Bari, Italy—Which type 2 diabetes drugs are most effective in preventing cardiovascular disease or prolonging life expectancy?
The answer might not be what you expect. A study published recently in the Journal of the American Medical Association found no significant differences—alone or in combination—in the associations between any of nine available classes of glucose-lowering drugs, including insulin, when it comes to those outcomes.
The meta-analysis of 301 clinical trials involving nearly 120,000 adults with type 2 diabetes was led by researchers from the University of Bari in Italy. Study authors note that, while a large number of glucose-lowering drug classes are approved for type 2 diabetes, randomized clinical trials of diabetes medications have been generally insufficiently powered to establish the role of drug treatment for preventing cardiovascular death.
Of the trials included in the study, 177, including 56,598 patients, were of drugs given as monotherapy; 109 trials, including 53,030 patients, were dual therapy with drugs added to metformin; and 29 trials, including 10,598 patients, were of triple therapy, with drugs added to metformin and sulfonylureas.
Results indicate no significant differences in associations between any drug class as monotherapy, dual therapy, or triple therapy in preventing all-cause mortality, serious adverse events, heart attack, or stroke.
Compared with metformin, sulfonylurea with a standardized mean difference (SMD) of 0.18; thiazolidinedione (SMD, 0.16); DPP-4 inhibitor (SMD, 0.33); and alpha-glucosidase inhibitor (SMD, 0.35) monotherapies were associated with higher HbA1c levels. The greatest risks of hypoglycemia were identified with sulfonylurea with an odds ratio (OR) of 3.13 and basal insulin with an OR of 17.9.
When added to metformin, drugs were associated with similar HbA1c levels, according to the article, which points out that, in that situation, SGLT-2 inhibitors offered the lowest odds of hypoglycemia with an OR of 0.12. In terms of triple therapy, when added to metformin and sulfonylurea, GLP-1 receptor agonists were associated with the lowest odds of hypoglycemia (OR, 0.60).
Study authors caution, however, that considerable uncertainty about the association of drug treatment with cardiovascular mortality existed within trial evidence, largely because of the small number of cardiovascular events in most available studies.
A key finding, on the other hand, is the limited evidence that any glucose-lowering drug stratified by coexisting treatment prolongs life expectancy or prevents cardiovascular disease, according to researchers.
“Metformin was associated with lower or no significant difference in HbA1c levels compared with any other drug classes,” study authors conclude. “All drugs were estimated to be effective when added to metformin. These findings are consistent with American Diabetes Association recommendations for using metformin monotherapy as initial treatment for patients with type 2 diabetes and selection of additional therapies based on patient-specific considerations.”
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