Patients with type 2 diabetes, approximately 85% of whom are overweight or obese, often have an increased incidence of cardiovascular disease (CVD) risk factors such as hypertension and dyslipidemia. Both type 2 diabetes and obesity are independent risk factors for CVD. Unfortunately, many therapies aimed at maintaining and improving glucose control are associated with weight gain. Among the older antidiabetes agents, most, including the insulin secretagogues and sensitizers, can lead to weight gain, except for metformin, which is weight-neutral. Among the newer agents, the dipeptidyl peptidase-4 inhibitors generally are weight-neutral in addition to lowering glucose, while the glucagon-like peptide-1 receptor agonists lead to weight reduction. Patients with type 2 diabetes are at an increased risk for both diabetes- and CV-related outcomes, and weight reduction is an important component of diabetes management. Weight gain in patients with type 2 diabetes can contribute to patient frustration and may negatively impact their compliance to therapeutic regimens. The selection of antidiabetes agents that not only improve glucose control but reduce or have a neutral effect on weight with beneficial effects on lipids are ideal options for managing patients with type 2 diabetes.