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Diabetes Management The Role of Anti-obesity Drugs in Patients with Type 2 Diabetes Priscilla Hollander, MD, PhD Medical Director, Ruth Collins Diabetes Center, Baylor University Medical Center, Dallas, Texas, US Abstract The prevalence of diabetes continues to rise, following the rising rates of obesity. Obesity is not only associated with an increased risk for developing type 2 diabetes but also an elevated probability of developing long-term complications associated with the disease. Weight gain is also an important concern as a potential side effect of therapies that improve glycemic control in diabetes, including insulin therapy. As a result, patients with type 2 diabetes are at risk for a vicious circle of increasing weight and increasing insulin resistance, thus requiring further intensification of glycemic treatment. It is therefore important to address the problem of obesity in patients with type 2 diabetes. In 2012, the US Food and Drug Administration (FDA) approved two new anti-obesity medications: lorcaserin and phentermine/topiramate extended-release. Both agents have demonstrated clinically meaningful weight reduction as well as significant improvements in glycemic control in obese patients with diabetes. Liraglutide has also shown weight loss and improvements in glycemic control in patients with diabetes. Anti-obesity drugs, in conjunction with lifestyle changes, may play a valuable role in the management of diabetes. Keywords Diabetes, liraglutide, lorcaserin, obesity, phentermine/topiramate extended-release Disclosure: Priscilla Hollander, MD, PhD, has been a member of advisory boards for Genentech, Johnson & Johnson, Novo Nordisk, and Merck. Acknowledgments: Editorial assistance was provided by Katrina Mountfort, PhD, at Touch Medical Media. Received: November 18, 2013 Accepted: December 2, 2013 Citation: US Endocrinology 2013;9(2):101–7 Correspondence: Priscilla Hollander, MD, PhD, Baylor Endocrine Center, 3600 Gaston Ave, Dallas, TX 75246, US. E: Support: The publication of this article was supported by Eisai. The views and opinions expressed are those of the author and not necessarily those of Eisai. The prevalence of overweight and obesity among patients with type 2 diabetes is extremely high. Data from two national surveys indicate that 28 % of individuals with diabetes were overweight and 59 % were obese. 1 Furthermore, a rise in body mass index (BMI) is directly correlated to an increased risk for diabetes. 2–4 The prevalence of type 2 diabetes is three to seven times higher in obese adults than in those of normal weight, and adults with a BMI >35 kg/m 2 are 20 times more likely to develop diabetes than those with a BMI between 18.5 and 24.9 kg/m 2 . 5,6 Prediabetes and the metabolic syndrome are also associated with obesity. 7 Obesity is not only associated with an increased risk for developing type 2 diabetes but also an elevated probability of developing microvascular, 8 neuropathic, 8,9 and cardiovascular 10,11 complications associated with the disease. The incidence of type 2 diabetes has risen in parallel with the global increase in obesity, which can be illustrated by examining US data (see Figure 1). The prevalence of obesity is leveling out in the US population, but the prevalence of diabetes is rising. The presence of diabetes parallels the prevalence of obesity, but follows obesity by about 10 years. 12 This has important health and economic implications. The total number of people with diabetes worldwide is projected to rise from 366 million in 2012 to 552 million in 2030. 13 Projections also suggest that there will be 65 million more obese adults in the US by 2030, resulting in an additional 6–8.5 million cases of diabetes. 14 Obesity is also associated with elevated risk for long-term complications, such as cardiovascular disease (CVD), in people © TO U CH MEDICAL MED IA 2013 with type 2 diabetes. 15 Strategies to combat the increasing incidence of diabetes should therefore also focus on the obesity epidemic. The transition from obesity to type 2 diabetes is characterized by a progressive deficiency in insulin secretion accompanied by a rise in insulin resistance. 16 Numerous mechanisms underlie these changes, including adipose tissue dysfunction, which results in impaired insulin sensitivity in adipocytes 17 and secretion of numerous factors that are involved in the development of insulin resistance, such as non-esterified or free fatty acids (FFAs), glycerol, hormones, and pro-inflammatory cytokines. 18 Chronic elevations in FFAs have also been implicated as a causative factor in pancreatic b-cell dysfunction. 19 This article aims to consider the role of pharmacologic therapies to control obesity in individuals with type 2 diabetes. Effect of Type 2 Diabetes Therapy on Bodyweight The current treatment goal in type 2 diabetes is to achieve the best possible glycemic control, since intensive glycemic control has been associated with a substantially decreased risk for microvascular complications. 20 Clinical evidence has also suggested a beneficial role for glycemic control on CVD, depending on patient characteristics, including age, diabetes duration, previous glucose control, and risk for hypoglycemia. 21 CVD is the major cause of death in patients with type 2 diabetes; more than 60 % of patients die of myocardial infarction (MI) or stroke. 22 101