Cardiovascular Benefits of Pharmacotherapies for Type 2 Diabetes

SOURCE: Yandrapalli S, et al. Cardiovascular benefits and safety of non-insulin medications used in the treatment of type 2 diabetes mellitus. Postgrad Med 2017;129:811-821.

The primary goals of diabetes management are reductions in microvascular endpoints (retinopathy, neuropathy, nephropathy), macrovascular endpoints (myocardial infarction, stroke), and improved quality of life (less dry mouth, urinary frequency, visual disturbance). In the most recent decade, the FDA has mandated that new pharmacologic entities for management of glucose in type 2 diabetes (T2DM) establish cardiovascular (CV) safety with a substantial clinical trial. As a result, there are now several agents that have shown not only CV safety in T2DM, but also actual reductions in CV endpoints.

The three agents with FDA labeling for CV risk reduction based on their successful clinical trials are empagliflozin (EMPA-REG), canagliflozin (CANVAS), and liraglutide (LEADER). Another glucagon-like peptide-1 receptor agonist, semaglutide, has been approved for treatment of T2DM. It demonstrated CV risk reduction in a recent clinical trial (SUSTAIN), but does not yet carry FDA labeling for CV risk reduction.

The most recent American Diabetes Association 2018 guidance for pharmacotherapy of T2DM suggests that for patients with existing CV disease who are uncontrolled on metformin and lifestyle, consideration should be given to prioritizing agents demonstrated to provide CV risk reduction (empagliflozin, liraglutide, and canagliflozin).

The Vagaries of Reported Penicillin Allergy

SOURCE: Sundquist BK, et al. Proactive penicillin allergy testing in primary care patients labeled as allergic: Outcomes and barriers. Postgrad Med 2017;129:915-920.

I am allergic to penicillin, or at least that’s what I say in healthcare settings when someone asks. My designation as penicillin allergic occurred around age 5 when I developed a rash after a shot of penicillin. The malady I was suffering was called “a respiratory infection,” with the subsequent all-encompassing remedy supplied: a shot of penicillin (at least that’s how it was in 1951). I am told that within the next day or two I developed a rash, and was told to eschew penicillin.

But was I really allergic? Certainly, there are many commonplace viral upper respiratory illnesses afflicting youngsters that can manifest a rash. Subsequently, I have received cephalosporins uneventfully. The literature says that > 90% of patients who report a history of penicillin allergy can tolerate penicillin. Unstimulated penicillin sensitivity wanes over time: By age 10 years, 80% of allergic subjects are no longer allergic.

Sundquist et al recruited patients with a history of penicillin allergy. Skin testing in 37 subjects (prick testing and intradermal testing) identified none as allergic; subsequent oral challenge also demonstrated no positive results. The authors suggested that good antibiotic stewardship supports consideration of clarification of whether patients who report penicillin allergy are allergic. Numerous infectious diseases are best served by penicillin treatment for the sake of cost considerations, specificity, and antibiotic stewardship.

Osteoblast Modulation in Osteoporosis Treatment

SOURCE: Corrado A, et al. Osteoblast as a target of anti-osteoporotic treatment. Postgrad Med 2017;129:858-865.

In healthy bones, osteoclast activity is balanced with osteoblast activity to produce a continuing stream of freshly created bone by degradation of aging bone and replacement with new bone. After attainment of the peak level of mature bone in early adulthood, osteoclast activity modestly exceeds osteoblast activity, leading to a gradual decline in bone mineral density that we call age-related bone loss to distinguish it from the more rapid bone loss seen at menopause (regardless of age) due to estrogen loss that characteristically outpaces simple age-related bone loss.

Most pharmacologic interventions currently in use for treatment or prevention of osteoporosis rely on osteoclast inhibition to enhance (or at least maintain) bone mineral density. In contrast, teriparatide primarily works by stimulation of osteoblasts. Estrogen also produces some positive activity on osteoblasts, such as inhibition of osteoblast apoptosis. Finally, even though the primary mechanism of bisphosphonates is inhibition of osteoclastic activity, even this pharmacologic class produces some favorable effects on osteoblasts.

One additional class of pharmacologic agent has shown promising effects: The anti-sclerostin antibody agent romosozumab provides both stimulation to osteoblasts and diminution of osteoclast activity. This agent is pending FDA approval.