Position of Sulfonylureas in the Current ERA: Review of National and International Guidelines

Abstract

Sulfonylureas (SUs) are one of the commonly prescribed oral anti-hyperglycemic agents (AHA) in low- and middle-income countries (LMICs), either in combination with metformin therapy or alone. However, concern about cardiovascular safety has limited the use of SUs in the management of type 2 diabetes mellitus (T2DM). Additionally, lack of uniformity in the national and international guidelines regarding the positioning of SUs in the management of diabetes has also been reported. The objective of this review was to assess the various national and international guidelines on diabetes management and understand the recommendations specific to SUs in various scenarios. A total of 33 national and international guidelines on the management of T2DM published in English were evaluated. These guidelines have considered the latest evidence and suggest the use of certain second-generation SUs as second-line therapy or in combination with other AHAs in select population and specific scenarios. Identification of the appropriate population, classification based on underlying risk, thorough assessment of the comorbid conditions, and a step-wise approach for the selection of appropriate SUs is essential for the effective management of T2DM. Additionally, cost-to–benefit ratio should be considered, particularly in LMICs, and SUs could continue to play an important role in such settings.

Effect of the SARS-CoV-2 pandemic on metabolic control in patients with type 2 diabetes: a 5-year cohort follow-up managed by a dynamic multidisciplinary team in Northeastern Mexico

“…The ADA 2024 recommends the prescription of an additional medication to metformin to maintain HbA1c targets [ 37 ] which explains the increase of all hypoglycemic agents and long-acting insulin prescription. Conversely, while sulfonylureas persist as one of the most prescribed second-line agents, their usage is diminishing due to the emergence of new, beneficial, and safer treatment options for patients [ 38 ].…”

Post-transcriptional regulation of insulin mRNA storage by G3BP1/2+condensates in beta cells

“…Sulfonylureas, the oldest class of medications for the treatment of type 2 diabetes, akin to KCl treatment, induce membrane depolarization and insulin secretion by binding to the sulfonylurea receptor subunit on ATP-sensitive potassium channels (Costello et al 2024). Despite their insulin secretagogue activity, these drugs are now considered secondary line treatments due to their long-term detrimental effects on beta cell viability, as they stimulate the release of insulin, but not its biosynthesis (Mohan et al 2022). Furthermore, sulfonylureas have been linked to endoplasmic reticulum stress (Qian et al 2008), and increased ROS production, leading to oxidative stress (Tsubouchi et al 2004).…”

Sodium–Glucose Cotransporter 2 Inhibitors in Patients with Diabetes and Coronary Artery Disease: Translating the Benefits of the Molecular Mechanisms of Gliflozins into Clinical Practice

“…These drugs act by stimulating insulin secretion in a glucose-independent manner. They are a heterogeneous class of molecules with a different half-life and metabolism resulting in weight gain and accentuating the phenomenon of beta-cell depletion, leading to therapeutic failure more quickly than other drug classes [11]. They can cause hypoglycemia, and this peculiarity contraindicates their use in elderly patients in whom a hypoglycemic event could have significant and life-threatening consequences.…”