Metabolic syndrome can be defined as a state of disturbed metabolic homeostasis characterized by visceral obesity, atherogenic dyslipidemia, arterial hypertension, and insulin resistance. The growing prevalence of metabolic syndrome will certainly contribute to the burden of cardiovascular disease. Obesity and dyslipidemia are main features of metabolic syndrome, and both can present with adipose tissue dysfunction, involved in the pathogenic mechanisms underlying this syndrome. We revised the effects, and underlying mechanisms, of the current approved drugs for dyslipidemia and obesity (fibrates, statins, niacin, resins, ezetimibe, and orlistat; sibutramine; and diethylpropion, phentermine/topiramate, bupropion and naltrexone, and liraglutide) on adipose tissue. Specifically, we explored how these drugs can modulate the complex pathways involved in metabolism, inflammation, atherogenesis, insulin sensitivity, and adipogenesis. The clinical outcomes of adipose tissue modulation by these drugs, as well as differences of major importance for clinical practice between drugs of the same class, were identified. Whether solutions to these issues will be found in further adjustments and combinations between drugs already in use or necessarily in new advances in pharmacology is not known. To better understand the effect of drugs used in dyslipidemia and obesity on adipose tissue not only is challenging for physicians but could also be the next step to tackle cardiovascular disease.

Phentermine and extended-release (ER) topiramate have been used separately in a variety of ways. Phentermine was first introduced in 1959 as part of an anti-obesity combination drug. Topiramate was discovered in 1979 but was not released for commercial use until 1996. Phentermine on its own has been used for short-term treatment of obesity in combination with exercise and caloric restriction. Topiramate on its own has been used to treat partial-onset or primary generalized tonic-clonic seizures, Lennox-Gastaut syndrome, and as prophylactic treatment of migraine headaches. The United States Food and Drug Administration approved the combination of these 2 drugs in 2012 for the treatment of obesity. The drugs are used in combination with reduced calorie diet and exercise in individuals with an initial body mass index (BMI) over 30 kg/m2 or in those with a BMI of over 27 in combination with at least one obesity-related comorbidity.

The prevalence of obesity and associated comorbidities is rising. Despite their weight-loss efficacy, new generation anti-obesity medications are only prescribed to a minority of adults with obesity, possibly, which in part may be due to safety concerns. This review presents detailed safety profiles for orlistat, phentermine/topiramate, lorcaserin, naltrexone/bupropion and liraglutide 3.0 mg, and discusses the associated risk-benefit profiles. Two anti-obesity medications presented safety issues that warranted further discussion; phentermine/topiramate (fetal toxicity) and liraglutide 3.0 mg (risk of gallstone disease and mild, acute pancreatitis), whereas the adverse events associated with orlistat, lorcaserin, and naltrexone/bupropion were mostly transient tolerability issues. The difficulties surrounding the objective determination of risk-benefit for anti-obesity medications is discussed. The need for more long-term data, thorough patient assessment, individualization of pharmacological interventions and adherence to stopping rules to maximize risk-benefit are highlighted. Overall, the majority of new generation anti-obesity medications present encouraging tolerability profiles; however, in some cases a lack of long-term clinical trials confounds the accurate determination of risk-benefit.

Type 2 diabetes (T2DM) is associated with significant morbidity and mortality. Obesity is one of the main risk factors for T2DM and its management requires a multidisciplinary approach, which may include pharmacotherapy. Areas covered: In this paper, data on efficacy, tolerability and safety of FDA-approved pharmacotherapies for obesity (orlistat, phentermine/topiramate extended-release, lorcaserin, bupropion sustained release/naltrexone sustained release and liraglutide) are reviewed, focusing on individuals with type 2 diabetes. Expert opinion: Obesity is the major pathophysiologic driver of T2DM; conversely 5-10% weight loss leads to significant improvement in glycemic control, lipids and blood pressure. Weight loss maintenance is difficult with lifestyle interventions alone and may require adjunctive therapies. There is good evidence for the efficacy and tolerability of approved anti-obesity pharmacotherapies in individuals with T2DM, with current cardiovascular safety data being most favorable for liraglutide, orlistat and lorcaserin. Given the link between obesity and T2DM, a weight-centric therapeutic approach including use of weight reducing anti-diabetic therapies, and anti-obesity pharmacotherapies is both intuitive and rational to improve glycemic and other metabolic outcomes in patients with T2DM.

Obesity continues to be among the top health concerns across the globe. Despite our failure to contain the high prevalence of obesity, we now have a better understanding of its pathophysiology, and how excess adiposity leads to type 2 diabetes, hypertension, and cardiovascular disease. Lifestyle modification is recommended as the cornerstone of obesity management, but many patients do not achieve long-lasting benefits due to difficulty with adherence as well as physiological and neurohormonal adaptation of the body in response to weight loss. Fortunately, 5 drug therapies-orlistat, lorcaserin, liraglutide, phentermine/topiramate, and naltrexone/bupropion-are available for long-term weight management. Additionally, several medical devices are available for short-term and long-term use. Bariatric surgery yields substantial and sustained weight loss with resolution of type 2 diabetes, although due to the high cost and a small risk of serious complications, it is generally recommended for patients with severe obesity. Benefit-to-risk balance should guide treatment decisions.

Weight loss drugs or anti-obesity drugs have a long history but are still far from being successful. Only in two last decades have the drugs been launched, which, when appropriately indicated, may be significantly beneficial to patients in need of weight loss as they are comparably effective to intensive programs to promote changes in eating habits and lifestyles. The combination naltrexone/bupropion is promising for food intake control including the reward mechanism, but the experience with its use has only been short-term. The lipase inhibitor orlistat remains the safest therapeutic option. The already restricted use of phentermine, newly classified as a controlled opiate substance, has become practically blocked. The range of weight loss drugs can be extended with some antidiabetics, particularly liraglutide and gliflozins. A number of other substances is still in the research stage.