A 54-year-old man comes to the office for diabetes follow-up. The patient has a 5-year history of type 2 diabetes mellitus treated with metformin. He also has hypertension and had coronary stenting for non-ST-elevation myocardial infarction a month ago. The patient feels well and reports no symptoms. Since the myocardial infarction, he has taken all medications as prescribed and strictly followed lifestyle recommendations. He does not use tobacco, alcohol, or illicit drugs. Blood pressure is 130/74 mm Hg and pulse is 68/min. BMI is 30 kg/m². Physical examination shows no abnormalities. Serum creatinine is 0.8 mg/dL and hemoglobin A1c is 7.8%. Which of the following medications has an added protective effect on this patient's cardiac and weight-related comorbidities?

Question

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Explanation: 11ec25c8_d3a9_570f_bc81_29a540432ec0_MD0003_00 Despite following lifestyle recommendations and taking metformin (first-line medication for type 2 diabetes mellitus), this patient has poor glycemic control (hemoglobin A1c >7%), placing him at increased risk of macrovascular and microvascular complications. Therefore, add-on therapy (metformin + another medication) is indicated, the choice of which should be dictated by the patient's comorbid conditions. Given this patient's established coronary artery disease (recent non-ST-elevation myocardial infarction with stenting) and obesity (BMI ≥30 kg/m²), an SGLT-inhibitor (eg, canagliflozin, empagliflozin) is an optimal choice. ² Recommended add-on therapy for patients with established cardiovascular disease (eg, heart failure, myocardial infarction, coronary artery disease) includes the following: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors (eg, canagliflozin, empagliflozin), which cause increased urinary excretion of sodium and glucose. These agents induce weight loss and decrease risk of cardiovascular mortality. They also slow progression of albuminuria. Major adverse effects include genitourinary infections and euglycemic ketoacidosis. Glucagon-like peptide-1 (GLP-1) receptor agonists (eg, semaglutide, liraglutide), which are given by injection and regulate glucose by slowing gastric emptying, suppressing glucagon secretion, and increasing glucose-dependent insulin release. Similar to SGLT-2 inhibitors, GLP-1 agonists reduce cardiovascular mortality and induce significant weight loss. Major adverse effects include gastrointestinal disturbances (eg, nausea, abdominal pain) and, rarely, pancreatitis. (Choices A and C) Sulfonylureas (eg, glipizide) stimulate endogenous pancreatic insulin secretion. Like insulin, they are associated with weight gain (due to insulin-induced anabolic effects) and increased risk of hypoglycemia. Neither insulin nor sulfonylureas have been shown to reduce cardiovascular mortality or morbidity. (Choice D) Thiazolidinediones (eg, pioglitazone), which decrease gluconeogenesis and improve insulin sensitivity, are associated with weight gain and fluid retention. In particular, these agents have been linked to increased risk of heart failure and would not be appropriate for this patient with established coronary artery disease. (Choice E) Dipeptidyl peptidase-4 inhibitors (eg, sitagliptin) have a mechanism of action similar to that of GLP-1 agonists; however, unlike GLP-1 agonists, they are not cardioprotective and are weight-neutral. Educational objective: Add-on therapy in type 2 diabetes mellitus for patients with established cardiovascular disease includes glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, which reduce cardiovascular mortality and morbidity. Both agents are associated with weight loss, an effect not seen with insulin, sulfonylureas, and thiazolidinediones. References: SGLT2 inhibitors with cardiovascular benefits: transforming clinical care in type 2 diabetes mellitus. (http://www.ncbi.nlm.nih.gov/pubmed/29196150)

A 54-Year-Old Man Comes to the Office for Diabetes Follow-Up