A multinational team of investigators has conducted a meta-analysis of randomized clinical trials of six months’ duration or longer to determine the relative efficacy and safety of glucose-lowering drugs, including insulin, in patients with type-2 diabetes. The study’s primary outcome was cardiovascular mortality. The investigators found no significant differences between any drug class as monotherapy, dual therapy, or triple therapy.
The new findings were published in the Journal of the American Medical Association.
A total of 301 clinical studies were included in the meta-analysis; 177 trials (56,598 patients) involved diabetes drugs given as monotherapy; 109 trials (53,030 patients) looked at drugs added to metformin (dual therapy); and 29 trials (10,598 patients) investigated drugs added to metformin and sulfonylurea (triple therapy).
Compared with metformin, monotherapy with sulfonylurea, thiazolidinedione , a dipeptidyl peptidase-4 (DPP-4) inhibitor, or an alpha-glucosidase inhibitor was associated with higher hemoglobin A1c (HbA1c) levels. In addition, sulfonylurea and basal insulin were associated with the highest odds of a patient developing hypoglycemia. When added to metformin, diabetes drugs were associated with similar HbA1c levels, whereas sodium-glucose cotransporter-2 (SGLT-2) inhibitors offered the lowest odds of hypoglycemia. When added to metformin and sulfonylurea, glucagon-like peptide-1 (GLP-1) receptor agonists were associated with the lowest odds of hypoglycemia.
None of the studies in the meta-analysis was specifically designed to determine whether any diabetes drugs prolong patients’ lives.
“So what we know is that currently, there is no good evidence that one drug can improve life expectancy better than another—either when they are used as the only drug for treatment, or when added to metformin,” lead researcher Dr. Suetonia Palmer told HealthDay.
The authors concluded that metformin was associated with lower or no significant differences in HbA1c levels compared with any other diabetes drug classes. All of the diabetes 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,” the authors write.
Dr. Kevin Pantalone, a diabetes specialist at the Cleveland Clinic, agrees. “Metformin, in the absence of contraindications or intolerability, should be the first-line agent to treat patients with type 2 diabetes,” he told HealthDay.