Drug Induced Weight Gain and its Impact on Health
June 18, 2010
Louis J. Aronne, MD, FACP
Adipose (fatty) tissue is an endocrine organ that is known to express molecules that act both locally and systemically. Abdominal obesity, in particular, leads to excess secretion of free fatty acids (FFAs) and many adipocytokines (bioactive product produced by adipose tissue) including leptin, and inflammatory molecules, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemoattractant factor 1 (MCP-1), C-reactive protein (CRP), and the prothrombotic plasminogen activator inhibitor type 1 (PAI-1). In addition, excess adipose tissue is also associated with declining secretion of adiponectin, an adipose tissue-derived hormone with antiatherogenic and antidiabetic properties (properties that could protect against heart disease and diabetes, respectively). The endocrine function of adipose tissue explains the relationship between weight gain and an increase in the risk of developing the complications of obesity. Thus, in comparison to treatments that result in weight loss, medications used to treat type 2 diabetes that cause weight gain can be expected to either worsen these risk factors, or not improve them to the same degree. The benefit of using treatments for type 2 diabetes that also cause weight loss is clear: there are multiple other illnesses besides diabetes, including heart disease, stroke, fatty liver, sleep apnea, and several cancers, that are associated with obesity and could be expected to improve with weight loss.
Agents that target the GLP-1 pathway have been shown to impact glycemic control and weight in patients with type 2 diabetes. There have also been studies showing that these agents have effects on cardiometabolic markers, as well as markers of oxidative stress. These effects may prove to be important considerations when selecting treatment options for patients with type 2 diabetes, as most are clinically overweight or obese.
A major focus of our current strategy in managing obese patients with type 2 diabetes is to treat with medications that cause weight loss, rather than those which would cause weight gain. This approach allows the patients to achieve the additional metabolic benefit associated with weight loss. The drugs I favor in managing patients with type 2 diabetes include biguanides, GLP-1 agonists, and amylin agonists, which may cause significant weight loss. In many patients, we use these compounds, along with our online behavioral program www.cmsnonline.com, to produce weight loss. Alpha glucosidase inhibitors and DPP IV inhibitors appear to be weight neutral. Thiazolidinediones cause weight gain via irreversible adipogenesis, but some in the class may reduce cardiovascular risk by shifting fat to the subcutaneous compartment and away from the abdominal compartment. Patients, nonetheless, find this weight gain troublesome. Finally, sufonylureas and insulin itself clearly cause weight gain and, in my opinion, should be utilized later in the management of the patient with type 2 diabetes.
Louis J. Aronne, MD, is Director, Comprehensive Weight Control Program
at New York Presbyterian Hospital/Weill Cornell Medical Center.
For more related articles, click Obesity Perspectives.