Safety concerns for Sulphonylureas- may increase all cause mortality

A recent study found that sulphonylureas have a safety concern when compared to alternate drugs but there may be differences within the drug class. They also found that out of all drugs, glimepiride has the best safety. The study was published in the journal BMC Endocrinology Disorders

There is still discord on the safety of sulfonylurea drugs in the treatment of Type 2 Diabetes. Hence researchers conducted a Systematic review and meta-analysis of randomized controlled trials to compare the all-cause mortality and cardiovascular adverse events of sulfonylureas and drugs with a low risk for hypoglycemia in adults with type 2 diabetes using keywords from databases like MEDLINE (PubMed, OVID), Embase, Cochrane Central Register of Controlled Trials, CINAHL, WOS, and Lilacs. 

The study included randomized controlled head-to-head trials published up to August 2015. They included trials that compared sulfonylureas with active control in adults who are ≥ 18 years old with low hypoglycaemic potential and with type 2 diabetes. Metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists were the drug classes taken in the analysis. All-cause mortality was the primary endpoint. MACE, cardiovascular events, and severe hypoglycemia were the secondary endpoints. 

The eligibility of the study was checked by two reviewers, data were extracted independently, and quality was assessed with any disagreements resolved through discussion. The risk of bias in the included studies was assessed using the Cochrane risk of bias tool for randomized trials v2. Pooled odds ratios (ORs) were estimated by using the fixed effects model. 


  • There were 31 studies in the final analysis with 26,204 patients. out of which 11,711 patients were given sulfonylureas and 14,493 were given comparator drugs.
  • Sulfonylureas had higher odds for all-cause mortality, MACE, myocardial infarction (fatal and non-fatal), and hypoglycemia in comparison to drugs with low hypoglycaemic potential. 
  • Subsequent sensitivity analysis revealed differences in the effect of sulfonylureas, with an increased risk of all-cause mortality with glipizide but not the other molecules.

The present meta-analysis raises concerns about the safety of SUs compared to alternative drugs involved in the current analysis. 

Further reading: Volke V, Katus U, Johannson A, et al. Systematic review and meta-analysis of head-to-head trials comparing sulfonylureas and low hypoglycaemic risk antidiabetic drugs. BMC Endocr Disord. 2022;22(1):251. Published 2022 Oct 19. doi:10.1186/s12902-022-01158-5

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