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Comparing Medications for Adults With Type 2 Diabetes

Slide: 15 of 35

Intermediate Outcomes: Overview of HbA1c Results

Hemoglobin A1c (HbA1c). Most diabetes medications (metformin, thiazolidinediones, sulfonylureas, and repaglinide) reduced HbA1c to a similar degree by about 1 absolute percentage point when compared with baseline values. Two-Drug combination therapies with metformin generally were more effective at reducing HbA1c compared with metformin monotherapy by about 1 absolute percentage point. However, metformin lowered HbA1c approximately 0.4% better than did the DPP-4 inhibitors. Most combinations of metformin, sulfonylureas, and thiazolidinediones had similar efficacies in lowering HbA1c. These results were consistent with the 2007 systematic review, except for the data on the DPP-4 inhibitors that was lacking at that time because they were not yet Food and Drug Administration (FDA)-approved. Although comparisons with the GLP-1 receptor agonists were included, evidence for these comparisons was graded as insufficient or low, limiting conclusions. Although firm conclusions could not be drawn on the comparative effectiveness of two-drug combinations due to few head to head studies, most combination therapies showed similar reductions in HbA1c.

The two long-term studies excluded from the meta-analysis (ADOPT and UKPDS) lasting longer than 4 years have conflicting results related to glycemic control. ADOPT favored metformin over sulfonylurea after a median followup of 4 years. UKPDS appeared to favor sulfonylurea over metformin in overweight individuals on monotherapy after 9 years of followup, while showing no between-group differences in mean HbA1c after 10 years of followup for those subjects where other diabetes medications were added to their monotherapy regimen. One of the UKPDS studies was included in this report since the article evaluated only those overweight individuals assigned metformin or sulfonylurea who did not have a second medication added over time. The rest of the UKPDS studies were excluded from this section of the report since they were allowed to add other diabetes medications to their initial monotherapy groups, making it impossible to discern comparative drug effects.