Diabetes
Rachel Balick
Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose transport 2 (SGLT2) inhibitors could improve care for a new patient population, according to researchers in an updated report on management of hyperglycemia in type 2 diabetes.
The takeaways
“To summarize [the updated recommendations] in a sentence, the GLP-1 receptor agonists and SGLT2 inhibitors are paradigm-shifting therapies in type 2 diabetes for patients with atherosclerotic vascular disease, heart failure, and chronic kidney disease,” said John Buse, MD, PhD, chief of the endocrinology division at the University of North Carolina School of Medicine in Chapel Hill. Buse is a primary author of “2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD),” which was published in Diabetes Care in December 2019.
GLP-1 receptor agonists seem to have the greatest benefits in patients for whom atherosclerotic cardiovascular disease is a major threat. SGLT2 inhibitors have the greatest evidence of benefits for patients with chronic kidney disease and heart failure with reduced ejection fraction.
The effect on patients
“It is exciting to consider the possibility of compelling indications for two classes of diabetes medications, but it is difficult to say how it will affect patients at this time,” said Erin Pauling, PharmD, clinical assistant professor of pharmacy practice at State University of New York (SUNY) at Binghamton. Pauling serves as coordinator of APhA’s Diabetes Management Special Interest Group.
SGLT2 inhibitors and GLP-1 receptor agonists are used frequently because of their positive effects on weight and low risk of hypoglycemia, so many patients are already taking these agents, said Pauling. But many patients who could benefit from use of these drugs can’t afford them or can’t take them because of adverse effects. “I imagine the effect on prescribing patterns will become larger as agents in these medication classes become available as generics.”
Still, it is significant that the benefits of SGLT2 inhibitors and GLP-1 receptor agonists extend to patients with high risk of cardiovascular disease (CVD), not just those with established CVD. In addition, new information is available that can help practitioners determine whether an SGLT2 inhibitor or GLP-1 receptor is preferred for various types of cardiovascular risk.
“Practitioners should anticipate the evolution of [type 2 diabetes management] therapy recommendations in patients with CVD as [cardiovascular outcomes trials] continue,” Pauling said.
Pharmacists on the team
“A lot of physicians are busy in their clinical practice and may miss the fact that their patient with diabetes has chronic kidney disease, cardiovascular disease, or heart failure,” Buse said.
“To the extent that pharmacists could help identify those people and call it out to the team to ensure that they receive the appropriate and potentially life-saving therapy, that would be a big plus.”
Diabetes care has become increasingly complex as the number of treatment options has expanded, increasing the need for team-based diabetes care for diabetes, he said. “Hopefully, more and more patients will have pharmacists as part of their health care team to help them manage the disease.”
Changes to consensus recommendations
ADA and EASD previously recommended that, for type 2 diabetes, established CVD was a compelling indication for treatment with a GLP-1 receptor agonist or SGLT2 inhibitor. ADA and EASD now further suggest the following:
General consideration
- In appropriate high-risk individuals with established type 2 diabetes, the decision to treat with a GLP-1 receptor agonist or SGLT2 inhibitor to reduce a major adverse cardiac event (MACE), hypertensive heart failure (hHF), cardiovascular (CV) death, or chronic kidney disease (CKD) progression should be considered independently of baseline A1C or individualized A1C targets.
- Providers should engage in shared decision-making about initial combination therapy in new-onset cases of type 2 diabetes.
GLP-1 receptor agonist recommendations
- For patients with type 2 diabetes and established atherosclerotic CVD (e.g., prior myocardial infarction, ischemic stroke, unstable angina with ECG changes, myocardial ischemia on imaging or stress test, or revascularization of coronary, carotid, or peripheral arteries) where MACE is the gravest threat, the level of evidence for MACE benefit is greatest for GLP-1 receptor agonists.
- To reduce risk of MACE, GLP-1 receptor agonists can also be considered in patients with type 2 diabetes without established CVD but with indicators of high risk—specifically, patients ages 55 years or older with coronary, carotid, or lower extremity artery stenosis of less than 50%; left ventricular hypertrophy; estimated glomerular filtration rate (eGFR) 60 mL min-1 [1.73 m]-2; or albuminuria.
SGLT2 inhibitor recommendations
- For patients with or without established atherosclerotic CVD but with reduced ejection fraction (HFrEF) (EF < 45%) or CKD (eGFR 30 to ≤ 60 mL min-1 [1.73 m]-2 or urine albumin-to-creatinine ratio [UACR] > 30 mg/g—particularly UACR > 300 mg/g), the level of evidence for benefit is greatest for SGLT2 inhibitors.
- SGLT2 inhibitors are recommended in patients with type 2 diabetes and heart failure—particularly those with HFrEF—to reduce hHF, MACE, and CV death.
- SGLT2 inhibitors are recommended to prevent the progression of CKD, hHF, MACE, and CV death in patients with type 2 diabetes with CKD.
- Patients with foot ulcers or who are at high risk for amputation should be treated with SGLT2 inhibitors only after careful shared decision-making focused on risks and benefits, along with comprehensive education on foot care and amputation prevention.