What is the role of sodium-glucose cotransporter type 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) in the treatment of glucose intolerance disorders?

Updated: Jun 28, 2019
  • Author: Samuel T Olatunbosun, MD, FACP, FACE; Chief Editor: George T Griffing, MD  more...
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Answer

The American College of Cardiology released expert consensus decision pathways on the use of two major new classes of diabetes drugs—sodium-glucose cotransporter type 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs)—for cardiovascular (CV) risk reduction in patients with type 2 diabetes (TD2) and atherosclerotic CV disease (ASCVD) in November 2018. [69, 70] The main focus of management is in the outpatient ambulatory setting.

The SGLT2 inhibitors appear to reduce major adverse CV events (MACE) and the risk of heart failure (HF) but increase the risk for genital mycotic infections, whereas GLP-1RAs offer reductions in MACE but are associated with transient nausea and vomiting. Both classes of agents have benefits in reducing blood pressure and weight, and they have a low risk for hypoglycemia.

For CV risk reduction, initiate agents with demonstrated CV benefit from either drug class at the lowest doses; no uptitration is necessary for SGLT2 inhibitors, whereas the GLP-1RAs should be slowly uptitrated (to avoid nausea) to the maximal tolerated dose.

At the initiation of an SGLT2 inhibitor or a GLP-1RA agent, clinicians should avoid hypoglycemia in patients by monitoring those with A1C levels near or below target, particularly when patients' existing diabetes therapies include sulfonylureas, glinides, or insulin.

In addition to reducing MACE and CV death, SGLT2 inhibitors are also suitable for preventing hospitalization for HF.

Empagliflozin is the preferred SGLT2 inhibitor based on the available evidence and overall benefit-risk balance.

Liraglutide should be the preferred agent among the GLP-1RAs for CV event risk reduction.

Two SGLT2 inhibitors (ie, canagliflozin, ertugliflozin) appear to be associated with an increased risk of amputation. It is unclear whether or not this is a class effect; therefore, clinicians should closely monitor patients on these agents who have a history of amputation, peripheral arterial disease, neuropathy, or diabetic foot ulcers.

Patients with T2D and clinical ASCVD on metformin therapy (or in whom metformin is contraindicated or not tolerated) should have an SGLT2 inhibitor or GLP-1RA with proven CV benefit added to their treatment regimen. For patients not on background metformin therapy, practitioners may use their clinical judgment to prescribe an SGLT2 inhibitor or GLP-1RA for CV risk reduction.

It appears reasonable to concomitantly use an SGLT2 inhibitor and a GLP-1RA with demonstrated CV benefit if clinically indicated, although such combination therapy has not been studied for CVD risk reduction.


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