The availability of new drug classes has sparked a debate regarding the utility and viability of SUs as a therapeutic option with views on CV risks and hypoglycemia. However, this may hold true for older SUs due to their non-selective mechanisms of action.

Sulfonylurea has reigned over the other antidiabetic agents in diabetes management for over 40 years. The development of modern SUs that do not block ischemic preconditioning has rendered the University Group Diabetes Program (UGDP) controversy moot and preserved a place for SUs in the treatment of type 2 diabetes.

Modern SUs are proven to be effective, safe and well-tolerated in various clinical situations. Sulfonylurea, when compared to the other oral antidiabetic agents (OADs) has the highest efficacy in reducing HbA1c levels by up to 2%, moderate risk of hypoglycemia, neutral CV event and a cost-effect therapy. Sulfonylureas are also reported as the most cost-effective therapy compared to other OADs.

There have been several key studies advocating the superiority of SU, namely, the UKPDS trial which reported that intensive glucose therapy with the SU has reduced the risk of microvascular complications.

In a 10-year follow-up study of the trial, it was determined that SU maintained a risk reduction in microvascular, macrovascular and myocardial infarctions up to 9%. Similarly, the ADVANCE trial and ADVANCE-ON echoed the same results with the added benefit of renal outcomes. The trial showed that intensive glucose control strategically reduced HbA1c by 6.5% thereby reducing the risk of renal failure and nephropathy by 11% and 21%, respectively. TOSCA.IT and CAROLINA trial established the status of SU as an OAD with a safe CV profile with similar risk reduction in 3P-Mace and 3P-Mace with hospitalization. Meanwhile, CAROLINA study reassured that the use of SU leads to weight gain in the initial therapy, yet it is stabilized over the long-term, especially with glimepiride.

Also, the use of SU with metformin was reported to have negated the weight gain and hypoglycemia. In cases of elderly patients, people in Ramadan or patients diagnosed with CKD, gliclazide was a choice for reducing the risk of secondary failure and Hb1Ac. Hence, it can be confirmed that SU is an effective second-line agent for glycemic control for type 2 diabetes. The renaissance of SUs therapy might ensure that it remains the drug of choice for uncontrolled diabetes in the future with enough room for flexibility.