MARGINALISATION OF YAK HERDERS IN BHUTAN: CAN PUBLIC POLICY GENERATE NEW STABILITIES THAT CAN SUPPORT THE TRANSFORMATION OF THEIR SKILLS AND ORGANISATIONS? AND BONDS TO TERRITORIES: A CASE STUDY IN FRANCE AND BRAZIL

N° ISBN - 978-2-7380-1284-5International audienceBhutan is a small Himalayan Monarchy populated with 672,425 inhabitants and located between the subtropical Indian plains and the Tibetan plateau. The yak herders (less than 5% of the population) occupy the Northern belt of the country, alpine region ranging between 2,500 and 6,000m. Yaks ensure their livelihoods with the provision of manure, draught power, meat, hair and dairy products and the possibility to barter the surplus with grains, salt, tools or clothes. Until the 50's Bhutan was still a feudal state isolated from the rest of the world. An original approach to development was put in place to modernise the economy, prioritizing the growth national happiness over Growth Domestic Product. This communication questions the capacity of this development strategy to prevent the marginalisation of yak herding taking place elsewhere in the world. It highlights the footing of the traditional yak farming systems, presents the driving forces of modernisation and analyses as a transfer of complexity the resulting pressures on the yak herding resources and social linkages. It appears that the Bhutanese middle path for development may have prolonged the existence of the yak farming system. Yet it failed so far to create a stable environment able to support the transformation of the herders' skills and organisations and to stabilise their income. Just as it benefited some mountainous areas in Europe, it seems worth investigating the opportunity to add value and to restore the image of the herding activity through a work on the quality of the yak products

Impact of Age on the Effectiveness and Safety of Insulin Glargine 300 U/mL: Results from the REALI European Pooled Data Analysis

Introduction: Patients aged ≥ 65 years continue to be underrepresented in clinical studies related to type 2 diabetes mellitus (T2DM). Accordingly, the REALI pooled analysis was performed to evaluate the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) across different age subgroups, using data from 14 interventional and non-interventional studies. Methods: Pooled efficacy and safety data were collected from 8106 European patients with uncontrolled T2DM who were initiated on or switched to Gla-300 injected once daily for 24 weeks. Patients were categorised into five age subgroups: < 50 (N = 727), 50–59 (N = 2030), 60–69 (N = 3054), 70–79 (N = 1847) and ≥ 80 years (N = 448). Results: Mean baseline haemoglobin A1c (HbA1c) decreased linearly from the youngest (9.10%) to the oldest (8.46%) age subgroup. Following Gla-300 initiation, there were similar HbA1c reductions across age groups, with a least squares mean (95% confidence interval) change in HbA1c from baseline to week 24 of − 1.09% (− 1.18 to − 1.00), − 1.08% (− 1.14 to − 1.03), − 1.12% (− 1.17 to − 1.07), − 1.18% (− 1.24 to − 1.12) and − 1.11% (− 1.23 to − 0.99) in the < 50, 50–59, 60–69, 70–79 and ≥ 80 years subgroups, respectively. The incidences and event rates of reported hypoglycaemia were overall low. Compared to younger age subgroups, lower incidences of symptomatic hypoglycaemia occurring at any time of the day (5.9 vs. 7.6–9.4% for the younger subgroups) or during the night (0.5 vs. 1.6–2.5%) were recorded in patients aged ≥ 80 years. By contrast, the highest incidence of severe hypoglycaemia occurring any time of the day was reported in the subgroup aged ≥ 80 years (1.1 vs. 0.1–0.6% for the younger age subgroups). Conclusion: Gla-300 initiated in patients with uncontrolled T2DM provides glycaemic improvement with a favourable safety profile across a wide range of ages

Rationale and methodology for a European pooled analysis of postmarketing interventional and observational studies of insulin glargine 300 U/mL in diabetes: Protocol of REALI project

