Effectiveness and Safety of iGlarLixi (Insulin Glargine 100 U/mL Plus Lixisenatide) in Type 2 Diabetes According to the Timing of Daily Administration: Data from the REALI Pooled Analysis

INTRODUCTION: iGlarLixi (insulin glargine 100 U/mL plus lixisenatide) has demonstrated glycaemic efficacy and safety in adults with inadequately controlled type 2 diabetes mellitus (T2DM). Per the European Medicines Agency's product label, iGlarLixi should be injected once a day within 1 h prior to a meal, preferably the same meal every day when the most convenient meal has been chosen. It is however unknown whether iGlarLixi administration timing affects glycaemic control and safety, as clinical trial evidence is mainly based on pre-breakfast iGlarLixi administration. Therefore, we assessed the effectiveness and safety of iGlarLixi in clinical practice, according to its administration timing. METHODS: Data were pooled from two prospective observational studies including 1303 European participants with T2DM inadequately controlled on oral antidiabetic drugs with or without basal insulin who initiated iGlarLixi therapy for 24 weeks. Participants were classified into four subgroups based on daily timing of iGlarLixi injection: pre-breakfast (N = 436), pre-lunch (N = 262), pre-dinner (N = 399), and those who switched iGlarLixi injection time during the study (N = 206). RESULTS: No meaningful differences in baseline characteristics were observed between the study groups. Least-squares mean reductions in haemoglobin A1c (HbA1c) from baseline to week 24 were substantial in all groups, with the numerically largest decrease observed in the pre-breakfast group (1.57%) compared with the pre-lunch (1.27%), pre-dinner (1.42%), or changed injection time (1.33%) groups. Pre-breakfast iGlarLixi injection also resulted in a numerically greater proportion of participants achieving HbA1c < 7.0% at week 24 (33.7% versus 19.0% for pre-lunch, 25.6% pre-dinner, and 23.2% changed injection time). iGlarLixi was well tolerated across all groups, with low rates of gastrointestinal disorders and hypoglycaemia. Mean body weight decreased similarly in all groups (by 1.3-2.3 kg). CONCLUSION: iGlarLixi was effective and safe regardless of its daily administration time. However, pre-breakfast iGlarLixi injection resulted in a more effective glycaemic control

iGlarLixi (insulin glargine 100 U/ml plus lixisenatide) is effective and well tolerated in people with uncontrolled type 2 diabetes regardless of age: A REALI pooled analysis of prospective real-world data

AIM: To evaluate the effectiveness and safety in routine clinical practice of insulin glargine/lixisenatide (iGlarLixi) in people with type 2 diabetes (T2D) according to age. METHODS: Patient-level data were pooled from 1316 adults with T2D inadequately controlled on oral antidiabetic drugs with or without basal insulin who initiated iGlarLixi for 24 weeks. Participants were classified into age subgroups of younger than 65 years (N = 806) and 65 years or older (N = 510). RESULTS: Compared with participants aged younger than 65 years, those aged 65 years or older had a numerically lower mean body mass index (31.6 vs. 32.6 kg/m2 ), a longer median diabetes duration (11.0 vs. 8.0 years), were more likely to receive prior basal insulin (48.4% vs. 43.5%) and had a lower mean HbA1c (8.93% [74.10 mmol/mol] vs. 9.22% [77.28 mmol/mol]). Similar and clinically relevant reductions in HbA1c and fasting plasma glucose from baseline to week 24 of iGlarLixi therapy were observed regardless of age. At 24 weeks, least-squares adjusted mean (95% confidence interval [CI]) change in HbA1c from baseline was -1.55% (-1.65% to -1.44%) in those aged 65 years or older and -1.42% (-1.50% to -1.33%) in those aged younger than 65 years (95% CI: -0.26% to 0.00%; P = .058 between subgroups). Low incidences of gastrointestinal adverse events and hypoglycaemic episodes were reported in both age subgroups. iGlarLixi decreased mean body weight from baseline to week 24 in both subgroups (-1.6 kg in those aged ≥ 65 years and -2.0 kg in those aged < 65 years). CONCLUSIONS: iGlarLixi is effective and well tolerated in both younger and older people with uncontrolled T2D

The proinsulin-to-adiponectin ratio could be the best practical indicator of the early type 2 diabetes

In 1974, the "Ariadne's thread" (from Greek Mythology, pick one's way through the Labyrinth) of autoimmunity leading to the immunogenetic theory of type 1 diabetes mellitus made it possible to conclude that in this phenotype there exists an unsolved conflict between β-cells and the body's autoreactive immune system. In type 2 diabetes mellitus (T2DM), the "Ariadne's thread" links obesity to pancreatic β-cell biology. Unfortunately, beginning from a wrong interpretation of the relationship between plasma glucose and plasma insulin, the insulin resistance hypothesis was born and claimed as the main defect of T2DM. Overlooking obesity, the understanding of T2DM pathogenesis was delayed by almost half a century. Fortunately, the adipobiology, particularly adipocytes was able to reach the "drawing board" of researchers, and has all the chances these cells to become the "cell of the century", just as the pancreatic β-cell was last the cell of century. The association of diabetes and obesity has motivated us to put pancreatic β-cells and adipocytes head-to-head, that is, we moved from the T2DM-obesity couple to the β-cell-adipocyte couple, appreciating their main secretory products, insulin/proinsulin, C-peptide, amylin (for β-cells), and adiponectin, as well as other numerous adipokines (for adipocytes). We thus propose that the proinsulin-to-adiponectin ratio could become the earliest predictor of dysfunction of these two cell types.Adipobiology 2012; 4: 41-50

Construction and analysis of tag single nucleotide polymorphism maps for six human-mouse orthologous candidate genes in type 1 diabetes.

BACKGROUND: One strategy to help identify susceptibility genes for complex, multifactorial diseases is to map disease loci in a representative animal model of the disorder. The nonobese diabetic (NOD) mouse is a model for human type 1 diabetes. Linkage and congenic strain analyses have identified several NOD mouse Idd (insulin dependent diabetes) loci, which have been mapped to small chromosome intervals, for which the orthologous regions in the human genome can be identified. Here, we have conducted re-sequencing and association analysis of six orthologous genes identified in NOD Idd loci: NRAMP1/SLC11A1 (orthologous to Nramp1/Slc11a1 in Idd5.2), FRAP1 (orthologous to Frap1 in Idd9.2), 4-1BB/CD137/TNFRSF9 (orthologous to 4-1bb/Cd137/Tnrfrsf9 in Idd9.3), CD101/IGSF2 (orthologous to Cd101/Igsf2 in Idd10), B2M (orthologous to B2m in Idd13) and VAV3 (orthologous to Vav3 in Idd18). RESULTS: Re-sequencing of a total of 110 kb of DNA from 32 or 96 type 1 diabetes cases yielded 220 single nucleotide polymorphisms (SNPs). Sixty-five SNPs, including 54 informative tag SNPs, and a microsatellite were selected and genotyped in up to 1,632 type 1 diabetes families and 1,709 cases and 1,829 controls. CONCLUSION: None of the candidate regions showed evidence of association with type 1 diabetes (P values > 0.2), indicating that common variation in these key candidate genes does not play a major role in type 1 diabetes susceptibility in the European ancestry populations studied.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are