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A new meta-analysis finds that eight different diabetes drugs do not improve cardiovascular or all-cause mortality compared with placebo. Researchers from the University of Bari, Italy, and Diaverum, Lund, Sweden, investigated 301 clinical trials that examined the efficacy and safety of glucose-lowering drugs. Nearly 120,000 patients were involved in the trials, all of whom had type 2 diabetes. Overall, 177 trials involved drugs being given as monotherapy; 109 trials of drugs were added to metformin as dual therapy; and 29 trials involved drugs being added to metformin and sulphonylureas as triple therapy. The findings showed that there were no significant differences in the association between the drug classes with cardiovascular, all-cause mortality, serious adverse events, heart attack or stroke. However, the researchers noted "considerable uncertainty about the association of drug treatment with cardiovascular mortality existed within trial evidence, largely because of few events in most available studies." Additionally, there was no data for basal insulin and glucagon-like peptide-1 receptor (GLP-1) agonists as a monotherapy for cardiovascular mortality. The study team's secondary endpoint was HbA1c. They observed that metformin outperformed some of the other drug classes in lowering HbA1c levels, but all other drugs were more effective when added to metformin. The four drug classes that were associated with higher HbA1c levels when compared to metformin were sulphonylureas, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors and α-Glucosidase inhibitors. Meanwhile, sodium-glucose cotransporter-2 (SGLT2) drugs were associated with the lowest risk of hypoglycemia when added to metformin; GLP-1 agonists had the lowest risk when added to both metformin and sulphonylurea; and basal insulin and sulphonylurea were associated with the highest risk of hypoglycemia. "Based on this review, clinicians and patients may prefer to avoid sulphonylureas or basal insulin for patients who wish to minimise hypoglycemia, choose GLP-1 receptor agonists when weight management is a priority, or consider SGLT-2 inhibitors based on their favourable combined safety and efficacy profile," the authors wrote. The findings appear in the Journal of the American Medical Association.
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