Physiologic and weight-focused treatment strategies for managing type 2 diabetes mellitus: the metformin, glucagon-like peptide-1 receptor agonist, and insulin (MGI) approach.

The prevalence of type 2 diabetes mellitus (T2DM) is rising in association with an increase in obesity rates. Current treatment options for patients with T2DM include lifestyle modifications and numerous antidiabetic medications. Despite the availability of effective and well-tolerated treatments, many patients do not achieve recommended glycemic targets. Lack of efficacy is complicated by the wide range of available agents and little specificity in treatment guidelines, thus challenging clinicians to understand the relative benefits and risks of individual options for each patient. In this article, lifestyle intervention strategies and current antidiabetic agents are evaluated for their efficacy, safety, and weight-loss potential. Because of the heterogeneous and progressive nature of T2DM, physicians should advocate approaches that emphasize weight management, limit the risk of hypoglycemia and adverse events, and focus on the core pathophysiologic defects in patients with T2DM. A healthy, plant-based diet that is low in saturated fat and refined carbohydrates but high in whole grains, vegetables, legumes, and fruits, coupled with resistance and aerobic exercise regimens, are recommended for patients with T2DM. When necessary, drug intervention, described in this article as the MGI (metformin, glucagon-like peptide-1 receptor agonist, and insulin) approach, should begin with metformin and progress to the early addition of glucagon-like peptide-1 receptor agonists because of their weight loss potential and ability to target multiple pathophysiologic defects in patients with T2DM. For most patients, treatments that induce weight gain and hypoglycemia should be avoided. Long-acting insulin should be initiated if glycemic control is not achieved with metformin and glucagon-like peptide-1 receptor agonist combination therapy, focusing on long-acting insulin analogs that induce the least weight gain and have the lowest hypoglycemic risk. Ultimately, a patient-centered treatment approach that addresses the core pathologies of T2DM and obesity will not only increase overall efficacy and the likelihood that a patient adheres to treatment, but may also improve a patient's mental well-being and quality of life.