To prevent hypoglycemia, Discontinue sulfonylureas once insulin is initiated: ADA and EASD's Consensus update

USA: Agents such as sulfonylureas that cause hypoglycemia in themselves should be discontinued once insulin is initiated, a recent consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) has stated.

It also emphasizes that fasting may increase hypoglycemia rates in those treated with sulfonylureas and insulin, underscoring the requirement for individualized education and proactive medication management during significant dietary changes. Further, it states that If sulfonylureas or insulin are used, less stringent targets should be considered in such settings and de-prescribing if asymptomatic or severe hypoglycemia ensues.

The report by ADA and EASD on hyperglycemia management was presented at the 58th EASD Annual Meeting in Stockholm, Sweden, and subsequently published in the journals Diabetologia and Diabetes Care.

Previous consensus and reports have suggested that sulfonylureas have high glucose-lowering efficacy inexpensive and accessible, but lack durable effect. 

The document further stated that due to their glucose-independent stimulation of insulin secretion, they are associated with an increased hypoglycemia risk. Also, sulfonylureas are associated with weight gain, which is relatively modest in large cohort studies. The authors noted that there is no difference in the incidence of MACE among people at high cardiovascular risk treated with glimepiride or linagliptin. 

About Sulfonylureas 

Until metformin approval, sulfonylureas (SU) were the only approved insulin competitors and were used extensively for the treatment of type 2 diabetes mellitus (T2DM). Only three SU drugs are currently available for prescription (glipizide, glyburide, and glimepiride). 

Glyburide/metformin and glipizide/metformin are the two SU and metformin combination regimens that have been FDA approved and are currently marketed. 

They exhibit their mechanism of action by binding to and closing ATP-sensitive K+ (KATP) channels on the cell membrane of pancreatic beta cells which results in cell depolarization preventing the exit of potassium. The depolarization results in opening the voltage-gated Ca2+ channels. The increase in intracellular calcium leads to increased insulin granules fusion with the cell membrane and increasing the secretion of mature insulin. 

The availability of glipizide is in form of immediate-release tablets of 5 mg, and 10 mg, and extended-release tablets of 2.5 mg, 5 mg, and 10 mg. Glipizide is indicated only for type 2 diabetes. 

The primary adverse effects of sulfonylureas include weight gain and hypoglycemia. The most frequent adverse reactions include diarrhea and nausea. 

Sulfonylureas can cross the placenta and have correlations in some neonatal hypoglycemia cases. Discontinuing this drug is suggested two weeks before expected delivery. 

Reference:

Davies, M.J., Aroda, V.R., Collins, B.S. et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia (2022).https://doi.org/10.1007/s00125-022-05787-2