Diabetes Metab J.  2020 Dec;44(6):802-818. 10.4093/dmj.2020.0258.

Comprehensive Review of Current and Upcoming Anti-Obesity Drugs

• Son JW
• Kim S

• KMID: 2513044
• DOI: http://doi.org/10.4093/dmj.2020.0258

Abstract

Obesity is among the leading causes of morbidity and mortality worldwide and its prevalence continues to increase globally. Because obesity is a chronic, complex, and heterogeneous disease influenced by genetic, developmental, biological, and environmental factors, it is necessary to approach obesity with an integrated and comprehensive treatment strategy. As it is difficult to achieve and sustain successful long-term weight loss in most patients with obesity through lifestyle modifications (e.g., diet, exercise, and behavioral therapy), pharmacological approaches to the treatment of obesity should be considered as an adjunct therapy. Currently, four drugs (orlistat, naltrexone extended-release [ER]/bupropion ER, phentermine/topiramate controlled-release, and liraglutide) can be used long-term (>12 weeks) to promote weight loss by suppressing appetite or decreasing fat absorption. Pharmacotherapy for obesity should be conducted according to a proper assessment of the clinical evidence and customized to individual patients considering the characteristics of each drug and comorbidities associated with obesity. In this review, we discuss the mechanisms of action, efficacy, and safety of these available long-term anti-obesity drugs and introduce other potential agents under investigation. Furthermore, we discuss the need for research on personalized obesity medicine.

Keyword

Bupropion; Drug therapy; Liraglutide; Naltrexone; Obesity; Orlistat; Phentermine; Topiramate; Weight loss

Figure

• 

  Fig. 1 Mechanism of action and dosing schedule of anti-obesity drugs. Some images were downloaded from the Smart Servier website. MCH, melanin-concentrating hormone; TRH, thyrotropin-releasing hormone; CRH, corticotropin-releasing hormone; MC3/4R, melanocortin receptor type 3/4 receptor; Y1R, Y1 receptor; GABA, gamma-aminobutyric acid; GLP1R, glucagon-like peptide 1 receptor; D1, dopamine 1 receptor; D2, dopamine 2 receptor; POMC/CART, pro-opiomelanocortin/cocaine amphetamine-related transcript (anorexigenic); μ-OR, μ-opioid receptor; NPY/AGRP, neuropeptide Y/agouti-related peptide (orexigenic); DAT, dopamine active transporter.

• 

  Fig. 2 The effect of currently approved long-term therapies for obesity on weight loss. EQUATE, evaluation of phentermine and topiramate versus phentermine/topiramate extended-release in obese adults; EQUIP, controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial; CONQUER, Controlled-Release Phentermine plus Topiramate Combination in Overweight and Obese Adults; SEQUEL, 2-year Sustained Weight Loss and Metabolic Benefits with Controlled-release Phentermine/Topiramate in Obese and Overweight Adults; SCALE, Satiety and Clinical Adiposity—Liraglutide Evidence in Nondiabetic and Diabetic Individuals; COR, Contrave Obesity Research; BMOD, behavior modification; LIGHT, long-term intervention with group-wise dietary consulting supported by meal replacements maintaing weight loss in patients with concomitant obesity and knee osteoarthritis; XENDOS, Xenical in the Prevention of Diabetes in Obese Subjects.

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  Fig. 3 Choice of anti-obesity drugs based on obesity-associated comorbidities. BMI, body mass index; CVD, cardiovascular disease; NASH, non-alcoholic steatohepatitis; PCOS, polycystic ovary syndrome. aIncrease heart rate.

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