Comparing a daily versus weekly titration algorithm in people with type 2 diabetes switching from basal insulin to iGlarLixi in the LixiLan ONE CAN randomized trial.

AIM: To compare the efficacy and safety of a simple daily titration algorithm compared with a weekly dose adjustment of iGlarLixi in people with type 2 diabetes. MATERIALS AND METHODS: LixiLan ONE CAN (NCT03767543), a randomized, 26-week, open-label, multicentre phase 3 trial conducted in Canada, involved 265 people with type 2 diabetes and an HbA1c of ≥7.5% to ≤ 10.5% or less (≥58 to ≤91 mmol/mol) on basal insulin for 6 months or longer. Participants were randomized 1:1 with instructions to self-titrate iGlarLixi daily (1 unit/day) or once weekly (2 or 4 units/week) to a common target fasting plasma glucose of 4.4 to 5.6 mmol/L (79 to 101 mg/dl). The primary objective was to show non-inferiority of the daily versus weekly titration algorithm. RESULTS: At 26 weeks, daily titration of iGlarLixi was not inferior to a weekly titration for both the prespecified primary endpoint of change in HbA1c from baseline (least square [LS] mean change: -1.24% vs. -0.92%, respectively; LS mean difference: 0.32%; 95% CI [0.07, 0.57]; P < .0001) and for the secondary endpoint of change in weight from baseline (LS mean change: -0.22 vs. +0.81 kg, respectively; LS mean difference: 1.03 kg; 95% CI [0.01, 2.06]; P < .0001). Indeed, for both the primary and secondary outcome, the daily titration of iGlarLixi was superior. There were no statistically significant differences in hypoglycaemia incidence between the two titration strategies during the 26-week study. CONCLUSION: A daily titration algorithm for switching basal insulin to iGlarLixi was shown to be non-inferior and superior for glycaemic control and weight compared with weekly titration.

Persistence of GLP-1 RA in combination with basal insulin among adults with type 2 diabetes in Canada.

AIMS: The purpose of this study is to assess the persistence of Canadians with Type 2 diabetes mellitus (T2D) on loose-dose combination treatment (i.e., administered by separate devices) with a glucagon-like peptide 1 receptor agonist (GLP-1 RA) and basal insulin over 12 months. METHODS: This study is a retrospective cohort study of T2D adults using a Canadian longitudinal prescription database over a 5-year period. Cohort 1 (n = 12,411) is a primary cohort including only individuals inexperienced with the combination therapy at index. Cohort 2 (n = 13,498) is an exploratory cohort and includes everyone regardless of previous experience on the loose-dose combination therapy. The primary endpoint is the proportion of individuals persistent and average days persistent to the loose-dose combination therapy at 12 months in Canada. RESULTS: In Cohort 1, overall persistence was 47% in the 12-month period post-index. Persistence is similar when including all inexperienced and subsequent loose-dose combination experiences in Cohort 2 (45%). CONCLUSIONS: Canadian T2D adults taking a loose-dose combination therapy of a GLP-1 RA and basal insulin had overall low persistence and lower than reports from previous studies of GLP-1 RA or basal insulin alone. Improving persistence to combination therapy with GLP-1 RA plus basal insulin is an important issue to explore in clinical practice.

Osteoarthritis, mobility-related comorbidities and mortality: an overview of meta-analyses.

AIMS: The objective of this review was to examine the relationship between osteoarthritis (OA) and mobility-related comorbidities, specifically diabetes mellitus (DM) and cardiovascular disease (CVD). It also investigated the relationship between OA and mortality. METHODS: An overview of meta-analyses was conducted by performing two targeted searches from inception to June 2020. The association between OA and (i) DM or CVD (via PubMed and Embase); and (ii) mortality (via PubMed) was investigated. Meta-analyses were selected if they included studies that examined adults with OA at any site and reported associations between OA and DM, CVD, or mortality. Evidence was synthesized qualitatively. RESULTS: Six meta-analyses met inclusion criteria. One meta-analysis of 20 studies demonstrated a statistically significant association between OA and DM, with pooled odds ratio of 1.41 (95% confidence interval: 1.21, 1.65; n = 1,040,175 patients). One meta-analysis of 15 studies demonstrated significantly increased risk of CVD among OA patients, with a pooled risk ratio of 1.24 (1.12, 1.37, n = 358,944 patients). Stratified by type of CVD, OA was shown to be associated with increased heart failure (HF) and ischemic heart disease (IHD) and reduced transient ischemic attack (TIA). There was no association reported for stroke or myocardial infarction (MI). Three meta-analyses did not find a significant association between OA (any site) and all-cause mortality. However, OA was found to be significantly associated with cardiovascular-related death across two meta-analyses. CONCLUSION: The identified meta-analyses reported significantly increased risk of both DM and CVD (particularly, HF and IHD) among OA patients. It was not possible to confirm consistent directional or causal relationships. OA was found to be associated with increased mortality, but mostly in relation to CVD-related mortality, suggesting that further study is warranted in this area.