SGLT2 Inhibitors and GLP-1 Receptor Agonists: Indications

Brown E, Heerspink HJ, Cuthbertson DJ, Wilding JP.
SGLT2 Inhibitors and GLP-1 Receptor Agonists: Established and Emerging Indications. Lancet 2021;Jun 30:[Epub ahead of print].

The following are key points to remember from a review article about established and emerging indications for sodium-glucose luminal cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists:

  1. SGLT2 inhibitors are a group of oral medications, whereas GLP-1 receptor agonists are generally injectable therapies. Oral semaglutide is the first oral GLP-1 receptor agonist available.
  2. SGLT2 inhibitors and GLP-1 receptor agonists are used in patients with type 2 diabetes as glucose-lowering therapies, with additional benefits of weight loss and blood pressure reduction.
  3. Data from cardiovascular outcome trials have highlighted that these drugs confer protection against major cardiovascular disease in those with established atherosclerotic cardiovascular disease, reduce the risk of admission to hospital for heart failure, and reduce cardiovascular and all-cause mortality.
  4. When used for glucose lowering, SGLT2 inhibitors are most effective if the estimated glomerular filtration rate is >60 ml/min/1.73 m2 at initiation and should be avoided where there is a risk of diabetic ketoacidosis.
  5. These drugs are now second-line, or even first-line, glucose-lowering therapies in patients with cardiorenal disease, irrespective of glycemic control.
  6. If an SGLT2 inhibitor or GLP-1 receptor agonist is considered suitable in patients with type 2 diabetes, treatment should be prioritized according to existing evidence: GLP-1 receptor agonists should be considered in patients at a high risk of, or with established, cardiovascular disease and SGLT2 inhibitors considered for patients with heart failure (with reduced ejection fraction) or chronic kidney disease (with or without established cardiovascular disease).
  7. There are now compelling data on the benefits of these drugs for a range of other clinical indications even without type 2 diabetes, including for GLP-1 receptor agonists in patients with obesity and overweight with weight-related comorbidities.
  8. SGLT2 inhibitors are contraindicated in pregnancy (reproductive toxicity in animal studies) and breastfeeding (data from few animal studies only). GLP-1 receptor agonists are contraindicated in pregnancy and breastfeeding (based on few animal studies only) and a personal or family history of multiple endocrine neoplasia type 2 or medullary thyroid cancer.
  9. Clinicians should ensure that retinopathy screening is done before initiation of GLP-1 receptor agonists (for semaglutide only).
  10. Ongoing studies are evaluating the cardiorenal benefits of SGLT2 inhibitors and GLP-1 receptor agonists in different populations. Evidence regarding combination therapy with SGLT2 inhibitors and GLP-1 receptor agonists will also continue to add to this data-rich, rapidly evolving, therapeutic area.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Lipid Metabolism, Acute Heart Failure

Keywords: Blood Pressure, Breast Feeding, Diabetes Mellitus, Type 2, Diabetic Ketoacidosis, Glomerular Filtration Rate, Glucagon-Like Peptide 1, Glucose, Heart Failure, Metabolic Syndrome, Myocardial Ischemia, Obesity, Overweight, Pharmaceutical Preparations, Pregnancy, Primary Prevention, Renal Insufficiency, Chronic, Retinal Diseases, Sodium-Glucose Transporter 2, Thyroid Neoplasms, Weight Loss

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