The effect of oral antidiabetic agents on A1C levels: a systematic review and meta-analysis

Abstract

Objective: Previous reviews of the effect of oral antidiabetic (OAD) agents on A1C levels summarized studies with varying designs and methodological approaches. Using predetermined methodological criteria, we evaluated the effect of OAD agents on A1C levels.

Research design and methods: The Excerpta Medica (EMBASE), the Medical Literature Analysis and Retrieval System Online (MEDLINE), and the Cochrane Central Register of Controlled Trials databases were searched from 1980 through May 2008. Reference lists from systematic reviews, meta-analyses, and clinical practice guidelines were also reviewed. Two evaluators independently selected and reviewed eligible studies.

Results: A total of 61 trials reporting 103 comparisons met the selection criteria, which included 26,367 study participants, 15,760 randomized to an intervention drug(s), and 10,607 randomized to placebo. Most OAD agents lowered A1C levels by 0.5-1.25%, whereas thiazolidinediones and sulfonylureas lowered A1C levels by approximately 1.0-1.25%. By meta-regression, a 1% higher baseline A1C level predicted a 0.5 (95% CI 0.1-0.9) greater reduction in A1C levels after 6 months of OAD agent therapy. No clear effect of diabetes duration on the change in A1C with therapy was noted.

Conclusions: The benefit of initiating an OAD agent is most apparent within the first 4 to 6 months, with A1C levels unlikely to fall more than 1.5% on average. Pretreated A1C levels have a modest effect on the fall of A1C levels in response to treatment.

Figure 1

Treatment effect by OAD class at 13–18 weeks. Each line represents a treatment effect (●) and 95% CIs (ends of the line). The diamond shape represents a meta-analyzed mean difference for a particular OAD class and dose. *Illustrates the generally accepted maximum daily dose. A, acarbose; Gm, glimepiride; Gp, glipizide; Gy, glyburide; M, miglitol; Me, metformin; Ml, metformin (long-acting); N, nateglinide; P, pioglitazone; R, rosiglitazone; Re, repaglinide; S, sitagliptin; V, vildagliptin.

Figure 2

Treatment effects on A1C by OAD class, dose, and time. Error bars represent 95% CIs. ●, represent pooled, weighted mean differences. ○, represent individual comparison treatment effects. *Treatment effect 1.1 (95% CI 0.8–1.4). †Illustrates the generally accepted maximum daily dose. A, acarbose; AG-α, glucosidase inhibitors; Gm, glimepiride; Gp, glipizide; Gy, glyburide; M, miglitol; Me, metformin; Ml, metformin (long-acting); N, nateglinide; P, pioglitazone; R, rosiglitazone; Re, repaglinide; S, sitagliptin; V, vildagliptin.