Evaluation of: Gallwitz B, Rosenstock J, Rauch T et al. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomized, double-blind, non-inferiority trial. Lancet 380(9840), 475-483 (2012). In a recent long-term Phase III comparative trial by Gallwitz et al., the dipeptidyl peptidase-4 inhibitor linagliptin demonstrated noninferior glycemic efficacy compared with glimepiride as add-on therapy to metformin in patients with Type 2 diabetes. Linagliptin was associated with a 54% reduction in the risk of cardiovascular events, mainly driven by a 73% reduction in nonfatal stroke compared with glimepiride. This hypothesis-generating finding may be partly due to the low risk of hypoglycemia inherent to the mechanism of action of linagliptin as well as the relative weight reduction observed with linagliptin compared with glimepiride. The cardiovascular safety profile of linagliptin in direct comparison with glimepiride is being definitively assessed in the CAROLINA trial, due to complete in September 2018 (ClinicalTrials.gov identifier: NCT01243424).
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