Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management

Prediabetes (intermediate hyperglycaemia) is a high-risk state for diabetes that is defined by glycaemic variables that are higher than normal, but lower than diabetes thresholds. 5-10% of people per year with prediabetes will progress to diabetes, with the same proportion converting back to normoglycaemia. Prevalence of prediabetes is increasing worldwide and experts have projected that more than 470 million people will have prediabetes by 2030. Prediabetes is associated with the simultaneous presence of insulin resistance and β-cell dysfunction-abnormalities that start before glucose changes are detectable. Observational evidence shows associations between prediabetes and early forms of nephropathy, chronic kidney disease, small fibre neuropathy, diabetic retinopathy, and increased risk of macrovascular disease. Multifactorial risk scores using non-invasive measures and blood-based metabolic traits, in addition to glycaemic values, could optimise estimation of diabetes risk. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention, with evidence of a 40-70% relative-risk reduction. Accumulating data also show potential benefits from pharmacotherapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Regular exercise improves glucose control in diabetes, but the association of different exercise training interventions on glucose control is unclear. To conduct a systematic review and meta-analysis of randomized controlled clinical trials (RCTs) assessing associations of structured exercise training regimens (aerobic, resistance, or both) and physical activity advice with or without dietary cointervention on change in hemoglobin A(1c) (HbA(1c)) in type 2 diabetes patients. MEDLINE, Cochrane-CENTRAL, EMBASE, ClinicalTrials.gov, LILACS, and SPORTDiscus databases were searched from January 1980 through February 2011. RCTs of at least 12 weeks' duration that evaluated the ability of structured exercise training or physical activity advice to lower HbA(1c) levels as compared with a control group in patients with type 2 diabetes. Two independent reviewers extracted data and assessed quality of the included studies. Of 4191 articles retrieved, 47 RCTs (8538 patients) were included. Pooled mean differences in HbA(1c) levels between intervention and control groups were calculated using a random-effects model. Overall, structured exercise training (23 studies) was associated with a decline in HbA(1c) level (-0.67%; 95% confidence interval [CI], -0.84% to -0.49%; I(2), 91.3%) compared with control participants. In addition, structured aerobic exercise (-0.73%; 95% CI, -1.06% to -0.40%; I(2), 92.8%), structured resistance training (-0.57%; 95% CI, -1.14% to -0.01%; I(2), 92.5%), and both combined (-0.51%; 95% CI, -0.79% to -0.23%; I(2), 67.5%) were each associated with declines in HbA(1C) levels compared with control participants. Structured exercise durations of more than 150 minutes per week were associated with HbA(1c) reductions of 0.89%, while structured exercise durations of 150 minutes or less per week were associated with HbA(1C) reductions of 0.36%. Overall, interventions of physical activity advice (24 studies) were associated with lower HbA(1c) levels (-0.43%; 95% CI, -0.59% to -0.28%; I(2), 62.9%) compared with control participants. Combined physical activity advice and dietary advice was associated with decreased HbA(1c) (-0.58%; 95% CI, -0.74% to -0.43%; I(2), 57.5%) as compared with control participants. Physical activity advice alone was not associated with HbA(1c) changes. Structured exercise training that consists of aerobic exercise, resistance training, or both combined is associated with HbA(1c) reduction in patients with type 2 diabetes. Structured exercise training of more than 150 minutes per week is associated with greater HbA(1c) declines than that of 150 minutes or less per week. Physical activity advice is associated with lower HbA(1c), but only when combined with dietary advice.