Diabetes Consensus Paper Advises Limited Use of Sulfonylureas

Miriam E. Tucker

June 11, 2020

A European consensus statement advises limiting routine use of sulfonylureas for the treatment of type 2 diabetes to "settings that are resource-constrained and in the short term."

The writing project, organized by medical communications agency Edra and supported by AstraZeneca, was published online June 1 in Diabetes Obesity and Metabolism.

The authors point to current guidelines to "govern the general approach to diabetes management" and offer this new consensus paper as supplemental guidance specifically on the use of sulfonylureas as second-line treatment (after metformin) in type 2 diabetes.

The statement was prompted by "the large differences among guidelines from different countries in sulfonylurea positioning in type 2 diabetes treatment algorithms," say lead author Agostino Consoli, MD, professor of endocrinology at the D'Annunzio University of Chieti-Pescara, Chieti, Italy, and colleagues,

"Guidelines and approaches are changing rapidly and most agree that preference should be given to agents whose benefits extend beyond glucose-lowering," say Consoli and coauthors, who are from several other European countries as well as Israel and Canada.

"Notwithstanding, sulfonylureas and metformin remain the most widely prescribed antihyperglycemic agents worldwide."

Three Basic Recommendations; Gliclazide Is Preferred Sulfonylurea  

The article summarizes evidence supporting use of newer classes of glucose-lowering agents and discusses the hypoglycemia and weight gain risks associated with sulfonylureas. It then provides three basic recommendations in the conclusion section, as follows.

(1) Because the main goal of type 2 diabetes treatment is to reduce cardiorenal endpoints and prolong survival, newer diabetes medications including sodium-glucose cotransporter type 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists and, to a lesser extent, dipeptidyl peptidase-4 (DPP-4) inhibitors are preferred over sulfonylureas as second-line treatment after metformin. This is based on the following evidence:

  • The minimal hypoglycemic risk associated with their use.

  • Their positive (GLP-1 agonists, SGLT2 inhibitors) or neutral (DPP-4 inhibitors) cardiovascular effects.

  • Their positive renal effects (SGLT2 inhibitors >> GLP-1 agonists > DPP-4 inhibitors).

  • Their neutral (DPP-4 inhibitors) or positive (GLP-1 agonists, SGLT2 inhibitors) effects on body weight.

  • Their possible longer glycemic durability.

  • Their ease of use, mostly without titration or need for self-blood glucose monitoring.

(2) Although newer diabetes medications may be preferred in all patients with type 2 diabetes for whom they're not contraindicated, SGLT2 inhibitors and/or GLP-1 agonists are particularly strongly recommended for people with established cardiovascular disease or at very high risk, in the absence of contraindications. (No study has shown a cardiovascular or renal benefit for sulfonylureas.)

(3) Routine use of sulfonylureas as second-line agents might be acceptable in settings that are resource-constrained and in the short term. When they are prescribed, the following should be considered:

  • Gliclazide may be the preferred agent (due to its relatively lower hypoglycemia risk).

  • Patients should be educated about hypoglycemia.

  • Use of self-monitoring of blood glucose should be considered to minimize hypoglycemic side effects.

  • "Given the accrued evidence of the positive impact of SGLT2 inhibitors and GLP-1 agonists on vascular, cardiac, and renal endpoints, use of sulfonylureas instead of SGLT2 inhibitors and GLP-1 agonists needs a strong and well-supported motivation, since it may deprive the patient of possibly important cardiorenal protective effects," the panel concludes.

The project was sponsored by Edra, a medical communications agency, with unconditional funding provided by AstraZeneca. Consoli has reported consulting relationships with AstraZeneca and Novo Nordisk; participating in advisory panels for Abbot, AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Mundipharma, Novo Nordisk, Sanofi Aventis, and Takeda; receiving speaker fees from Abbott, AstraZeneca, Boehringer Ingelheim, Bruno Farmaceutici, Eli Lilly, MSD, Mundipharma, Novo Nordisk, Sanofi Aventis, and Takeda; and receiving research support from AstraZeneca, Eli Lilly, and Novo Nordisk.

Diabetes Obes Metab. Published online June 1, 2020. Full text

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