Abstract
Dysglycemia results from a deficit in first-phase insulin secretion compounded by increased insulin insensitivity, exposing β cells to chronic hyperglycemia and excessive glycemic variability. Initiation of intensive insulin therapy at diagnosis of type 2 diabetes mellitus (T2DM) to achieve normoglycemia has been shown to reverse glucotoxicity, resulting in recovery of residual β-cell function. The United Kingdom Prospective Diabetes Study (UKPDS) 10-year post-trial follow-up reported reductions in cardiovascular outcomes and all-cause mortality in persons with T2DM who initially received intensive glucose control compared with standard therapy. In the cardiovascular outcome trial, outcome reduction with an initial glargine intervention (ORIGIN), a neutral effect on cardiovascular disease was observed in the population comprising prediabetes and T2DM. Worsening of glycemic control was prevented over the 6.7 year treatment period, with few serious hypoglycemic episodes and only moderate weight gain, with a lesser need for dual or triple oral treatment versus standard care. Several other studies have also highlighted the benefits of early insulin initiation as first-line or add-on therapy to metformin. The decision to introduce basal insulin to metformin must, however be individualized based on a risk–benefit analysis. The landmark ORIGIN trial provides many lessons relating to the concept and application of early insulin therapy for the prevention and safe and effective induction and maintenance of glycemic control in type 2 diabetes. Funding: Sanofi.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-016-0153-3) contains supplementary material, which is available to authorized users.
Highlights
Over the last few decades, there has been a dramatic global increase in the number of people with pre-diabetes [characterized by either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)] and known type 2 diabetes mellitus (T2DM)
In the major CV outcomes trials, United Kingdom Prospective Diabetes Study (UKPDS) [3], Kumamoto [84], PROactive [85], Action to Control Cardiovascular Risk in Diabetes (ACCORD) [5], ADVANCE [7], Veterans Affairs Diabetes Trial (VADT) [4] and STENO-2 [44], the baseline glycemic control was in excess of 7.5%
The outcome reduction with an initial glargine intervention (ORIGIN) trial represents a unique category of patients at an early stage of their disease possessing a high CV risk profile
Summary
Over the last few decades, there has been a dramatic global increase in the number of people with pre-diabetes [characterized by either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)] and known type 2 diabetes mellitus (T2DM). D. Owens (&) Institute of Life Sciences, Swansea University, Swansea, UK e-mail: owensdr@cardiff.ac.uk; owensdr@cf.ac.uk (UKPDS) 10-year post-trial follow-up reported reductions in cardiovascular outcomes and all-cause mortality in persons with T2DM who initially received intensive glucose control compared with standard therapy.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
