Effectiveness, Simplification and Persistence of IDegLira in Poorly Controlled People with Type 2 Diabetes: A 4-Year Follow-Up Real-World Study.

INTRODUCTION: Efficacy and safety of the fixed ratio combination of insulin degludec and liraglutide (IDegLira) has been largely documented. However, long-term data are limited. This study aimed at describing persistence in therapy and the effectiveness at 48 months of IDegLira. METHODS: We conducted an observational study based on retrospective chart review. All patients treated with IDegLira during 2018-2022 were included. Data on treatment approaches and clinical outcomes were collected at the first prescription of IDegLira (T0) and after 6, 12, 24, 36, and 48 months. RESULTS: Overall, 156 patients (mean age 68 years, 64.1% men) started IDegLira, of whom 88 (56.4%) were previously treated with basal-oral therapy (BOT) and 68 (43.6%) with basal-bolus schemes (BB). Before starting IDegLira, 23.8% were treated with ≥ 2 oral antihyperglycemic agents in association with insulin; at T0, the proportion decreased to 3.2%. Short-acting insulin was discontinued after the first week. After 48 months, levels of HbA1c were significantly reduced by 1.34% in the BOT group and 1.07% in the BB group (p < 0.0001 in both groups). In the BOT group, FBG levels decreased by about 50 mg/dl and body weight was unchanged. In the BB group, FBG levels decreased by about 40 mg/dl and body weight was significantly reduced by an average of 7.7 kg. Five patients (3.2%) interrupted therapy with IDegLira during 48 months, and no severe hypoglycemia occurred. CONCLUSIONS: Our study emphasizes the important role of IDegLira in maintaining a good metabolic control while minimizing the risk of major hypoglycemia and weight gain in the long term. The substantial simplification of treatment schemes can increase adherence.

Effectiveness in Real World of Once Weekly Semaglutide in People with Type 2 Diabetes: Glucagon-Like Peptide Receptor Agonist Naïve or Switchers from Other Glucagon-Like Peptide Receptor Agonists: Results from a Retrospective Observational Study in Umbria.

INTRODUCTION: To complement results of the SUSTAIN program, this study assessed effectiveness and safety of once weekly subcutaneous semaglutide in people with type 2 diabetes (T2D) managed under routine care. METHODS: This was a multicenter, observational, retrospective study including all patients treated with semaglutide. Changes in clinical outcomes from baseline to 6 and 12 months were assessed in patients who were glucagon-like peptide receptor agonist (GLP-1RA) naïve or switching from another GLP-1RA. Discontinuation rate was assessed. RESULTS: Overall, 216 patients (mean age 64 years, 65.7% men) were evaluated: 135 (61.5%) naïve and 81 (38.5%) switchers from another GLP-1RA. In the naïve cohort, after 6 months from semaglutide initiation, levels of HbA1c significantly decreased by - 1.31% (p < 0.0001). All obesity indices improved, with mean reductions in body weight of - 3.92 kg, in BMI of - 1.43 kg/m2, and in waist circumference of - 5.03 cm. In the switcher cohort, statistically significant improvements in HbA1c (- 0.78%), body weight (- 2.64 kg), and waist circumference (- 3.03 cm) were obtained after 6 months. Reductions were sustained after 12 months in both cohorts (mean semaglutide dose: 0.86 mg in naïve and 0.96 mg in switcher cohort). Blood pressure and lipid profile mean levels decreased after 12 months from semaglutide initiation in both cohorts. No severe hypoglycemia occurred; 6.5% of patients discontinued semaglutide (2.8% due to gastrointestinal side effects). CONCLUSION: Effectiveness and tolerability of semaglutide have been confirmed in the real world irrespective of diabetes duration and severity. As expected, more marked reductions in HbA1c and obesity indices were obtained in naïve patients, but it is noteworthy that relevant improvements were also obtained in patients already treated with GLP-1RAs.

Switching Patients with Type 1 Diabetes to Insulin Degludec from Other Basal Insulins: Real-World Data of Effectiveness and Safety.

INTRODUCTION: Real-world evidence on the effectiveness and safety of insulin degludec (IDeg) in patients with diabetes is a priority. We have therefore evaluated the effectiveness and safety of IDeg, including impact on metabolic control, glycemic variability, weight gain and hypoglycemia, in patients with type 1 diabetes under routine clinical practice conditions. METHODS: This was an observational longitudinal multicenter study. A retrospective chart review of all patients with type 1 diabetes who were switched from basal insulin to IDeg was performed, and temporal trends in clinical outcomes were assessed. RESULTS: Data obtained from 195 patients, with a median age of 42.8 [interquartile range (IQR) 24.6-56.4] years and a median diabetes duration of 16 (IQR 10.0-28) years, were analyzed. Median follow-up was 9.5 (IQR 7.7-11.3) months. Improvements were found in glycated hemoglobin (- 0.34%; p < 0.0001), fasting blood glucose (- 24.82 mg/dL; p < 0.0001), post-prandial glucose (- 17.23 mg/dL; p = 0.0009), glycemic variability as indicated by standard deviation of blood glucose (- 5.67 mg/dL; p < 0.0001) and high blood glucose index (- 3.77; p < 0.0001). Body weight and body mass index remained substantially stable during the follow-up (- 0.18 kg; p = 0.56 and - 0.12; p = 0.42, respectively). Risk of nocturnal hypoglycemia decreased by 52% [incidence rate ratio 0.48; 95% confidence interval (CI) 0.29-0.77] and risk of total hypoglycemic episodes by 41% (incidence ratio 0.59; 95% CI 0.45-0.83). Basal and short-acting insulin doses decreased by - 1.4 and - 3.1 IU, respectively. CONCLUSION: Switching patients with type 1 diabetes to IDeg from other basal insulins was associated with relevant improvements in metabolic control and glycemic variability without weight gain; the risk of hypoglycemic episodes also significantly declined. FUNDING: Novo Nordisk S.p.A. unconditional grant.

