Study Highlights

• This expert opinion from a European Consensus Panel summarized current local treatment guidelines in European countries, which vary widely among countries regarding sulfonylurea use in type 2 diabetes.
• Sulfonylureas are often suggested as second-line treatment after metformin and are often ranked equally with newer glucose-lowering medications.
• Advantages of sodium-glucose cotransporter type 2 inhibitors and glucagon-like peptide-1 receptor agonists, based on strong evidence, include low hypoglycemia risk, enhanced weight loss, and a positive effect on vascular, cardiac, and renal endpoints.
• Using sulfonylurea instead of SGLT2 inhibitors and GLP-1 receptor agonists may therefore deprive patients of these benefits, including potentially important cardiorenal effects.
• For patients with known cardiovascular disease or who are at very high cardiovascular risk, diabetes management should include use of SGLT2 inhibitors and/or GLP-1 receptor agonists in the absence of contraindications.
• In resource-constrained settings, however, routine use of sulfonylureas as second-line agents is still acceptable.
• On the basis of the available evidence, the experts made 3 recommendations regarding sulfonylurea use.
• Because the leading priority in type 2 diabetes treatment is to improve overall outcomes, including cardiovascular and renal events and survival, newer diabetes medications should be preferred over sulfonylureas as second-line glucose-lowering medications.
• These preferred medications are SGLT2 inhibitors, GLP-1 receptor agonists, and to a lesser extent, DPP-4 inhibitors.
• Rationale for this recommendation includes the minimal hypoglycemic risk associated with their use, their positive (GLP-1 receptor agonists, SGLT2 inhibitors) or neutral (DPP-4 inhibitors) cardiovascular effects, their positive renal effects (SGLT2 inhibitors >> GLP-1 receptor agonists > DPP-4 inhibitors), their neutral (DPP-4 inhibitors) or positive (GLP-1 receptor agonists, SGLT2 inhibitors) effects on body weight, possibly longer glycemic durability, and ease of use, with less need for titration and self-monitoring of blood glucose.
• Newer diabetes agents might be preferable in all patients with type 2 diabetes and without specific contraindications to their use.
• In patients with known cardiovascular disease or who are at very high cardiovascular risk, SGLT2 inhibitors and/or GLP-1 receptor agonists should be used as part of the diabetes treatment regimen unless there are contraindications.
• Use of sulfonylureas is not known to be associated with increased cardiovascular risk, but there is no evidence for improved cardiovascular and renal risk in patients with type 2 diabetes treated with sulfonylureas.
• As per the American Diabetes Association Standards of Care, routine use of sulfonylureas as second-line agents might be acceptable in resource-constrained settings and in the short term.
• When sulfonylureas are prescribed, gliclazide may be the preferred agent and clinicians should consider patient education on hypoglycemia and self-monitoring of blood glucose.
• Given the body of evidence regarding the benefits of SGLT2 inhibitors and GLP-1 receptor agonists on vascular, cardiac, and renal endpoints, use of sulfonylureas instead of SGLT2 inhibitors and GLP-1 receptor agonists needs a strong and well-supported motivation, as it may deprive the patient of possibly important cardiorenal protection.
• In terms of specific recommendations for sulfonylurea use, the experts suggested sulfonylurea monotherapy only when metformin, SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, and pioglitazone are contraindicated, not tolerated, unavailable, or not affordable.
• When these 4 newer agents are suitable, sulfonylureas should be considered the last option among second-line drugs, even as a part of dual combination therapy, because of the risk for hypoglycemia and weight gain, less durability, need for titrations, and self-monitoring of blood glucose in some countries.
• To intensify dual therapy, clinicians may consider sulfonylureas in triple-combination therapy when needed to improve HbA1c, primarily to achieve microvascular protection, but newer agents are preferred when suitable.
• Adding sulfonylurea to metformin plus SGLT2 inhibitors plus GLP-1 receptor agonists, or to metformin plus DPP-4 inhibitors plus SGLT2 inhibitors, might help lower HbA1c for purposes of microvascular protection.
• Sulfonylureas should not be used in patients who use insulin, especially in those receiving intensified insulin regimens, because of the multiplicative risk for hypoglycemia and the absence of a dedicated trial showing additional benefit.
• Sulfonylureas should be used with extreme caution in the elderly because of higher risk for prolonged, severe hypoglycemia; less concern regarding microvascular risk; and lack of protection from cardiovascular events by glucose control with sulfonylureas.
• Sulfonylureas should be used with great caution in patients with chronic kidney disease because of overexposure and greater risk for hypoglycemia, but they are not contraindicated in patients with cardiovascular disease.
• If hypoglycemia is detected during sulfonylurea treatment, the sulfonylurea should be discontinued or titrated down.
• Many drug-related factors govern the choice of glucose-lowering medications: effects on blood glucose, body weight, cardiovascular and renal outcomes; risk for hypoglycemia; renal clearance; durability of the blood glucose lowering effect; mechanism of action, such as need for residual beta cell function; ease of use, with need for titration and/or self-monitoring of blood glucose; and adverse effects.
• Clinicians should balance these factors and patient preferences against costs while considering local regulations governing reimbursement and international guidelines, all of which change rapidly and vary among different countries, regions, and specialist groups.
• Cost considerations should include not only the acquisition costs of glucose-lowering medications but also the direct and indirect costs related to acute and chronic complications, such as dialysis, foot disease, and cardiac complications.
• Although sulfonylureas are inexpensive and effectively lower blood glucose, their use is associated with hypoglycemia and weight gain.
• Hypoglycemia is associated with poorer quality of life, increased risk for falls and coma, loss of confidence in treatment, increased healthcare costs, and loss of working days.