A 60-year-old man is evaluated during a routine office visit. He was diagnosed with type 2 diabetes mellitus 6 years ago. Medical history is significant for coronary artery disease, hypertension, hyperlipidemia, and biliary pancreatitis. Medications are lisinopril, metoprolol, metformin, aspirin, and atorvastatin.
On physical examination, other than a blood pressure of 152/91 mm Hg, the vital signs are normal. BMI is 27. The remainder of the examination is normal.
Laboratory studies show a HbA1c level of 8.2%.
Which of the following is the most appropriate treatment for this patient?
MKSAP Answer and Critique
The correct answer is A. Empagliflozin. This item is available to MKSAP 18 subscribers as item 25 in the Endocrinology and Metabolism section. More information about MKSAP 18 is available online.
The patient has uncontrolled diabetes in the setting of coronary artery disease, and empagliflozin is the most appropriate treatment. Empagliflozin increases excretion of glucose by the kidneys through inhibition of the sodium-glucose transporter-2 (SGLT2) receptors. Empagliflozin received approval from the FDA for patients with type 2 diabetes and established cardiovascular disease based upon the results of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME). This study demonstrated a reduction in the primary composite outcome (cardiovascular-related death, nonfatal myocardial infarction, nonfatal stroke) and all-cause mortality when empagliflozin was added to standard care versus placebo. Empagliflozin has the additional potential benefit of inducing weight loss and blood pressure lowering in this patient with overweight and uncontrolled hypertension.
Although the sulfonylurea, glipizide, could improve the patient's glycemic control, it has the potential side effect of weight gain; the combination of metformin plus an SGLT2 inhibitor is superior to metformin plus a sulfonylurea (mean between-group difference, 4.7 kg [CI, 4.4 to 5.0 kg]). The combination of metformin and an SGLT2 inhibitor reduces systolic blood pressure more than that of metformin and a sulfonylurea (between-group difference, 5.1 mm Hg [CI, 4.2 to 6.0 mm Hg]).
In patients with type 2 diabetes and cardiovascular risk factors, a significant reduction in the primary composite outcome (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and rates of cardiovascular death and all-cause mortality has also been associated with liraglutide. There have been postmarketing reports of fatal and nonfatal acute pancreatitis associated with liraglutide. While it is not known if liraglutide increases risk for development of pancreatitis in patients with a history of pancreatitis, many experts avoid its use in this patient population.
The dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin, could improve the patient's glycemic control; however, the combination of metformin and an SGLT2 inhibitor reduces systolic blood pressure more than metformin and a DPP-4 inhibitor (pooled between-group difference, 4.1 mm Hg [CI, 3.6 to 4.6 mm Hg]) and SGLT2 inhibitors reduced weight more than DPP-4 inhibitors (between group difference, 2.5 to 2.7 kg). There have been postmarketing reports of fatal and nonfatal acute pancreatitis associated with sitagliptin. While no causal relationship has been established, FDA labeling guidelines recommend that sitagliptin be used with caution in patients with a history of pancreatitis and some experts recommend against its use entirely in this population.
- Empagliflozin has been shown to reduce cardiovascular-related events and all-cause mortality in patients with type 2 diabetes mellitus and cardiovascular disease.