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Background: Among people with type 2 diabetes who have severe pancreatic Beta-cell dysfunction, exogenous insulin treatment is essential for controlling glycemia and reducing risks of disease-related complications and mortality. Conventional human insulin preparations are limited by their slow absorption and inability to adequately match the complex basal-bolus pattern of physiologic insulin activity. The development of insulin analogues, including premixed formulations that are designed to mimic physiologic insulin activity, has advanced diabetes management and afforded patients more convenient treatment options. Until recently, however, the benefits and harms of premixed insulin analogues had not been compared with outcomes of other insulin therapies and noninsulin oral antidiabetic agents. In 2008, under the auspices of the Agency for Healthcare Research and Quality (AHRQ), a systematic comparative effectiveness review on this topic was published., Objective: To familiarize health care professionals with the AHRQ comparative effectiveness report on premixed insulin analogues, and to offer and encourage reflections on practical applications of the systematic review findings., Summary: The comparative effectiveness and safety of premixed insulin analogues vary by comparator therapies and outcomes of interest. The AHRQ systematic review indicated that premixed insulin analogues are more effective than long-acting insulin analogues in lowering postprandial glucose and hemoglobin A1c; however, in this comparison the premixed analogues were associated with higher rates of hypoglycemia and more weight gain. Similar effectiveness and safety findings were obtained through the comparison of premixed insulin analogues and noninsulin antidiabetic drugs. Many comparisons did not yield firm conclusions due to a lack of studies or weak evidence.

Background: Evidence comparing premixed insulin analogues (a mixture of rapid-acting and intermediate-acting insulin analogues) with other antidiabetic agents is urgently required to guide appropriate therapy., Purpose: To summarize the English-language literature on the effectiveness and safety of premixed insulin analogues compared with other antidiabetic agents in adults with type 2 diabetes., Data Sources: The authors searched MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to February 2008 and sought unpublished data from the U.S. Food and Drug Administration, European Medicines Agency, and industry., Study Selection: Studies with control groups that compared premixed insulin analogues with another antidiabetic medication in adults with type 2 diabetes., Data Extraction: 2 reviewers using standardized protocols performed serial abstraction., Data Synthesis: Evidence from clinical trials was inconclusive for clinical outcomes, such as mortality. Therefore, the review focused on intermediate outcomes. Premixed insulin analogues were similar to premixed human insulin in decreasing fasting glucose levels, hemoglobin A(1c) levels, and the incidence of hypoglycemia but were more effective in decreasing postprandial glucose levels (mean difference, -1.1 mmol/L; 95% CI, -1.4 to -0.7 mmol/L [-19.2 mg/dL; 95% CI, -25.9 to -12.5 mg/dL]). Compared with long-acting insulin analogues, premixed insulin analogues were superior in decreasing postprandial glucose levels (mean difference, -1.5 mmol/L; CI, -1.9 to -1.2 mmol/L [-27.9 mg/dL; CI, -34.3 to -21.5 mg/dL]) and hemoglobin A(1c) levels (mean difference, -0.39% [CI, -0.50% to -0.28%]) but were inferior in decreasing fasting glucose levels (mean difference, 0.7 mmol/L; CI, 0.3 to 1.0 mmol/L [12.0 mg/dL; CI, 6.0 to 18.1 mg/dL]) and were associated with a higher incidence of hypoglycemia. Compared with noninsulin antidiabetic agents, premixed insulin analogues were more effective in decreasing fasting glucose levels (mean difference, -1.1 mmol/L; CI, -1.7 to -0.6 mmol/L [-20.5 mg/dL; CI, -29.9 to -11.2 mg/dL]), postprandial glucose levels (mean difference, -2.1 mmol/L; CI, -3.4 to -0.8 mmol/L [-37.4 mg/dL; CI, -61.0 to -13.7 mg/dL]), and hemoglobin A(1c) levels (mean difference, -0.49% [CI, -0.86% to -0.12%]) but were associated with a higher incidence of hypoglycemia., Limitations: The literature search was restricted to studies published in English. Data on clinical outcomes were limited. The small number of studies for each comparison limited assessment of between-study heterogeneity., Conclusion: Premixed insulin analogues provide glycemic control similar to that of premixed human insulin and may provide tighter glycemic control than long-acting insulin analogues and noninsulin antidiabetic agents.

Thiazolidinediones, used for the treatment of diabetes mellitus type 2, modulate gene expression by binding to nuclear transcription factor, peroxisome proliferator-activated receptor-gamma. Peroxisome proliferator-activated receptor-gamma is expressed in several tissues, therefore, thiazolidinediones have biological effects on multiple organ systems. Here, we describe evidence that thiazolidinediones have beneficial effects on the cardiovascular system independent of their antidiabetic effect. Studies in animals have clearly shown that thiazolidinediones decrease blood pressure, left ventricular hypertrophy, development of atherosclerotic lesions, and protect myocardium from ischemia/reperfusion injury. Although relatively few studies in humans have been reported, the preponderance of available evidence suggests a beneficial effect of thiazolidinediones. Thus, by modulating gene expression, thiazolidinediones may provide a novel method for the prevention and treatment of cardiovascular diseases., (Copyright 2005 John Wiley & Sons, Ltd.)

In epidemiologic studies, insulin resistance is associated with hypertension. Thiazolidinediones (TZDs) are antidiabetic agents that decrease insulin resistance. Multiple clinical trials have evaluated the effect of TZDs on blood pressure (BP) with inconsistent results. The aim of this study was to estimate the effect of TZDs on BP. The authors searched PubMed for clinical trials published in English. A total of 37 clinical trials that reported a change in BP were included in the analysis. Trials with independent-group design and trials with pre-post design were evaluated separately. When compared with baseline, TZDs lowered systolic BP by 4.70 mm Hg (95% confidence interval, -6.13 to -3.27) and diastolic BP by 3.79 mm Hg (95% confidence interval, -5.82 to -1.77). When compared with placebo, TZDs lowered systolic BP by 3.47 mm Hg (95% confidence interval, -4.91 to -2.02) and diastolic BP by 1.84 mm Hg (95% confidence interval, -3.43 to -0.25). Thus, TZDs lower both systolic and diastolic BP, albeit the BP-lowering effect is small and may not be of clinical significance.