picture.  They can reduce body weight by decreasing the consumption or absorption of food, and/or by increasing energy expenditure. AOMs are indicated for patients with a body mass index (BMI) >30 kg/m² or BMI of >27 kg/m² with comorbidity and can be an alternative strategy to surgery to achieve clinically meaningful weight loss. Pharmacotherapy can help individuals achieve on average, 5 to 15% weight loss, which ultimately leads to significant improvements in many comorbid conditions, including hypertension, diabetes, hyperlipidaemia, and others.

---

Approved AOMs are backed by solid data

Older AOMs were associated with serious side effects which led to the historic market withdrawal of some of these agents. Fenfluramine was withdrawn due to concerns over valvular heart disease and sibutramine was withdrawn due to increased risk for stroke and myocardial infarction.

Due to this major concern, all classes of new-generation AOMs are subject to detailed investigation of potential side effects particularly cardiovascular safety issues. The US FDA has approved five AOMs for long-term use and they all are backed by solid data on long-term efficacy and safety.

Orlistat

Mechanism of Action: Orlistat inhibits pancreatic lipase and prevents the hydrolysis of triglycerides in the gut, thus resulting in decreased triglyceride absorption in the gut and reduction in overall caloric intake.

Clinical Effects: Research shows that Orlistat in combination with behavioural counselling was found to double weight loss in comparison to placebo/counselling. Progression to diabetes was also found to be reduced.

Adverse Effects: Treatment-related adverse events include increased flatulence, oily spotting, greasy loose stools, faecal urgency, or frank incontinence. In the XENDOS trial, 91% of individuals experienced at least one gastrointestinal event with orlistat. No known serious adverse effects have been associated, however, there have been reports of worsening of hepatic function early in the treatment.

Precautions & Contraindications: Due to decreased triglyceride absorption in the gut, a significant decrease in the absorption of vitamins A, D, E, and K has been observed. Hence, supplementation of diet with concomitant multivitamins and beta-carotene is advised for individuals taking orlistat. A risk of colorectal cancer and kidney stones has been associated with Orlistat. It is contraindicated in pregnancy, cholestasis, and chronic malabsorption syndromes.

Phentermine/Topiramate ER

Mechanism of Action: Phentermine is a sympathomimetic which suppresses appetite whereas topiramate is an anticonvulsant. Even though the exact weight loss mechanism of topiramate is yet to be elucidated, there are reports that indicate that topiramate promotes satiety and some reports suggest it decrease gluconeogenesis.

Clinical Effects: Additive effect of both drugs leads to more weight loss than either drug alone.

Adverse Effects: Common adverse events include dry mouth, insomnia, dysgeusia, and paraesthesia. Phentermine has the potential to increase both heart rate and blood pressure.

Precautions & Contraindications: Phentermine/topiramate ER is contraindicated in pregnancy as topiramate is associated with the risk of oral clefts in new-borns.

Lorcaserin

Mechanism of Action: Lorcaserin is a member of the serotonergic drug class and selectively targets the 5-HT-2C receptor and is involved in appetite control. 5-HT-2B receptor activation can increase the risk of valvulopathy.

Clinical Effects: Lorcaserin is associated with modest efficacy but it has demonstrated slightly improved values with respect to cardiac risk factors like blood pressure, heart rate, glycaemic control, and lipids.

Adverse Effects: Due to activation of the serotonin-2C receptor, there is a possibility of serotonin syndrome. Other common side effects include headaches, nausea, dizziness, and fatigue.

Precautions & Contraindications: It is contradicted in pregnancy and caution should be exercised when used with other serotonergic or antidopaminergic agents.

Naltrexone/Bupropion

Mechanism of Action: The drug’s exact mechanism of action responsible for weight loss is not clear, however the combination works synergistically in the hypothalamus and the mesolimbic dopamine circuit and ultimately promotes satiety and decreased food intake.

Clinical Effects: In combination with diet and exercise, the combination is reported to enable weight loss of more than 12% and has also demonstrated improved glycaemic control.

Adverse Effects: Common side effects include nausea, headaches, and constipation.

Precautions & Contraindications: There is a risk of cardiovascular effects and seizures, which is attributed to the bupropion component. It is contraindicated in patients who concurrently take an opiate medication as there is a risk of fulminant opioid withdrawal.

Liraglutide 3.0 mg

Mechanism of Action: Liraglutide is a Glucagon-like peptide 1 (GLP-1) receptor agonists and thus cause a reduction in energy intake which aids weight loss.

Clinical Effects: In the SCALE programme, Liraglutide was shown to reduce body weight and improve glucose metabolism.

Adverse Effects: Common side effects include nausea and gastrointestinal symptoms.

Precautions: An increased risk of pancreatitis and gallstone development has been associated with Liraglutide.

---

Even though AOMs provide clinically meaningful weight loss and help improve the condition of patients with many obesity-related comorbidities, only a small percentage of patients are prescribed these drugs. This may be attributed to the historic concerns of serious adverse events associated with the older agents and the high cost of these drugs. The requirement of subcutaneous injection for some agents like liraglutide can also be a reason for concern.

New generation AOMs can prove to be a safe and tolerable option to individuals with obesity however effective post-marketing surveillance and additional trials to test their long-term safety are the need of the hour. Clinicians should assess the risk to benefit ratio for each individual before prescribing these agents. Strategies such as in-depth patient-assessments (beyond BMI) and following stopping rules can help to effectively decide on the right therapy for the right individual.