Introduction Type 2 diabetes mellitus (T2DM) is a common and heterogeneous disease. Using advanced analytic approaches to explore real-world data may identify different disease characteristics, responses to treatment and progression patterns. Insulin glargine 300 units/mL (Gla-300) is a second-generation basal insulin analogue with preserved glucose-lowering efficacy but reduced risk of hypoglycaemia. The purpose of the REALI pooled analysis described in this paper is to advance the understanding of the effectiveness and real-world safety of Gla-300 based on a large European patient database of postmarketing interventional and observational studies. Methods and analysis In the current round of pooling, REALI will include data from up to 10 000 subjects with diabetes mellitus (mostly T2DM) from 20 European countries. Outcomes of interest include change from baseline to week 24 in haemoglobin A 1c, fasting plasma glucose, self-measured plasma glucose, body weight, insulin dose, incidence and rate of any-time-of-the-day and nocturnal hypoglycaemia. The data pool is being investigated using two complementary methodologies: a conventional descriptive, univariate and multivariable prognostic analysis; and a data-mining approach using subgroup discovery to identify phenotypic clusters of patients who are highly associated with the outcome of interest. By mid-2019, deidentified data of 7584 patients were included in the REALI database, with a further expected increase in patient number in 2020 as a result of pooling additional studies. Ethics and dissemination The proposed study does not involve collection of primary data. Moreover, all individual study protocols were approved by independent local ethics committees, and all study participants provided written informed consent. Furthermore, patient data is deidentified before inclusion in the REALI database. Hence, there is no requirement for ethical approval. Results will be disseminated via peer-reviewed publications and presentations at international congresses as data are analysed

Does Gender Influence the Effectiveness and Safety of Insulin Glargine 300 U/ml in Patients with Uncontrolled Type 2 Diabetes? Results from the REALI European Pooled Analysis

Introduction: Gender differences in risk factors and treatment outcomes for type 2 diabetes mellitus (T2DM) may exist. We used the REALI European database to investigate whether there were gender-specific differences in baseline characteristics and clinical outcomes among patients with inadequately controlled T2DM initiated on insulin glargine 300 U/ml (Gla-300). // Methods: Data were pooled from 14 multicentre, prospective, interventional and non-interventional studies. Impact of gender on glycaemic control, insulin dose, body weight and hypoglycaemia was evaluated after 12 and 24 weeks of Gla-300 treatment. // Results: Women (N = 3857) were older than men (N = 4376) (median age, 65.0 versus 63.0 years), with greater mean body mass index (32.5 versus 31.6 kg/m2) and lower median estimated glomerular filtration rate (77.5 versus 84.0 ml/min/1.73 m2). Peripheral arterial disease and a history of myocardial infarction were more frequent in men (20.1% versus 11.7% and 12.0% versus 5.8%, respectively). At baseline, mean haemoglobin A1c (HbA1c) was 8.74% in men and 8.79% in women. Least square (LS) mean (95% CI) reduction in HbA1c from baseline to week 24 was − 1.17% (− 1.21 to − 1.13) in men and − 1.07% (− 1.11 to − 1.02) in women, resulting in a LS mean difference of − 0.10% (− 0.15 to − 0.05; p < 0.0001). At 24 weeks, 21.6% of women and 27.2% of men achieved target HbA1c of < 7.0% (p < 0.001; chi-square). Reported incidence for symptomatic (8.5% versus 8.7%) and severe (0.3% versus 0.5%) any-time-of-the-day or symptomatic (2.4% versus 1.8%) and severe (0.1% versus 0.2%) nocturnal hypoglycaemia was overall low and comparable between men and women. Changes in daily Gla-300 dose and body weight were also similar. // Conclusion: Despite some gender differences in baseline characteristics, Gla-300 treatment improved glycaemic control, with overall low hypoglycaemia incidences in both men and women. However, women had statistically significantly lower HbA1c reductions than men, although these differences were clinically modest

Glycaemic Control with Insulin Glargine 300 U/mL in Individuals with Type 2 Diabetes and Chronic Kidney Disease: A REALI European Pooled Data Analysis

