Oral Antidiabetic Drugs and Regression from Prediabetes to Normoglycemia: A Meta-Analysis

Abstract

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Background:

Impaired glucose tolerance, impaired fasting glucose, and elevated hemoglobin A_1c 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.

Keywords

hypoglycemic drugs meta-analysis normoglycemia oral antidiabetic drugs prediabetes

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References

The DECODE study group. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. Lancet 1999; 354:617–21.

American Diabetes Association. Standards of medical care in diabetes–2011. Diabetes Care 2011; 34:S11–S51.

World Health Organization. Diabetes mellitus. World Health Organ Tech Rep Ser no. 727, 1985.

World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications. Report of a WHO consultation. Part 1: Diagnosis and classification of diabetes mellitus. Geneva: World Health Organization, 1999.

American Diabetes Association. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997; 20:1183–97.

The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1999; 22(suppl I):S5–S19.

The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 2003; 26:3160–7.

Ramachandran

, Snehalatha

, Dharmaraj

, Viswanathan

. Prevalence of glucose intolerance in Asian Indians. Urban-rural difference and significance of upper body adiposity. Diabetes Care 1992; 15:1348–55.

Harris

. Impaired glucose tolerance in the US population. Diabetes Care 1989; 12:464–74.

10.

DeFronzo

, Tripathy

, Schwenke

. Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med 2011; 364:1104–15.

11.

Kawamori

, Tajima

, Iwamoto

, Kashiwagi

, Shimamoto

, Kaku

. Voglibose for prevention of type 2 diabetes mellitus: a randomised, double-blind trial in Japanese individuals with impaired glucose tolerance. Lancet 2009; 373:1607–14.

12.

The DREAM Trial Investigators. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 2006; 368:1096–105.

13.

Eriksson

, Lehtovirta

, Ehrnström

, Salmela

, Groop

. Long-term beneficial effects of glipizide treatment on glucose tolerance in subjects with impaired glucose tolerance. J Int Med 2006; 259:553–60.

14.

Hung

, Hsieh

, Pei

. Rosiglitazone improves insulin sensitivity and glucose tolerance in subjects with impaired glucose tolerance. Clin Endocrinol 2005; 62:85–91.

15.

Bennett

, Agrawal

, Elasha

. Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance. Diabet Med 2004; 21:415–22.

16.

Fang

, Li

, Chen

. Effect of medicine and non-medicine intervention on the outcomes of patients with impaired glucose tolerance: 5-year follow-up. Chin J for Clin Rehab 2004; 8:6562–3.

17.

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.

18.

Chiasson

, Josse

, Gomis

, Hanefeld

, Karasik

, Laakso

. Acabose for the prevention of type 2 diabetes mellitus: the STOP-NIDDM randomized trial. Lancet 2002; 359:2072–7.

19.

Lehtovirta

, Forsen

, Gullstrom

. Metabolic effects of metformin in patients with impaired glucose tolerance. Diabet Med 2001; 18:578–83.

20.

, Pan

, Li

. Effect of metformin on patients with impaired glucose tolerance. Diabet Med 2001; 16:477–81.

21.

Wang

, Xu

, Wang

. An evaluation on efficacy of acarbose interfering treatment on IGT. Shanxi Clin Med J 2000; 9:116–7.

22.

Antonucci

, McLain

, Whitcomb

, Lockwood

. Impaired glucose tolerance is normalized by treatment with the thiazolidinedione troglitazone. Diabetes Care 1997; 20:188–93.

23.

Higgins

JPT

, Green

. Cochrane handbook for systematic reviews of interventions, Version 5.0.0 (updated February 2008). The Cochrane Collaboration, 2008. www.cochrane-handbook.org (accessed 2010 Nov 5).

24.

Wong

SSL

, Wilczynski

, Haynes

. Comparison of top-performing search strategies for detecting clinically sound treatment studies and systematic reviews in MEDLINE and EMBASE. J Med Libr Assoc 2006; 94:451–5.

25.

Jadad

, Moore

, Carroll

. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996; 17:1–12.

26.

DerSimonian

, Laird

. Meta-analysis in clinical trials. Control Clin Trials 1986; 7:177–88.

27.

The DECODE study group, the European Diabetes Epidemiology Group. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med 2001; 161:397–405.

28.

Package insert. Actos (pioglitazone). Deerfield, IL: Takeda Pharmaceuticals America Inc., September 2009.

29.

Package insert. Avandia (rosiglitazone). Research Triangle Park, NC: GlaxoSmithKline, October 2008.

30.

Nissen

, Wolski

. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007; 356:2457–71.

31.

Singh

, Loke

, Furberg

. Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA 2007; 298:1189–95.

32.

Package insert. Precose (acarbose). Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc., August 2008.

33.

Package insert. Glyset (miglitol). Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc., September 2009.

34.

Nathan

. Initial management of glycemia in type 2 diabetes mellitus. N Engl J Med 2002; 347:1342–9.

35.

Package insert. Glucophage (metformin). Princeton, NJ: Bristol-Myers Squibb Co., January 2009.

36.

Package insert. Amaryl (glimepiride). Bridgewater, NJ: sanofi–aventis, May 2009.

37.

Package insert. Glucotrol (glipizide). New York, NY: Pfizer Inc., September 2006.

38.

Package insert. Micronase (glyburide). New York, NY: Pfizer Inc., January 2009.