Clinical Evidence for the Earlier Initiation of Insulin Therapy in Type 2 Diabetes

Abstract

The natural history of type 2 diabetes mellitus (T2DM) is a relentless progression of b-cell failure and dysregulation of b-cell function with increasing metabolic derangement. Insulin remains the only glucose-lowering therapy that is efficacious throughout this continuum. However, the timing of introduction and the choice of insulin therapy remain contentious because of the heterogeneity of T2DM and the well-recognized behavioral and therapeutic challenges associated with this mode of therapy. Nevertheless, the early initiation of basal insulin has been shown to improve glycemic control and affect long-term outcomes in people with T2DM and is a treatment strategy supported by international guidelines as part of an individualized approach to chronic disease management. The rationale for early initiation of insulin is based on evidence demonstrating multifaceted benefits, including overcoming the glucotoxic effects of hyperglycemia, thereby facilitating ''bcell rest,'' and preserving b-cell mass and function, while also improving insulin sensitivity. Independent of its effects on glycemic control, insulin possesses anti-inflammatory and antioxidant properties that may help protect against endothelial dysfunction and damage resulting in vascular disease. Insulin therapy and the achievement of good glycemic control earlier in T2DM provide long-term protection to end organs via ''metabolic memory'' regardless of subsequent treatments and degree of glycemic control. This is evidenced from long-term observations continuing from trials such as the United Kingdom Prospective Diabetes Study. As such, early initiation of insulin therapy may not only help to avoid the effects of prolonged glycemic burden, but may also positively alter the course of disease progression.

Predictors of HbA1c over 4 years in people with type 2 diabetes starting insulin therapies: The CREDIT study

“…Together, these variables seem to point to an advantage in beginning insulin earlier. Some studies have addressed this point directly, and while the advantages of very early use of insulin over oral agents can be disputed, these studies do not suggest much in the way of detriment either [20,21]. Using the CORE Diabetes Model, Goodall et al [22] using data specific to the UK, suggested that starting insulin rather than continuing oral agents for a further 8 years would increase lifespan by 7.5 months on average, as well as improving quality of life.…”

Intestinal permeation enhancers for oral peptide delivery

“…and low values (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) [165]. The hydrophobic moiety of the surfactant also influences enhancement action.…”

“…improved absorption of heparin following jejunal delivery in rats in vivo [279]. These data are not surprising as the most effective non-ionic surfactants tested in oral peptide delivery have similar hydrocarbon (C 8 -12 ) and ethoxylate ( [8][9][10][11][12][13][14][15][16][17][18][19][20] ) chain length [280]. Not all ethoxylated lipoidal vehicles alter intestinal permeability, for example, Kolliphor® EL (BASF, Germany) [281] and Cremophor® RH60 [282] are poor PEs.…”

Management of Type 2 Diabetes – Methods for Addition of Prandial to Basal Insulin

“…35 Nevertheless, rather than occurring early in treatment progression, initiation and intensification of insulin regimens in practice is often delayed in the face of poor or worsening glycaemic control.…”