Impact of Insulin Degludec in Type 2 Diabetes: Real-World Data on Effectiveness and Safety.

INTRODUCTION: Real-world evidence on effectiveness and safety of insulin degludec (IDeg) in patients with diabetes is a priority. The aim of the study was to evaluate patterns of use and the long-term effectiveness and safety of IDeg in routine clinical practice. METHODS: This was an observational longitudinal study. A retrospective chart review of all patients with type 2 diabetes treated with IDeg was performed and temporal trends in clinical outcomes were assessed. All data was stratified by treatment modality: the switch group consisted of patients already treated with another basal insulin before initiating IDeg; the add-on group consisted of basal insulin-naïve patients. RESULTS: Overall, 247 patients were analyzed (55 in the add-on group and 192 in the switch group), mean age 67.0 ± 10.9 years ,and diabetes duration 16.3 ± 8.9 years. Median (interquartile range) follow-up was 9.7 (8.0-11.9) months. In the add-on group, improvements were found in glycated hemoglobin (HbA1c) (- 1.68%; p < 0.0001), fasting blood glucose (FBG) (- 64.7 mg/dL; p < 0.0001), post-prandial glucose (PPG) (- 81.1 mg/dl; p < 0.0001), and glycemic variability (i.e., standard deviation of blood glucose) (- 11.6 mg/dl; p = 0.04). Even in the switch group, improvements were found in HbA1c (- 0.57%; p < 0.0001), FBG (- 28.1 mg/dL; p < 0.0001), and PPG (- 22.6 mg/dl; p = 0.001). Body weight increase during the follow-up was not statistically significant vs. baseline in both groups. Benefits on overall, nocturnal, and severe hypoglycemia were found in the switch group. CONCLUSION: These real-world data documented that initiating IDeg or switching to IDeg from other basal insulins in type 2 diabetes was associated with significant improvement in metabolic control without significant weight gain; a decrease in the risk of hypoglycemia was observed when switching to IDeg from another basal insulin.

Effects of vitamin C and aspirin in ischemic stroke-related lipid peroxidation: results of the AVASAS (Aspirin Versus Ascorbic acid plus Aspirin in Stroke) Study.

A condition of oxidative stress is known to occur in ischemic stroke, the current therapeutic intervention of which is largely limited to thrombolysis. To assess the effect of vitamin C - in conjunction to aspirin - in ischemic stroke-related lipid peroxidation, we measured plasma levels of ascorbate, of 8,12-isoprostanes F2alpha-VI (8,12-iPF2alpha-VI) and activities and levels of a broad spectrum of antioxidant enzymes and micronutrients in stroke patients randomized to receive, from stroke onset and up to three months, either vitamin C (200 mg/day) plus aspirin (300 mg/day) or only aspirin (300 mg/day). By the end of the first week, patients treated with vitamin C plus aspirin had higher vitamin C levels (p = 0.02) and lower 8,12-iPF2alpha-VI levels (p = 0.01) than patients treated with aspirin alone. The significance was maintained for the increase of vitamin C after three months of therapy (p < 0.01). The clinical functional outcome for both groups of patients similarly ameliorated after three months of treatment. We conclude that vitamin C, at the dose of 200 mg/day and in conjunction with aspirin, significantly decreases ischemic stroke-related lipid peroxidation in humans. Further studies are warranted to clarify whether the use of vitamin C may add clinical long-term beneficial effects in patients with stroke.

Lack of association of CCR2-64I and CCR5-Delta 32 with type 1 diabetes and latent autoimmune diabetes in adults.

It is well known that type 1 diabetes mellitus (T1DM) is a complex genetic disease resulting from the autoimmune destruction of pancreatic beta cells. Several genes have been associated with susceptibility and/or protection for T1DM, but the disease risk is mostly influenced by genes located in the class II region of the major histocompatibility complex. The attraction of leukocytes to tissues is essential for inflammation and the beginning of autoimmune reaction. The process is controlled by chemokines, which are chemotactic cytolines. Some studies have shown that CCR2-64I and CCR5-Delta 32 might be important for protection of susceptibility to some immunologically-mediated disorders. In the present study, we demonstrate the lack of association between CCR2-64I and CCR5-Delta 32 gene polymorphism and TIDM and we describe a new method for a simple and more precise genotyping of the CCR2 gene.