Oral Antidiabetic Drugs and Regression From Prediabetes to Normoglycemia

A Meta-analysis

Olivia J Phung PharmD; William L Baker PharmD BCPS (AQ CV); Vanita Tongbram MBBS MPH; Adarsh Bhardwaj MD; Craig I Coleman PharmD


The Annals of Pharmacotherapy. 2012;46(4):469-476. 

In This Article

Abstract and Introduction


Background: Impaired glucose tolerance, impaired fasting glucose, and elevated hemoglobin A1c are intermediate stages, considered prediabetes, a precursor to overt type 2 diabetes mellitus. Prediabetes is associated with increased risk for cardiovascular disease, independent of diabetes development. Data have shown that various oral antidiabetic drugs can help people regress from prediabetes to normoglycemia.
Objective: To evaluate the efficacy of oral antidiabetic drugs in promoting regression from prediabetes to normoglycemia.
Methods: MEDLINE (1950-November 2011), EMBASE (1990-November 2011), and Cochrane Central Register of Controlled Trials (indexed September 2011) were systematically searched. A manual search of references from reports of clinical trials and review articles was performed to identify additional relevant studies. Randomized controlled trials 12 weeks or more in duration evaluating any of the oral antidiabetic drugs and studying regression from prediabetes to normoglycemia were included. A random-effects model was used to calculate pooled odds ratios with 95% confidence intervals.
Results: Thirteen studies (N = 11,600 participants) were included in the metaanalysis. Use of oral antidiabetic drugs in prediabetic patients was shown to double the odds of achieving normoglycemia compared to controls (OR 2.03, 95% CI 1.54 to 2.67). When individual classes of oral antidiabetic drugs were evaluated, use of thiazolidinediones (OR 2.33, 95% CI 1.93 to 2.81) and α-glucosidase inhibitors (OR 2.02, 95% CI 1.26 to 3.24) was associated with significantly increased odds. However, biguanides (OR 2.04) and sulfonylureas (OR 1.84) failed to reach statistical significance (p = 0.06 and p = 0.39, respectively).
Conclusions: In patients with prediabetes, oral antidiabetic drugs were associated with increased odds of regression to normoglycemia versus placebo/control. Only thiazolidinediones and α-glucosidase inhibitors provided a statistically significant increase in odds of regressing to normoglycemia.


Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), or elevated hemoglobin A1c(A1C) are intermediate stages between normoglycemia and overt type 2 diabetes mellitus (T2DM). These stages are often referred to as prediabetes.[1,2] Criteria for diagnosis of prediabetes are set by the World Health Organization and the American Diabetes Association (ADA)[2–7] and are based on blood glucose levels after oral glucose tolerance test or after fasting or an A1C test. Definitions have changed over the years; for example, the most recent ADA criteria for prediabetes include elevated A1C of 5.7–6.4%, IGT defined by 2-hour plasma glucose level following a 75-g oral glucose tolerance test of 140–199 mg/dL, or IFG defined by fasting plasma glucose level of 100–125 mg/dL.[2] These prediabetic states are associated with increased risk of progression to T2DM[8] and its associated macro- and microvascular complications.[1] Patients with prediabetes are at increased risk of developing cardiovascular disease, independent of diabetes development.[8,9] Moreover, studies have also found that cardiovascular mortality and all-cause mortality are higher in people with prediabetes than in those with normoglycemia.[1]

Active interventions such as lifestyle modification or pharmacologic therapy are attractive options to reduce some of the risks associated with prediabetes. Current guidelines suggest structured lifestyle modification with increased physical activity aimed at losing 5–10% of body weight as the cornerstone of treatment.[2] However, many patients cannot adhere to these measures or need additional assistance to achieve normoglycemia. Data from randomized controlled trials (RCTs) have shown that various oral antidiabetic drugs can help patients regress from prediabetes to normoglycemia.[10–22] The purpose of this meta-analysis is to synthesize the evidence regarding the efficacy of oral antidiabetic drugs in promoting regression from prediabetes to normoglycemia.


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