Association of Patient Profile with Glycemic Control and Hypoglycemia with Insulin Glargine 300 U/mL in Type 2 Diabetes: A Post Hoc Patient-Level Meta-Analysis

ABSTRACT Aims: To examine the association of baseline patient characteristics with study outcomes in people with type 2 diabetes receiving insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100), over a 6-month period. Methods: A post hoc patient-level metaanalysis using data from three multicenter, randomized, open-label, parallel-group, phase 3a studies of similar design, in people previously receiving either basal and prandial insulin, basal insulin ? oral antihyperglycemic drugs, or no prior insulin (EDITION 1, 2 and 3, respectively). The endpoints, glycated hemoglobin (HbA1c), hypoglycemia, body weight change, and insulin dose were investigated by subgroups: age (\65 and C 65 years), body mass index (BMI; \ 30 and C 30 kg/m2), age at onset (\40, 40–50, and [ 50 years), and diabetes duration (\ 10 and C 10 years). Results: Reduction in HbA1c was comparable between insulins, regardless of subgroup. The lower risk of C 1 nocturnal (00:00–05:59 h) confirmed (B 3.9 mmol/L [B 70 mg/dL]) or severe hypoglycemic event with Gla-300 versus Gla-100 was also unaffected by participant characteristics. While heterogeneity of treatment effect between diabetes duration subgroups was seen for the risk of C 1 confirmed (B 3.9 mmol/L [B 70 mg/dL]) or severe hypoglycemic event at any time (24 h), treatment effect consistently favored Gla-300; no evidence of heterogeneity was observed for the other subgroups. Annualized rates of confirmed (B 3.9 mmol/L [B 70 mg/dL]) or severe hypoglycemia and body weight change were not influenced by participant characteristics; a similar pattern was observed with insulin dose. Conclusions: Comparable glycemic control was observed with Gla-300 versus Gla-100, with less hypoglycemia, regardless of age, BMI, age at onset or diabetes duration. Funding: Sanofi. Plain Language Summary: Plain language summary available for this article. Keywords: Glycated Hemoglobin A; Hypoglycemia; Insulin Glargine; Type 2 Diabetes PLAIN LANGUAGE SUMMARY Treatments for patients with type 2 diabetes aim to reduce the levels of blood glucose and can include injections with insulin. However, care must be taken to prevent blood glucose levels falling too low (a state called hypoglycemia). Previous studies have shown that insulin glargine 300 units/mL (Gla-300) provides similar reductions in blood glucose levels as insulin glargine 100 units/mL (Gla-100) but is less likely to cause hypoglycemia. However, different patients may respond differently to treatments depending on their individual clinical and biological characteristics. The aim of this study was to evaluate how different profiles of patients with type 2 diabetes responded to Gla-300 and Gla-100 injections. Patients were grouped by different ages, weights, age at diabetes diagnosis, and number of years since diagnosis of diabetes. We found that Gla-300 and Gla-100 reduced glycated hemoglobin (HbA1c; a marker of blood glucose control over the previous 2–3 months) similarly, regardless of how patients were grouped. However, patients treated with Gla-300 were less likely to experience hypoglycemia than those treated with Gla-100, and this association was also true regardless of different patient characteristics. We therefore concluded that Gla-300 is an effective and safe treatment in patients with type 2 diabetes, regardless of their age, weight, age at diabetes diagnosis, and years since diagnosis

The effect of concomitant DPPIVi use on glycaemic control and hypoglycaemia with insulin glargine 300 U/mL (Gla-300) versus insulin glargine 100 U/mL (Gla-100) in people with type 2 diabetes: A patient-level meta-analysis of EDITION 2 and 3

Abstract Aims To evaluate the effect of concomitant dipeptidyl peptidase IV inhibitor (DPPIVi) use on efficacy and safety of insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100) in people with type 2 diabetes on oral antihyperglycaemic drugs. Methods A post hoc patient-level meta-analysis was performed using data from EDITION 2 (basal insulin [N = 811]) and EDITION 3 (insulin-naïve [N = 878]), multicentre, randomised, openlabel, parallel-group, phase 3a trials of similar design. Endpoints analysed included HbA1c, hypoglycaemia and adverse events, investigated in subgroups of participants with and without concomitant DPPIVi use. Results Of 1689 participants randomised, 107 (13%, Gla-300) and 133 (16%, Gla-100) received DPPIVi therapy. The least squares mean change in HbA1c (baseline to month 6) was comparable between treatment groups, irrespective of DPPIVi use (no evidence of heterogeneity of treatment effect across subgroups, p = 0.753), although group sizes were unbalanced. The cumulative mean number of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemic events, and the risk and annualised rate of such events, were consistently lower for Gla-300 than Gla-100 during the night (between 00:00 and 05:59 h) or at any time of day (24 h period), irrespective of DPPIVi use. Severe hypoglycaemia occurred in 8/838 and 10/844 participants in the Gla-300 and Gla-100 groups, respectively, and was not affected by DPPIVi use. The adverse event profile was similar between treatment groups and DPPIVi subgroups. Conclusions Glycaemic control with Gla-300 was comparable to Gla-100, with less hypoglycaemia during the night and at any time of day (24 h), irrespective of concomitant DPPIVi use

