Effects of initiating insulin and metformin on glycemic control and inflammatory biomarkers among patients with type 2 diabetes: the LANCET randomized trial.

Full Abstract

CONTEXT: 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). OBJECTIVE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTION: 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. MAIN OUTCOME MEASURES: Change in hsCRP level (primary end point) and change in IL-6 and sTNFr2 levels (secondary end points) from baseline to 14 weeks. RESULTS: 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. CONCLUSION: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00366301.

Author information

Author/s: Pradhan, Aruna D (AD); Everett, Brendan M (BM); Cook, Nancy R (NR); Rifai, Nader (N); Ridker, Paul M (PM);

Affiliation: Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital and Harvard Medical School, 900 Commonwealth Ave E, Boston, MA 02215-1204, USA. apradhan(-atsign-)partners.org

Journal and publication information

Publication Type: Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

Journal: JAMA : the journal of the American Medical Association (JAMA), published in United States. (Language: eng)

Reference: 2009-Sep; vol 302 (issue 11) : pp 1186-94

Dates: Created 2009/09/16; Completed 2009/09/22;

PMID: 19755697, status: MEDLINE (last retrieval date: 9/22/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Biological Markers - blood
Blood Glucose
C-Reactive Protein - metabolism
Diabetes Mellitus, Type 2 - blood; drug therapy
Drug Therapy, Combination
Female
Hemoglobin A, Glycosylated - analogs & derivatives; metabolism
Humans

Humans
Hypoglycemic Agents - administration & dosage; therapeutic use
Insulin - administration & dosage; analogs & derivatives; therapeutic use
Interleukin-6 - blood
Male
Metformin - administration & dosage; therapeutic use
Middle Aged
Receptors, Tumor Necrosis Factor, Type II - blood

Associated Chemicals: Biological Markers (0) ; Blood Glucose (0) ; Hemoglobin A, Glycosylated (0) ; Hypoglycemic Agents (0) ; Interleukin-6 (0) ; Receptors, Tumor Necrosis Factor, Type II (0) ; glargine (0) ; glucosylated hemoglobin A (0) ; Insulin (11061-68-0) ; Metformin (657-24-9) ; C-Reactive Protein (9007-41-4)

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