Glitazones for diabetes prevention found superior to other oral antidiabetic drug classes

Key Points

A systematic review assessing the comparative effectiveness of oral antidiabetic drugs for preventing patients at high risk from progressing to type 2 diabetes has found glitazones (pioglitazone, rosiglitazone), biguanides (metformin), and alpha-glucosidase inhibitors (AGIs) (acarbose, voglibose) reduced the relative risk of diabetes by as much as 63%, whereas insulin secretagogues (sulfonylureas and glinides) had no effect.

Furthermore, glitazones were significantly more efficacious than metformin, the only drug currently recommended by the American Diabetes Association (ADA) guidelines for this purpose.

These results were recently presented at the 70th Scientific Sessions of the ADA in Orlando, Fla.

MORE THERAPY OPTIONS

According to Craig I. Coleman, PharmD, senior investigator on the study and tenured associate professor at the University of Connecticut School of Pharmacy, Storrs, Conn., "Adopting a healthy diet and exercise are the best ways to ward off diabetes, but there are some that may benefit from drug therapy." He continued, "Our research suggests that there may be more drug options out there than previously thought."

Dr Coleman continued, "It's reasonable to believe that any therapy, pharmacologic or nonpharmacologic, that can prevent the occurrence of type 2 diabetes will result in downstream reductions in both morbidity and mortality."

Current ADA guidelines emphasize the use of lifestyle modification to prevent or delay type 2 diabetes. Metformin is the only pharmacologic treatment recommended for diabetes prevention and only for those at very high risk (defined as having both impaired glucose tolerance [IGT] and impaired fasting glucose [IFG] plus 1 additional risk factor such as glycated hemoglobin >6%, hypertension, dyslipidemia, or a first-degree relative with diabetes). These recommendations are based in part on the results of the Diabetes Prevention Project (DPP) study, which suggested that only 14 'high-risk' patients need to be treated with metformin over about 3 years to prevent 1 case of new-onset diabetes.

In order to compare the benefits of using these different antidiabetic classes to prevent the progression of high-risk patients to full-blown diabetes, 2 independent investigators screened citations to identify randomized controlled trials comparing oral antidiabetic agents with either active or nonactive control in adult patients. Data sources included MEDLINE, EMBASE, and Cochrane CENTRAL databases, ranging from the earliest available date of each bibliographic database through February 2010.

The investigators ultimately identified a total of 20 trials evaluating 23,230 patients at high risk for developing type 2 diabetes because they were prediabetic (or obese) for inclusion in the meta-analysis. Upon meta-analysis, investigators found that glitazones, AGIs, and metformin significantly reduced the relative risk of developing diabetes by 64%, 40%, and 27%, respectively, compared with control. This corresponds to number needed to treat (NNT) ranging from 9 to 14. Moreover, glitazones significantly reduced the relative risk of diabetes by 50% compared with metformin and trended toward a 40% risk reduction versus AGIs (RR, 0.60). Sulfonylureas and glinides did not reduce the risk of diabetes, and dipeptidyl peptidase-4 inhibitors lacked any data.

Dr Coleman stressed, "Even though glitazones were found to be most efficacious, other factors including contraindications, adverse events, and other therapeutic benefits outside of diabetes prevention should also be considered when choosing drug therapy for diabetes prevention."

This research was funded by a grant from Takeda Pharmaceuticals North America.

SOURCES

Phung OJ, Sood NA, Sill BE, Coleman CI. Comparative efficacy of oral antidiabetic drugs in preventing type 2 diabetes mellitus [abstract 0658-P]. Presented at: the 70th Scientific Sessions of the American Diabetes Association; June 25–29, 2010; Orlando, Fla. Available at: http://ww2.aievolution.com/ada1001/index.cfm?do=abs.viewAbs&abs=13359. Accessed June 22, 2010.

Knowler WC, Barrett Connor E, Fowler SE, et al; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393–403.

American Diabetes Association. Standards of Medical Care in Diabetes – 2010. Diabetes Care. 2010;33:S11–S61.