The LANCET Trial: A Randomized Clinical Trial of Lantus for C-reactive Protein Reduction in Early Treatment of Type 2 Diabetes

Study Rationale

Low-grade systemic inflammation as indicated by elevated levels of C-reactive protein (CRP) is often present in patients with type 2 diabetes. Individuals with type 2 diabetes represent a vulnerable population in which cardiovascular event rates are high and among whom CRP reduction may have the greatest impact. While several classes of oral hypoglycemic agents have been shown to lower CRP, data are not available for newer formulations of long-acting insulins such as Lantus (insulin glargine injection) and no study has comprehensively evaluated the relative merit of insulin-providing versus insulin-sensitizing strategies for this purpose.

Investigational Plan

This is a multicenter, community-based, randomized 2x2 factorial trial of Lantus and metformin among patients with type 2 diabetes treated with either diet or oral monotherapy (other than metformin) only who have poor glycemic control and elevated CRP. The primary endpoint is change in CRP. Secondary endpoints include improvement in insulin sensitivity, glycemic control, blood lipids, as well as selected inflammatory and prothrombotic markers, and adipokine levels.

Limited data suggest that short-term insulin administration in patients with poorly controlled type 2 diabetes may lower CRP, but the benefit of CRP reduction that is unique to insulin therapy and independent of glycemic control per se remains uncertain. The insulin-sensitizing agent metformin, a mainstay of anti-diabetic therapy, has been shown to reduce macrovascular complications among patients with type 2 diabetes and, in some but not all randomized clinical trials, also has a modest CRP-lowering effect. This study is designed to assess whether the use of Lantus either alone or in combination with metformin lowers CRP over a 14-week treatment period.