title: Combating the dual burden: therapeutic targeting of common pathways in obesity and type 2 diabetes.
abstract: The increasing prevalence of obesity is contributing substantially to the ongoing epidemic of type 2 diabetes. Abdominal adiposity, a feature of ectopic fat syndrome, is associated with silent inflammation, abnormal hormone secretion, and various metabolic disturbances that contribute to insulin resistance and insulin secretory defects, resulting in type 2 diabetes, and induce a toxic pattern that leads to cardiovascular disease, liver pathologies, and cancer. Despite the importance of weight control strategies in the prevention and management of type 2 diabetes, long-term results from lifestyle or drug interventions are generally disappointing. Furthermore, most of the classic glucose-lowering drugs have a side-effect of weight gain, which renders the management of most overweight or obese people with type 2 diabetes even more challenging. Many anti-obesity pharmacological drugs targeting central control of appetite were withdrawn from the market because of safety concerns. The gastrointestinal lipase inhibitor orlistat was the only anti-obesity drug available until the recent US, but not European, launch of phentermine-controlled-release topiramate and lorcaserin. Improved knowledge about bodyweight regulation opens new prospects for the potential use of peptides derived from the gut or the adipose tissue. Combination therapy will probably be necessary to avoid compensatory mechanisms and potentiate initial weight loss while avoiding weight regain. New glucose-lowering treatments, especially glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors, offer advantages over traditional antidiabetic drugs by promoting weight loss while improving glucose control. In this Review, we explore the overlapping pathophysiology and also how various treatments can, alone or in combination, combat the dual burden of obesity and type 2 diabetes.
authors.affiliation: University of Liège, Division of Diabetes, Nutrition and Metabolic Disorders and Clinical Pharmacology Unit, CHU Sart Tilman, Liège, Belgium. Electronic address: andre.scheen@chu.ulg.ac.be.
authors.forename: André J
authors.initials: AJ
authors.lastname: Scheen
authors.affiliation: University of Antwerp, Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Antwerp, Belgium.
authors.forename: Luc F
authors.initials: LF
authors.lastname: Van Gaal
mesh_terms: D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology* / Q000503:physiopathology; D019468:Disease Management; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D009765:Obesity / Q000188:drug therapy* / Q000453:epidemiology* / Q000503:physiopathology
chemical_list: D019440:Anti-Obesity Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents