Initiation of insulin glargine therapy in type 2 diabetes subjects suboptimally controlled on oral antidiabetic agents: results from the AT.LANTUS trial*

Abstract

Running title: Glargine initiation in insulin-naïve type 2 diabetes AT.LANTUS: A Trial comparing LANTUS Algorithms to achieve Normal blood glucose Targets in subjects with Uncontrolled blood Sugar 2 ABSTRACT Objective: For many patients with type 2 diabetes, oral antidiabetic agents (OADs) do not provide optimal glycemic control, necessitating insulin therapy. Fear of hypoglycemia is a major barrier to initiating insulin therapy. The AT.LANTUS study investigated optimal methods to initiate and maintain insulin glargine (LANTUS ® ; glargine) therapy using two treatment algorithms. This sub-group analysis investigated the initiation of once-daily glargine therapy in patients sub-optimally controlled on multiple OADs. Research design and methods:This was a 24-week, multinational (59 countries), multicenter (611), randomized study. Algorithm 1 was a clinic-driven titration and Algorithm 2 was a patient-driven titration. Titration was based on target fasting blood glucose ≤100 mg/dL (≤5.5 mmol/L). Algorithms were compared for incidence of severe hypoglycemia (requiring assistance and blood glucose <50 mg/dL [<2.8 mmol/L]) and baseline-to-endpoint change in HbA 1c . Results:Of the 4961 patients enrolled in the study, 865 were included in this sub-group analysis: 340 received glargine plus 1 OAD; 525 received glargine plus >1 OAD. Incidence of severe hypoglycemia was <1%. HbA 1c decreased significantly between baseline and endpoint for patients receiving glargine plus 1 OAD (-1.4%, p<0.001; Algorithm 1 -1.3% vs Algorithm 2 -1.5%; p=0.03) and glargine plus >1 OAD (-1.7%, p<0.001; Algorithm 1 -1.5%vs Algorithm 2 -1.8%; p=0.001). Conclusions:This study shows that initiation of once-daily glargine with OADs results in significant reduction of HbA 1c with a low risk of hypoglycemia. The greater reduction in HbA 1c was seen in patients randomized to the patient-driven algorithm (Algorithm 2) on one or more than one OAD. Following diagnosis, patients are generally advised to make a number of lifestyle changes, focussed on increasing physical activity levels [7] and diet [8]. However, such programs are usually insufficient by this stage of the diabetes [9]. The progressive nature of T2DM, characterized by a decline in β-cell function [10,11] and deterioration in glycemic control [12], means that pharmacologic interventions are usually required [13]. Oral antidiabetic agents (OADs), for example, sulfonylureas, metformin and glitazones are therapeutic interventions used in monotherapy or in combination. However, to achieve and maintain good glycemic control, OADs, even in combination, are insufficient [14] and insulin therapy is often required [13].Both patients and physicians may be reluctant to start insulin therapy [6,15,16]. The fear of hypoglycemia, needle anxiety and weight gain are among the reasons cited that actively discourage insulin therapy. Therefore, it is important that for insulin therapy to be effective in patients with type 2 diabetes, these barriers must be overcome.Insulin glargine (LANTUS ® , glargine) is...

Efficacy of switching from premixed insulin to insulin glargine regimen in Type 2 diabetes mellitus patients with different islet functions

“…Previous studies (10)(11)(12)(13)(14) have demonstrated improved glycaemic control after premixed insulin/insulin analogue Table II. Comparison of main efficacy indices prior to and after switch in the selected patients (± standard deviation).…”

“…Several studies have investigated such novel treatment strategies (10)(11)(12)(13)(14) by adopting a two-back-one strategy, where premixed insulin/insulin analogues that were ineffective in patients with T2DM were replaced with insulin glargine plus OADs. Improved glycaemic control was observed in the patients following the switch in regimen.…”

Self-regulation theory and self-monitoring of blood glucose behavior in type 2 diabetes mellitus.

“…If an individual perceives their illness to be easily understood, they may be more likely to adapt their behaviors based on their own knowledge of the illness. One study identified that in their sample of individuals newly diagnosed with T2DM, 33% admitted that they did not understand diabetes and 73% were unclear about which symptoms might relate to diabetes or other health concerns (Davies, Lavalle-Gonzalez, Storms, & Gomis, 2008). If an illness is seen as confusing, the individual may feel apprehensive in instances requiring decision-making and experience affective distress or low self-efficacy.…”

“…Research has supported the IPQ-R as having acceptable to excellent reliability 2011), and it has been used to measure change in illness perceptions in previous diabetes research trials (Davies et al, 2008;Skinner et al, 2011).…”

“…Specific items relate to feelings, perceptions and mood related to their general care regimen and living with diabetes. It is proposed that the construct measured by the sum of these responses is overall "emotional functioning" specific to diabetes (Polonsky et al, 1995), or level of diabetes distress, and has been used in medical research trials as a quality of life outcome (Davies et al, 2008). It continues to be the most frequently used, and recommended, measure of diabetes distress in the literature (Beverly, 2014).…”