Treatment of Type 2 Diabetes in Subjects with Obesity: What is the Best Approach?

Abstract

Prevalence of both obesity and type 2 diabetes (T2DM) is increasing worldwide. Obesity, along with insulin resistance, predisposes individuals to low-grade chronic inflammation. Moreover, the combination of insulin resistance and hyperinsulinemia gives rise to the metabolic syndrome. The management of obesity can delay the progression to diabetes and first line treatment is represented by interventions on lifestyle (low-calorie diet and aerobic exercise). In obese patients with T2DM, weight loss improves glycaemic control and, therefore, reduces the antidiabetic drug need. While some older medications, including insulin, result in weight gain, the new molecules (glucagon-like peptide receptors agonists [GLP-1ra] and sodium-glucose co-transporter 2 inhibitors [SGLT2i]) result in weight loss. GLP-1ra has an anorexic action because it slows emptying gastric, whereas SGLT2i induce glycosuria by an osmotic diuresis associated with a loss of water. To date, metformin is used as a first-line anti-diabetic drug. This molecule is known to reduce hepatic gluconeogenesis, to decrease intestinal absorption of glucose and to improve peripheral glucose uptake. In obese patients with insulin resistance metformin can correct this alteration and promote weight loss. the same disease, the metabolic syndrome. Metformin is the first-line therapy in T2DM for its tolerability and efficacy in reducing glycated hemoglobin. Thanks to their different mechanism of action, metformin in association with GLP-1ra and/or SGLT2i probably represent the best choice for obese patients with T2DM.