INTRODUCTION: Management of type 2 diabetes mellitus (T2DM) in patients with chronic kidney disease is complex. Using the REALI European pooled database, we determined the impact of baseline renal function on the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) initiated in adults with inadequately controlled T2DM. METHODS: Data from 1712 patients with available estimated glomerular filtration rate (eGFR) at baseline were pooled from six 24-week prospective studies. Patients who received once-daily subcutaneous injections of Gla-300 were classified into four renal function subgroups, according to baseline eGFR: ≥ 90 (N = 599), 60–89 (N = 786), 45–59 (N = 219), and 15–44 mL/min/1.73 m2 (N = 108). RESULTS: Compared to those with baseline eGFR ≥ 60 mL/min/1.73 m2, patients with lower eGFR values tended to be older, had a longer T2DM duration, and were more likely to present diabetic complications. After 24 weeks of Gla-300 therapy, the least-squares mean (95% confidence interval) decrease in haemoglobin A1c (HbA1c) from baseline (− 1.14% [− 1.28 to − 1.00], − 1.21% [− 1.34 to − 1.08], − 1.19% [− 1.36 to − 1.01], and − 0.99% [− 1.22 to − 0.76]) and the proportion of patients achieving HbA1c < 7.5% (53.3%, 51.3%, 49.5%, and 51.5%) were comparable in the ≥ 90, 60–89, 45–59, and 15–44 mL/min/1.73 m2 subgroups, respectively. Although the incidence of hypoglycaemia was overall low, more patients in the eGFR 15–44 mL/min/1.73 m2 subgroup experienced hypoglycaemia at night or at any time of the day compared with higher eGFR subgroups. There were no notable differences between the renal function subgroups in the changes in Gla-300 daily dose and body weight from baseline to week 24. CONCLUSION: Although an eGFR of 15–44 mL/min/1.73 m2 was associated with a slightly increased risk of hypoglycaemia among patients with inadequately controlled T2DM, Gla-300 provided glycaemic improvement with an overall favourable safety profile regardless of baseline eGFR

Reduced hypoglycemia risk in type 2 diabetes patients switched to/initiating insulin glargine 300 vs 100 U/ml: A european real-world study

Introduction: Randomized controlled trials and real-world data from the USA have shown similar glycemic control with insulin glargine 300 U/ml (Gla-300) and insulin glargine 100 U/ml (Gla-100) and reduced hypoglycemia risk with Gla-300. This real-world study describes the efficacy and safety of Gla-300 and Gla-100 in patients with type 2 diabetes (T2D) in France, Spain, and Germany. Methods: This retrospective chart review analysis used anonymized data for adults with T2D switching basal insulin analog (BIA) therapy to Gla-300 or Gla-100, or insulin-naïve patients initiating Gla-300 or Gla-100. Outcomes included change from baseline to 6-month follow-up in glycated hemoglobin A1c (A1C), total and severe hypoglycemia incidences and events, insulin dose, and reasons for BIA choice. Results: Six hundred sixty-five physicians (33.8% Spain, 31.7% France, 34.4% Germany) provided chart data for patients switching to Gla-300 (n = 679) or Gla-100 (n = 429) or initiating Gla-300 (n = 719) or Gla-100 (n = 711). After adjustment for baseline characteristics, A1C reductions from baseline were similar for patients switching to Gla-300 or Gla-100 (- 0.87% vs. - 0.93%; p = 0.326) while those switched to Gla-300 vs. Gla-100 had a significantly greater mean reduction in hypoglycemic events (- 1.29 vs. - 0.81 events during 6 months; p = 0.012). Mean insulin doses after titration were 0.43 ± 0.36 and 0.40 ± 0.28 U/kg in Gla-300 and Gla-100 switchers, respectively. Factors that significantly influenced BIA choice included a lower risk of hypoglycemia (for Gla-300) and physician familiarity (for Gla-100). Outcomes for insulin-naïve patients were broadly similar to those of switchers. Conclusions: In this real-world European study, patients with T2D who switched therapy to Gla-300 or Gla-100 had improved glycemic control and reduced hypoglycemia at 6 months, with significant hypoglycemia advantages with Gla-300

Impact of Age on the Effectiveness and Safety of Insulin Glargine 300 U/mL: Results from the REALI European Pooled Data Analysis