Revealing the last 13,500 years of environmental history from the multiproxy record of a mountain lake (Lago Enol, northern Iberian Peninsula)

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10933-009-9387-7.We present the Holocene sequence from Lago Enol (43°16′N, 4°59′W, 1,070 m a.s.l.), Cantabrian Mountains, northern Spain. A multiproxy analysis provided comprehensive information about regional humidity and temperature changes. The analysis included sedimentological descriptions, physical properties, organic carbon and carbonate content, mineralogy and geochemical composition together with biological proxies including diatom and ostracod assemblages. A detailed pollen study enabled reconstruction of variations in vegetation cover, which were interpreted in the context of climate changes and human impact. Four distinct stages were recognized for the last 13,500 years: (1) a cold and dry episode that includes the Younger Dryas event (13,500–11,600 cal. year BP); (2) a humid and warmer period characterizing the onset of the Holocene (11,600–8,700 cal. year BP); (3) a tendency toward a drier climate during the middle Holocene (8,700–4,650 cal. year BP); and (4) a return to humid conditions following landscape modification by human activity (pastoral activities, deforestation) in the late Holocene (4,650–2,200 cal. year BP). Superimposed on relatively stable landscape conditions (e.g. maintenance of well established forests), the typical environmental variability of the southern European region is observed at this site.The Spanish Inter-Ministry Commission of Science and Technology (CICYT), the Spanish National Parks agency, the European Commission, the Spanish Ministry of Science, and the European Social Fund

Revealing the last 13,500 years of environmental history from the multiproxy record of a mountain lake (Lago Enol, northern Iberian Peninsula)

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10933-009-9387-7.We present the Holocene sequence from Lago Enol (43°16′N, 4°59′W, 1,070 m a.s.l.), Cantabrian Mountains, northern Spain. A multiproxy analysis provided comprehensive information about regional humidity and temperature changes. The analysis included sedimentological descriptions, physical properties, organic carbon and carbonate content, mineralogy and geochemical composition together with biological proxies including diatom and ostracod assemblages. A detailed pollen study enabled reconstruction of variations in vegetation cover, which were interpreted in the context of climate changes and human impact. Four distinct stages were recognized for the last 13,500 years: (1) a cold and dry episode that includes the Younger Dryas event (13,500–11,600 cal. year BP); (2) a humid and warmer period characterizing the onset of the Holocene (11,600–8,700 cal. year BP); (3) a tendency toward a drier climate during the middle Holocene (8,700–4,650 cal. year BP); and (4) a return to humid conditions following landscape modification by human activity (pastoral activities, deforestation) in the late Holocene (4,650–2,200 cal. year BP). Superimposed on relatively stable landscape conditions (e.g. maintenance of well established forests), the typical environmental variability of the southern European region is observed at this site.The Spanish Inter-Ministry Commission of Science and Technology (CICYT), the Spanish National Parks agency, the European Commission, the Spanish Ministry of Science, and the European Social Fund

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Type of concomitant DPPIVi therapy used (pooled randomised population).

<p>Type of concomitant DPPIVi therapy used (pooled randomised population).</p

HbA_1c (mean ± SE) during 6 months of treatment, by visit and DPPIVi use (pooled mITT population).

<p>Data are pooled from EDITION 2 and EDITION 3. CI, confidence interval; DPPIVi, dipeptidyl peptidase IV inhibitor; LS, least squares; mITT, modified intention-to-treat; SE, standard error.</p

Baseline demographic and clinical characteristics, by concomitant DPPIVi use (pooled randomised population).

<p>Baseline demographic and clinical characteristics, by concomitant DPPIVi use (pooled randomised population).</p

Impact of COVID19 pandemic on the incidence of health-care associated Clostridioides difficile infection.

To investigate the impact of COVID19 pandemic on the incidence of health-care associated Clostridioides difficile infection (HA-CDI). Retrospective study conducted in the Hospital Universitario de Valme (HUV) and the Hospital General Universitario de Alicante (HGUA) in Spain between January 2019 and February 2021. The study period was divided into non-COVID19 period (2019 and months from 2020 to 2021 with ≤30 hospitalized COVID19 patients) and COVID19 period (months from 2020 to 2021 with >30 COVID19 patients). HA-CDI incidence rates (IR) were calculated as the number of new CDI cases per 10.000 occupied bed-days (OBD) and antimicrobial consumption by means of the defined daily dose (DDD) per 1000 OBD. During the COVID19 period, HA-CDI IR in the HUV was 2.6 per 10.000 OBD, which was lower than what was observed during the non-COVID19 period (4.1 per 10.000 OBD; p = 0.1). In the HGUA, HA-CDI IR during COVID19 period was 3.9 per 10.000 OBD, which was not significantly different to the IR observed during the non-COVID19 period (3.7 per 10.000 OBD; p = 0.8). There was a slight increase in the total antibiotic consumption during COVID19 period in both hospitals, with significant increases of certain high-risk antibiotics as cephalosporins. HA-CDI incidence has not increased during the COVID19 pandemic in two tertiary centers in Spain, in spite of a slightly higher antibiotic consumption during the COVID19 period in both hospitals. These findings suggest that, in the presence of strict infection control measures, hospital antibiotic consumption might have a lower impact than expected on HA-CDI