PHILADELPHIA — Although endocrinologists may routinely prescribe the newer classes of diabetes drugs approved for cardiovascular risk reduction, cardiologists and primary care providers should also consider using these agents for patients with type 2 diabetes and heart disease, according to a speaker here.
“Things have changed a lot in the last year and a half,” Ildiko Lingvay, MD, MPH, MSCS, associate professor of internal medicine at University of Texas Southwestern Medical Center, said during a presentation. “There has been some new history-setting here with the FDA approving two drugs that initially were approved for diabetes for meeting CV death [reduction outcomes] in the case of empagliflozin [Jardiance, Boehringer Ingelheim] and for major adverse cardiovascular events [reduction] in the case of liraglutide [Victoza, Novo Nordisk].
“It’s the first time now that we have a drug for diabetes that’s also used for cardiovascular disease or a cardiovascular drug that’s used for diabetes, whichever way you want to look at it,” she said.
The American Diabetes Association 2018 guideline recommends lifestyle modification and metformin as first-line therapies for disease management in patients with type 2 diabetes and established atherosclerotic cardiovascular disease and encourages incorporation of empagliflozin or liraglutide as a second-line agent. Although canagliflozin (Invokana, Janssen) is not currently indicated for reducing CV risk, the ADA suggests considering that agent as a second-line therapy based on drug-specific and patient factors, according to Lingvay.
Lingvay discussed prescribing liraglutide, in particular.
Providers should write a prescription for the drug, which comes in a pen device, and a separate prescription for 32-guage needles, according to Lingvay. She emphasized that the needles are very small and injection is “virtually painless” and certainly less painful than a fingerstick. Prescribers reluctant to instruct in proper injection technique can send patients to a pharmacist for direction, she said.
Liraglutide should be titrated at 0.6 mg per day for the first week, increased to 1.2 mg per day the second week, and held at 1.8 mg per day thereafter. Daily injection into the abdomen, thigh or arm can be done at any time during the day and does not depend on meal timing or other medications, according to Lingvay.
For patients who experience gastrointestinal side effects (nausea, vomiting, diarrhea, abdominal pain), Lingvay recommends eating smaller meals and stopping before feeling full. Slower titration may also help. These symptoms are typically transient, so prescribes should encourage patients to continue the drug for several weeks, at least, before giving up, she said. Gastroparesis is a contraindication.
Liraglutide may be combined with other medications, Lingvay said, but preemptively reducing insulin or sulfonylurea dose by 30% or more, depending on glycemic control, can help avoid hypoglycemia that may be an issue with those agents.
Potential serious side effects associated with liraglutide that were suggested in clinical trials, including pancreatitis, pancreatic cancer and medullary thyroid cancer, have not been confirmed in ongoing surveillance trials, Lingvay said.
“If you look at the big picture, on the upside you have cardiovascular event reduction in high-risk patients, glucose lowering, weight loss, blood pressure lowering, beneficial lipid profile, renal protection, very low risk of hypoglycemia, the convenience of not needing to dose adjust even for renal disease,” Lingvay said.
Downsides may include daily injection and gastrointestinal effects and asymptomatic elevations in pancreatic enzymes in some patients.
Remaining questions, Lingvay said, include whether GLP-1 receptor agonists will prove effective for primary CV prevention in patients with diabetes or for primary or secondary prevention in other populations, such as those with obesity or type 1 diabetes. – by Jill Rollet
Lingvay I. GLP-1RAs for cardiovascular disease: why and how. Presented at: Heart in Diabetes Clinical Education Conference; July 13-15, 2018; Philadelphia.
: Lingvay reports she received research grants from GI Dynamics, Merck, Novartis, Novo Nordisk and Pfizer; other research support from AstraZeneca, Boehringer Ingelheim, Novo Nordisk and Sanofi; and honoraria from AstraZeneca, Intarcia, NovoNordisk and Sanofi.