Thiazolidinediones and Sulfonylureas Most Effective in Lowering HbA1C
By Laurie Barclay, MD
Medscape Medical News
June 2, 2010 — Oral antidiabetic drugs (OADs) decrease glycosylated hemoglobin (A1C) levels by approximately 0.5% to 1.25%. The maximal effect is achieved by 3 to 6 months, and thiazolidinediones and sulfonylureas show the greatest efficacy, according to the findings of a systematic review and meta-analysis.
Diana Sherifali, PhD, from the Department of Medicine, McMaster University, Hamilton, Ontario, Canada, and colleagues reported their findings in Diabetes Care, published online ahead of print on May 18.
"Summaries of previous studies of ...OADs suggest that they reduce A1C levels by 0.5-1.5%," the researchers write. "However, this estimated drop in A1C was based on summaries of studies with varying designs, which may lead to over or under estimates of the true effect of OADs."
The current study used predetermined methodologic criteria to determine the effect of OADs on A1C levels more accurately.
Dr. Sherifali and colleagues searched several databases on the medical literature for randomized, placebo-controlled studies published between 1980 and May 2008. A total of 61 trials were selected by 2 independent evaluators. The studies included 26,367 study participants, with approximately 15,000 randomly assigned to treatment and the remainder randomly assigned to placebo.
OAD drug classes included were the alpha glucosidase inhibitors, biguanides, dipeptidyl peptidase-4 inhibitors, meglitinides, sulfonylureas, and thiazolidinediones. Overall, OADs lowered A1C levels by 0.5% 1.25%, whereas thiazolidinediones and sulfonylureas lowered A1C levels, to a slightly greater extent, by approximately 1.0% to 1.25%.
In addition, a higher baseline A1C level was associated with a greater decline in A1C levels with 6 months of OAD treatment; by contrast, the length of disease duration had no effect on response to OADs.
The authors concluded that the benefit of initiating an OAD agent is most apparent within the first 4 to 6 months, with A1C levels unlikely to decrease more than 1.5% on average.
According to the researchers, further carefully conducted OAD trials are needed to account for combinations of OAD drug use and its impact on A1C levels, the effectiveness of long-term OAD use, and the potential for adverse events.
Study Limitations
Independent commentator Philip Home, DM, DPhil, MA, professor of diabetes medicine at Newcastle University, told Medscape Diabetes Endocrinology that limitations of the study were that comparative trials were excluded and that the time course of efficacy is known to be different for sulfonylureas vs other oral medications, which makes comparing efficacy difficult in a study such as this.
"Professionals need to be aware of the limited efficacy of all oral agents, to monitor response early and at frequent intervals, and to add further agents without waiting for their patients to suffer the consequences of continued glucose control above target levels," Dr. Home told Medscape Diabetes Endocrinology.
The study was sponsored by an unrestricted grant from Merck Frosst. Dr. Sherifali has received support through the Heart and Stroke Foundation of Ontario. Coauthor Kara Nerenberg, MD, MSc, has received support through the Canadian Institutes of Health Research. Coauthor Hertzel C. Gerstein, MD, MSc, has received honoraria for providing advice or speaking. These companies include sanofi-aventis, Bristol-Myers Squibb, AstraZeneca, Bayer, GlaxoSmithKline, Lilly, Novo Nordisk, Biovail, Servier, and Roche.
Dr. Home is on the Medscape Diabetes Endocrinology editorial board and has disclosed various financial relationships with AstraZeneca Pharmaceuticals LP; Bristol-Myers Squibb Co; Boehringer-Ingelheim Pharmaceuticals, Inc; GlaxoSmithKline; MannKind Corp; Merck & Co, Inc; Novo Nordisk; Novartis Pharmaceuticals Corp; Roche; sanofi-aventis; Tolerx, Inc; XOMA (US) LLC; and Lilly.
