Patients who have diabetes often have—and are often unaware they have—cardiovascular complications. These complications can change the trajectory of this disease and are costly for society. Selecting therapeutic interventions that can simultaneously address diabetes and cardiovascular concerns is sensible. Jessica L. Kerr, PharmD, CDE, who is Interim Associate Dean at the Office of Professional and Student Affairs and a Professor/Clinical Pharmacist at Southern Illinois University Edwardsville School of Pharmacy, presented information describing how to appropriately assess and manage patients who have diabetes and cardiovascular disease (CVD). She said that careful treatment choices make the most impact to improve outcomes.

Using a case-based approach, Dr. Kerr discussed the difficulty in managing diabetes in patients who have elevated glucose levels and are resistant to treatment. Many patients have concurrent CVD and diabetes. Hyperglycemia predisposes patients to proatherogenic mechanisms. Intracellular hyperglycemia can lead to advanced glycation end products. Once these end products form, they can alter extracellular and intracellular proteins and promote atherogenesis. The resultant “polyol pathway” is an extensive biochemical process that occurs even when patients are in normoglycemia.

The FDA has pressed the pharmaceutical industry to examine the safety of each new therapy for type 2 diabetes, asking manufacturers to specifically demonstrate that the therapy does not cause unacceptable increase in CVD. Subsequently, industry must design all phase 2 and phase 3 trials to include patients who have a high risk of cardiovascular events and enroll some patients who are elderly, have advanced disease, and are renally impaired. The so-called cardiovascular outcomes trials must look at 3 major points: stroke, cardiovascular mortality, and the incidence of myocardial infarction.

Dr. Kerr reviewed current evidence associated with glucoselowering products. She indicated that since 2013, results for the dipeptidyl-peptidase-4 inhibitors (DPP-4 inhibitors) have been available, and an ample number of trials have addressed the sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) and the glucagon-like peptide-1 (GLP-1) agonists. Clinicians are employing GLP-1 agonists and SGLT2 inhibitors more often because they have a proven ability to reduce cardiovascular risk.

Dr. Kerr mentioned that the American Diabetes Association 2018 Standards of Care now call for use of a glucose-lowering agent with cardiovascular benefit—the GLP-1 agonists and SGLT2 inhibitors—as second-line therapy in patients with type 2 diabetes (T2D) with established CVD who do not meet glycemic targets with lifestyle modification and metformin. She noted that the overall findings for DPP-4 inhibitors have deemed these medications to be cardiac neutral. Some trials suggest that specific DPP-4 inhibitors may increase risk of heart failure, but more information is needed. Clinicians need to assess the patient’s past history of pancreatitis, need for renal dosing, safety and effectiveness needs, and cardiovascular risk.

When discussing the SGLT2 inhibitors, Dr. Kerr indicated current data lean toward positive cardiac outcomes in the area of major adverse cardiac events and with beneficial data for patients with heart failure. Drugs in this class also tend to have beneficial effects for chronic kidney disease. Unfortunately, some specific SGLT2 inhibitors have been associated with an increased risk of amputation and bone loss. Points for clinician’s assessment include ensuring that patients are aware of the increased risk of diabetic ketoacidosis, genitourinary infections, and the need for concurrent blood pressure control and hydration. Here, too, clinicians need to assess the patient’s cardiac risk.

Dr. Kerr also covered the emerging data on GLP-1 agonists. GLP-1 and glucose insulinotropic peptide (GIP) are essential to glucose homeostasis. The incretin effect is the phenomenon that occurs after administration of oral glucose. Initially, insulin release increases, probably because of signals originating in the intestine at mealtime insulin release. In total, incretin hormones are believed to be responsible for up to 60% of postprandial insulin release. GLP-1 also inhibits gastric emptying, decreases appetite, inhibits glucagon secretion from pancreatic α-cells, and slows the rate of endogenous glucose production, thus leading to improved glycemic control in T2D. This drug class has been associated with weight loss and gastrointestinal adverse effects. GLP-1 agonists are contraindicated in patients with a personal or family history of medullary thyroid carcinoma.

One of Dr. Kerr’s strongest points was that clinicians need to look at the goals of care in collaboration with the patient. Looking at key patient characteristics to determine if the patient has contraindications to certain therapies is critical, as is determining whether the patient’s A1C will respond appropriately to the medication under consideration. The patient’s target A1C is very important, especially if hypoglycemia is a significant concern. She encouraged audience members to use motivational interviewing techniques with patients so that patients can create solutions to their own problems. Helping patients identify all options and select the actions they are most likely to pursue increases adherence rates.

Dr. Kerr described the ETAC method, which addresses efficacy, toxicity, adherence and adverse events, and costs and contraindications. She summarized implications for pharmacists and pharmacy staff beautifully, emphasizing that clinical inertia must be addressed early. Pharmacists are lead educators and can promote evidence-based medication practices. Most importantly, pharmacists can involve patients in their own decision making, and both pharmacists and patients can become valuable members of the diabetes care team.