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    The OD’s role with new diabetes drugs

    Stay in the know with new treatment options to preserve your patients’ sight

    Ever since the oral diabetes medication rosiglitazone (Avandia, GlaxoSmithKline) was found to increase the risk of congestive heart failure by several analyses after U.S. Food and Drug Administration (FDA) approval, the FDA has required all new diabetes medications to not only demonstrate clinically meaningful reductions in blood glucose but also undergo more rigorous cardiovascular (CV) outcomes safety trials.1

    Consequently, a number of new agents have been found to decrease the risk of mortality in general and CV mortality in particular.2 A reduction in major adverse cardiovascular events (MACE), including heart attack, stroke and hospitalization for congestive heart failure (CHF), has also accompanied the introduction of some medications per recent findings.3

    Previously from Dr. Chous: New strategies to assess the risk of diabetes-related vision loss

    It is important for eyecare providers to be familiar with these new drugs and findings. We often see patients with diabetes, metabolic syndrome, and high CV risk, and we are in a position to help counsel our patients about new treatments—and even suggest that appropriate patients have conversations with their primary-care physicians, endocrinologists and cardiologists.

    GLP-1 analogs

    Glucagon-like peptide-1 (GLP-1) analogs are drugs that mimic the action of their namesake gut-derived protein secreted when food passes through the terminal ileum of the small intestine. GLP-1 has multiple effects on blood glucose, causing a short-term release of endogenous insulin from functioning pancreatic beta cells as well as suppressing glucagon by pancreatic alpha cells and appetite by affecting hypothalamic satiety receptors.4

    Evidence shows that GLP-1 production is lost in type 2 diabetes and that injectable GLP-1 analogs like exenatide (Byetta and Bydureon, AstraZeneca), liraglutide (Victoza, Novo Nordisk), and dulaglutide (Trulicity, Lilly) lower glycosylated hemoglobin and assist with weight loss.5

    Related: How diabetes is linked to gut bacteria

    The LEADER Trial showed that adding liraglutide reduced the risk of MACE and cardiovascular mortality by 13 percent and 22 percent, respectively, compared to standard care.6 Though retinopathy rates were not significantly different, the risk of diabetic nephropathy was reduced by 22 percent in the liraglutide treatment arm.

    Of interest, an extended release GLP-1 analog (semiglutide) awaiting FDA approval also has been associated with reduced cardiovascular (CV) risk but worsening diabetic retinopathy in patients with poor HbA1c at baseline and who achieved significant reductions in mean blood glucose (> 1.8 point drop in HbA1c). This phenomenon is also seen with insulin therapy and attributed to the so-called “glycemic re-entry effect” rather than the drug molecule itself.7,8

    SGLT2 inhibitors

    Sodium glucose transporter-2 reuptake (SGLT2) inhibitors are novel drugs that block normal reabsorption of serum glucose at the proximal renal tubule, allowing increased urinary excretion of glucose and osmotic diuresis.9

    These drugs decrease blood pressure and arterial stiffness, assist with weight loss, and have shown benefit in early- (but not late-) stage diabetic kidney disease.10

    Three agents are currently available: canagliflozin (Invokana, Janssen), dapagliflozin (Farxiga, AstraZeneca) and empagliflozin (Jardiance, Lilly).

    The EMPA-Reg trial conducted in Europe showed a 38 percent reduction in mortality and a 35 percent reduction in hospitalization for congestive heart failure with empagliflozin compared to usual care.11


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