Obesity is a major problem in the United States. If we look back over the past 30 years, the obesity prevalence has increased every decade since 1990. Currently, the highest prevalence is in the Midwest (29.5%) and the South (29.4%).
Obesity is defined by and classified according to BMI, which ranges from underweight to morbidly obese. Overweight is defined as a BMI between 25.0 and 29.9, whereas obesity is defined as a BMI greater than 30. In the United States, one in every three adults is obese, compared with two in every three adults are overweight.
When talking to patients about obesity and desired weight loss, it is important to determine a predefined amount of weight that can be lost over a specific period of time. Typically, a weight loss goal of 5% to 10% is reasonable for patients. This particular percentage of weight loss has been shown to improve blood glucose and cholesterol levels, as well as blood pressure (BP) measurements. Goals should be individualized but follow the SMART method — specific, measurable, attainable, realistic and timely. Nonpharmacological interventions include calorie reduction, physical activity and behavior modifications.
Normally, drug therapy is initiated after 6 months of nonpharmacological interventions. Pharmacological therapy is indicated for patients with a BMI over 30 (i.e., obese) or a BMI over 27 (i.e., overweight) with a comorbid condition, such as hypertension, diabetes or hyperlipidemia.
As of Nov. 30, 2014, there were several agents on the market for the treatment of long-term obesity management (i.e., 1 to 2 years). These medications include orlistat (Alli, Xenical), lorcaserin (Belviq), phentermine/topiramate (Qsymia) and bupropion/naltrexone (Contrave). On Dec. 23, 2014, the Food and Drug Administration (FDA) approved another agent — liraglutide (Saxenda) — as the first (and only) once-daily injectable product for chronic weight management.
Saxenda’s indication is weight loss in combination with a reduced caloric diet and increased physical activity and is available in a 3.0-mg dose. This type of drug is classified as a glucagon-like peptide-1 (GLP-1) receptor agonist. This particular agent does have some warnings, such as thyroid cell carcinomas. This type of cancer has only been found in rats, and the link to humans is unknown. Another warning is pancreatitis, which is a warning for all GLP-1 agonists (i.e., exenatide, albiglutide, and dulaglutide) indicated for the management of type 2 diabetes. If pancreatitis is suspected, then the medication should be stopped immediately and should not be reinitiated. Caution should be used among patients with renal and hepatic impairment who may be a candidate for liraglutide.
GLP is a gastrointestinal hormone that is able to regulate insulin released in response to a meal. Upon glucose load (i.e., meal), GLP is released to inhibit the release of glucagon and increase the release of insulin. This mechanism of action is essential when controlling glucose levels among patients with diabetes. For diabetes and obesity management, patients may lose weight with GLP-1 agonists due to other unique actions. GLP-1 agonists can slow gastric emptying and increase satiety.
In a double-blind, placebo-controlled, active comparator study, liraglutide was investigated in overweight and obese adult patients without diabetes. The comparator arms were placebo and orlistat. The dose of liraglutide was 1.2 mg, 1.8 mg, 2.4 mg or 3 mg subcutaneously once daily. The primary endpoint was change in body weight and proportion of patients who lost 5% or 10% of body weight from baseline. There were additional secondary endpoints, such as change in specific metabolic parameters and patient quality of life.
In this particular study, there was a dose-dependent reduction in body weight among patients receiving liraglutide. Patients on liraglutide lost significantly more weight than those patients receiving orlistat and placebo.
While these results were promising, the safety profile of liraglutide should also be considered. Gastrointestinal side effects, especially nausea, occurred in a dose-dependent manner among patients receiving liraglutide. The downside of this trial was its short duration (i.e., 20 weeks). A longer trial was conducted using the same type of study population and interventions. After 1 and 1 years, more patients on liraglutide lost 5% from baseline, compared with placebo. Nausea continued to be the most common adverse event.
In another long-term, placebo-controlled study, liraglutide-treated patients had a 6.9% reduction in body weight from baseline to 56 weeks. Among all the trials, liraglutide met the FDA criteria for weight loss, which is a placebo-subtracted reduction in body weight by 5% or more.
While there is good evidence behind liraglutide for weight loss, there are several things to take into consideration. This drug will have to find a niche in obesity management considering the other agents that are available as oral products. Liraglutide also has other drawbacks, such as nausea being the most common side effect and cost of the medication.
Obesity is an overwhelming health risk and has increased the global cost of health care over several years. Until 2012, pharmacological options were quite limited for weight loss and maintenance. However, practitioners should select a particular agent based on certain factors of the patient.
Jennifer N. Clements, PharmD, BCPS, CDE, BCACP, joined the faculty at Presbyterian College School of Pharmacy in August 2012. She is board-certified in pharmacotherapy and ambulatory care, and is also a certified diabetes educator.