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Effects of Initiating Insulin and Metformin on Glycemic Control and Inflammatory Biomarkers Among Patients With Type 2 Diabetes

2009; American Medical Association; Volume: 302; Issue: 11 Linguagem: Inglês

10.1001/jama.2009.1347

1538-3598

Aruna D. Pradhan, Brendan M. Everett, Nancy R. Cook, Nader Rifai, Paul M. Ridker,

Hyperglycemia and glycemic control in critically ill and hospitalized patients

As diabetes is in part an inflammatory condition, the initiation of insulin and/or metformin may beneficially reduce levels of inflammatory biomarkers such as high-sensitivity C-reactive protein (hsCRP).To determine whether insulin alone or combined with metformin lowers levels of hsCRP, IL-6, and soluble tumor necrosis factor receptor 2 (sTNFr2) in patients with recent-onset type 2 diabetes mellitus.Randomized 2 x 2 factorial trial of open-label insulin glargine and placebo-controlled metformin in 500 adults with type 2 diabetes (median time from diagnosis, 2.0 years), suboptimal glycemic control, and elevated hsCRP levels. Patients were recruited from US office-based practices between October 2006 and December 2008.Random allocation to 1 of 4 treatments (placebo metformin only, placebo metformin and insulin glargine, active metformin only, or active metformin and insulin glargine) with dose titration targeting fasting blood glucose less than 110 mg/dL.Change in hsCRP level (primary end point) and change in IL-6 and sTNFr2 levels (secondary end points) from baseline to 14 weeks.Levels of glucose and glycated hemoglobin (HbA(1c)) were significantly reduced with active treatment vs placebo (all P values <.001). Levels of hsCRP were reduced in all 4 groups. There was no significant difference in hsCRP reduction among those allocated to insulin (-11.8%; 95% CI, -18.7% to -4.4%) or to no insulin (-17.5%; 95% CI, -23.9% to -10.5%) (P for difference = .25), or among those allocated to active metformin (-18.1%; 95% CI, -24.4% to -11.1%) or placebo metformin (-11.2%; 95% CI, -18.1% to -3.7%) (P for difference = .17). In the individual treatment groups, despite a differential impact on glucose control, reductions in hsCRP in the metformin (-16.1%; 95% CI, -25.1% to -6.1%) and metformin plus insulin (-20.1%; 95% CI, -28.8% to -10.4%) groups were no different than reductions with placebo alone (-19.0%; 95% CI, -27.8% to -9.1%; P = .67 and .87 vs placebo, respectively). By contrast, hsCRP reduction was attenuated with insulin alone (-2.9%, 95% CI, -13.2% to 8.6%; P = .03 vs placebo). Similar findings were noted for levels of IL-6 and sTNFr2.In patients with recent-onset type 2 diabetes, treatment with insulin or metformin compared with placebo did not reduce inflammatory biomarker levels despite improving glucose control.clinicaltrials.gov Identifier: NCT00366301.