The composite risk of cardiovascular events and hospitalization for HF was similar for patients with history of HF compared with patients without a history of HF with the use of saxagliptin.173 A recent meta-anal- ysis of available studies suggests that DPP-4 inhibitor use is associated with an increased risk of HF, without any clear evidence of differences among drugs of that Additional studies are being conducted to as- sess the cardiovascular efficacy of DPP-4 inhibitors and GLP-1 based therapies, with HF being measured as a secondary outcome. These studies may provide insights into the safety and efficacy of incretin-based therapies with primary outcomes of HF, especially in patients with diabetes mellitus and established HF. Many patients with diabetes mellitus and HF will require insulin therapy either as monotherapy or in combination with other agents to achieve adequate glycemic control. Insulin is associated with hypoglycemia and weight gain. Some observational studies have demonstrated that in- sulin use may be associated with a greater risk of devel- oping incident HF in patients with diabetes mellitus.175 In diabetic patients with established HF, observational studies have also demonstrated an association between insulin use and increased mortality,114,176,177 although these findings are potentially limited by unmeasured confounding factors, and not all observational studies have demonstrated this increased hazard.140 Given that individuals who require insulin for type 2 diabetes mel- litus are more likely to have a longer diabetes mellitus duration and severity, the use of insulin may be a marker of more advanced disease and a high-risk group rather than a direct contributor to increased HF events and in- creased mortality in patients with HF. 