Among adults with type 2 diabetes, metformin seems to be superior to sulfonylurea, thiazolidinedione, DPP-4 inhibitor and alpha-glucosidase inhibitor as monotherapy in lowering HbA1c level.
To estimate the relative efficacy and safety associated with glucose-lowering drugs including insulin, a meta-analysis consisting of randomized clinical trials of 24 weeks' or longer duration was carried out «Palmer SC, Mavridis D, Nicolucci A ym. Comparison ...»1. A total of 301 clinical trials (1,417,367 patient-months) were included; 177 trials (56,598 patients) of drugs given as monotherapy; 109 trials (53,030 patients) of drugs added to metformin (dual therapy); and 29 trials (10,598 patients) of drugs added to metformin and sulfonylurea (triple therapy). The primary outcome was cardiovascular mortality. Secondary outcomes included all-cause mortality, serious adverse events, myocardial infarction, stroke, hemoglobin A1c (HbA1C) level, treatment failure (rescue treatment or lack of efficacy), hypoglycemia, and body weight.
There were no significant differences in associations between any drug classes as monotherapy, dual therapy, or triple therapy with odds of cardiovascular or all-cause mortality. Compared with metformin, sulfonylurea (standardized mean difference (SMD), 0.18; 95% CI, 0.01 to 0.34), thiazolidinedione (SMD, 0.16; 95% CI, 0.00 to 0.31), DPP-4 inhibitor (SMD, 0.33; 95% CI, 0.13 to 0.52), and alpha-glucosidase inhibitor (SMD, 0.35; 95% CI, 0.12 to 0.58) monotherapy were associated with higher HbA1C levels. Sulfonylurea (odds ratio (OR), 3.13; 95% CI, 2.39 to 4.12; risk difference (RD), 10%; 95% CI, 7% to 13%) and basal insulin (OR, 17.9; 95% CI, 1.97 to 162; RD, 10%; 95% CI, 0.08% to 20%) were associated with greatest odds of hypoglycemia. When added to metformin, drugs were associated with similar HbA1C levels, while SGLT-2 inhibitors offered the lowest odds of hypoglycemia (OR, 0.12; 95% CI, 0.08 to 0.18; RD, -22%; -27% to -18%). When added to metformin and sulfonylurea, GLP-1 receptor agonists were associated with the lowest odds of hypoglycemia (OR, 0.60; 95% CI, 0.39 to 0.94; RD, -10%; 95% CI, -18% to -2%).