Introduction: Patients aged ≥ 65 years continue to be underrepresented in clinical studies related to type 2 diabetes mellitus (T2DM). Accordingly, the REALI pooled analysis was performed to evaluate the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) across different age subgroups, using data from 14 interventional and non-interventional studies. Methods: Pooled efficacy and safety data were collected from 8106 European patients with uncontrolled T2DM who were initiated on or switched to Gla-300 injected once daily for 24 weeks. Patients were categorised into five age subgroups: < 50 (N = 727), 50–59 (N = 2030), 60–69 (N = 3054), 70–79 (N = 1847) and ≥ 80 years (N = 448). Results: Mean baseline haemoglobin A1c (HbA1c) decreased linearly from the youngest (9.10%) to the oldest (8.46%) age subgroup. Following Gla-300 initiation, there were similar HbA1c reductions across age groups, with a least squares mean (95% confidence interval) change in HbA1c from baseline to week 24 of − 1.09% (− 1.18 to − 1.00), − 1.08% (− 1.14 to − 1.03), − 1.12% (− 1.17 to − 1.07), − 1.18% (− 1.24 to − 1.12) and − 1.11% (− 1.23 to − 0.99) in the < 50, 50–59, 60–69, 70–79 and ≥ 80 years subgroups, respectively. The incidences and event rates of reported hypoglycaemia were overall low. Compared to younger age subgroups, lower incidences of symptomatic hypoglycaemia occurring at any time of the day (5.9 vs. 7.6–9.4% for the younger subgroups) or during the night (0.5 vs. 1.6–2.5%) were recorded in patients aged ≥ 80 years. By contrast, the highest incidence of severe hypoglycaemia occurring any time of the day was reported in the subgroup aged ≥ 80 years (1.1 vs. 0.1–0.6% for the younger age subgroups). Conclusion: Gla-300 initiated in patients with uncontrolled T2DM provides glycaemic improvement with a favourable safety profile across a wide range of ages

Glycaemic Control with Insulin Glargine 300 U/mL in Individuals with Type 2 Diabetes and Chronic Kidney Disease: A REALI European Pooled Data Analysis

Introduction: Management of type&nbsp;2 diabetes mellitus (T2DM) in patients with chronic kidney disease is complex. Using the REALI European pooled database, we determined the impact of baseline renal function on the effectiveness and safety of insulin glargine 300&nbsp;U/mL (Gla-300) initiated in adults with inadequately controlled T2DM. Methods: Data from 1712 patients with available estimated glomerular filtration rate (eGFR) at baseline were pooled from six 24-week prospective studies. Patients who received once-daily subcutaneous injections of Gla-300 were classified into four renal function subgroups, according to baseline eGFR: ≥ 90 (N = 599), 60–89 (N = 786), 45–59 (N = 219), and 15–44&nbsp;mL/min/1.73&nbsp;m2 (N = 108). Results: Compared to those with baseline eGFR ≥ 60&nbsp;mL/min/1.73&nbsp;m2, patients with lower eGFR values tended to be older, had a longer T2DM duration, and were more likely to present diabetic complications. After 24&nbsp;weeks of Gla-300 therapy, the least-squares mean (95% confidence interval) decrease in haemoglobin A1c (HbA1c) from baseline (−&nbsp;1.14% [−&nbsp;1.28 to −&nbsp;1.00], −&nbsp;1.21% [−&nbsp;1.34 to −&nbsp;1.08], −&nbsp;1.19% [−&nbsp;1.36 to −&nbsp;1.01], and −&nbsp;0.99% [−&nbsp;1.22 to −&nbsp;0.76]) and the proportion of patients achieving HbA1c &lt; 7.5% (53.3%, 51.3%, 49.5%, and 51.5%) were comparable in the ≥ 90, 60–89, 45–59, and 15–44&nbsp;mL/min/1.73&nbsp;m2 subgroups, respectively. Although the incidence of hypoglycaemia was overall low, more patients in the eGFR 15–44&nbsp;mL/min/1.73&nbsp;m2 subgroup experienced hypoglycaemia at night or at any time of the day compared with higher eGFR subgroups. There were no notable differences between the renal function subgroups in the changes in Gla-300 daily dose and body weight from baseline to week&nbsp;24. Conclusion: Although an eGFR of 15–44&nbsp;mL/min/1.73&nbsp;m2 was associated with a slightly increased risk of hypoglycaemia among patients with inadequately controlled T2DM, Gla-300 provided glycaemic improvement with an overall favourable safety profile regardless of baseline eGFR