Should Sulfonylureas Remain an Acceptable First-Line Add-on to Metformin Therapy in Patients With Type 2 Diabetes? Yes, They Continue to Serve Us Well!

Abstract

Since their introduction to clinical practice in the 1950s, sulfonylureas have been widely prescribed for use in patients with type 2 diabetes. Of all the other medications currently available for clinical use, only metformin has been used more frequently. However, several new drug classes have emerged that are reported to have equal glucose-lowering efficacy and greater safety when added to treatment of patients in whom metformin monotherapy is no longer sufficient. Moreover, current arguments also suggest that the alternative drugs may be superior to sulfonylureas with regard to the risk of cardiovascular complications. Thus, while there is universal agreement that metformin should remain the first-line pharmacologic therapy for those in whom lifestyle modification is insufficient to control hyperglycemia, there is no consensus as to which drug should be added to metformin. Therefore, given the current controversy, we provide a Point-Counterpoint on this issue. In the point narrative presented below, Dr. Abrahamson provides his argument suggesting that avoiding use of sulfonylureas as a class of medication as an add-on to metformin is not appropriate as there are many patients whose glycemic control would improve with use of these drugs with minimal risk of adverse events. In the following counterpoint narrative, Dr. Genuth suggests there is no longer a need for sulfonylureas to remain a first-line addition to metformin for those patients whose clinical characteristics are appropriate and whose health insurance and/or financial resources make an alternative drug affordable. —William T. Cefalu Editor in Chief, Diabetes Care

Effect of antihyperglycemic drug monotherapy to prevent the progression of mild hyperglycemia in early type 2 diabetic patients: the Japan Early Diabetes Intervention Study (JEDIS)

“…After the start of gliclazide (SU), HbA1c decreased temporarily but after 6 M it returned to the baseline level and increased further thereafter. The decrease of BW was minimal in arm SU as compared to other arms, suggesting a distinct effect of SU on body weight [28,46,47]. There was also the concern on hypoglycemia to use drugs in an early stage of T2DM, especially for SU drug [54], and we thought that physicians in charge may have hesitated to dose up gliclazide sufficiently [47].…”

“…At the same time, in JEDIS-2, DPP-4 is i.e., sitagliptin and vildagliptin were additionally adopted as an another arm of pharmacologic treatment (DPP-4i arm as group D), as they became commercially available and getting popular in Japan at the end of 2009. In this occasion, gliclazide drug (arm SU) was omitted out of JEDIS-2, because its risk to induce severe hypoglycemia or weight gain was seriously concerned in practice, as often discussed in some articles [46,47].…”

Tratamento do Diabetes Melito Tipo 2: Ainda Existe Lugar Para as Sulfonilureias?

“…Vários aspectos, porém, precisam ser lembrados antes de considerá-las uma classe terapêutica obsoleta, com relação risco-benefício desfavorável, e esse impasse parece estar longe de ser resolvido. 20,21 …”

Comparative Effectiveness of Insulin versus Combination Sulfonylurea and Insulin: a Cohort Study of Veterans with Type 2 Diabetes

“…This could be due to ease of regimen initiation (no titration usually needed), providers' preference or contraindications to metformin use (e.g., patients with impaired kidney function due to concerns for lactic acidosis). [2][3][4][5][6] Although the optimal strategy to intensify initial sulfonylurea monotherapy remains unclear, experts have recommended that intensification may be accomplished by insulin as add-on therapy or insulin monotherapy. [7][8][9] However, evidence comparing important clinical outcomes between these specific intensification regimens is lacking.…”