Insulin lispro low mixture twice daily versus basal insulin glargine once daily and prandial insulin lispro once daily in patients with type 2 diabetes requiring insulin intensification: A randomized phase IV trial
Tinahones F.J.,CIBER ISCIII |
Onaca A.,Pelican Hospital of Oradea |
Cleall S.,Eli Lilly and Company |
Rodriguez A.,Lilly Spain
Diabetes, Obesity and Metabolism | Year: 2014
Aims: To compare the efficacy and safety of two insulin intensification strategies in patients with type 2 diabetes inadequately controlled on basal insulin glargine with metformin and/or pioglitazone. Methods: A multinational, randomized, open-label trial that compared insulin lispro low mixture (LM25; n=236) twice daily with a basal-prandial regimen of insulin glargine once daily and insulin lispro once daily (IGL; n=240) over 24weeks in patients with HbA1c 7.5-10.5% and fasting plasma glucose =6.7 mmol/l. The primary objective was to assess non-inferiority [per-protocol (PP) population], and then superiority [intention-to-treat (ITT) population], of LM25 versus IGL according to change in HbA1c after 24weeks (non-inferiority margin 0.4%, two-sided significance level 0.05). Results: Estimated change [least squares (LS) mean (95% CI)] in HbA1c after 24 weeks: -1.30 (-1.44, -1.16)% with LM25 and -1.08 (-1.22, -0.94)%with IGL. Non-inferioritywas shown [LSmean (95% CI) HbA1c treatment difference-0.21 (-0.38,-0.04) (PP population)]; gated superiority assessment showed a statistically significant advantage for LM25 (p=0.010; ITT population). Mean blood glucose, glycaemic variability, overall tolerability and hypoglycaemic episodes per patient-year did not show significant differences between treatments during the study. Conclusions: In patients with type 2 diabetes inadequately controlled on once-daily basal insulin glargine and metformin and/or pioglitazone, intensification with LM25 was superior to a basal-prandial approach in terms of reduction in HbA1c after 24 weeks and did not increase hypoglycaemia episodes. © 2014 John Wiley & Sons Ltd.
PubMed | National Association of Health Journalists, FEDER Spanish Federation for Rare Diseases, Clinical Open Innovation, Hospital Ramon y Cajal and 3 more.
Type: | Journal: Patient preference and adherence | Year: 2016
The development of a patient-centered approach to medicine is gradually allowing more patients to be involved in their own medical decisions. However, this change is not happening at the same rate in clinical research, where research generally continues to be carried out on patients, but not with patients. This work describes the why, when, and how of more active patient participation in the research process. Specific measures are proposed to improve patient involvement in 1) setting priorities, 2) study leadership and design, 3) improved access to clinical trials, 4) preparation and oversight of the information provided to participants, 5) post-study evaluation of the patient experience, and 6) the dissemination and application of results. In order to achieve these aims, the relative emphases on the ethical principles underlying research need to be changed. The current model based on the principle of beneficence must be left behind, and one that upholds the ethical principles of autonomy and non maleficence should be embraced. There is a need to improve the level of information that patients and society as a whole have on research objectives and processes; the goal is to promote the gradual emergence of the expert patient.
Insulin lispro low mixture twice daily vs basal insulin glargine once daily and prandial insulin lispro once daily as insulin intensification strategies in patients with type 2 diabetes: Latin American subpopulation analysis of a randomized trial
PubMed | Head en Institute Investigaciones Clinicas, Lilly Spain and Eli Lilly and Company
Type: | Journal: Diabetology & metabolic syndrome | Year: 2016
This post hoc analysis examined the efficacy and safety of twice-daily insulin lispro low mixture (LM25) and once-daily basal insulin glargine plus once-daily prandial insulin lispro (IGL) in a Latin American subpopulation with type 2 diabetes mellitus (T2DM).A phase 4, randomized, open-label, parallel-arm trial included participants aged 18-75years with T2DM taking once-daily insulin glargine and stable doses of metformin and/or pioglitazone with glycated hemoglobin (HbA1c) 7.5-10.5% and fasting plasma glucose121mg/dL. Participants were randomized 1:1 to receive their stable dose of metformin and/or pioglitazone plus twice-daily LM25 or IGL for 24weeks. The primary efficacy outcome was change in HbA1c after 24weeks of treatment. Results from participants in Argentina, Brazil, and Mexico are presented here.162 participants (80 LM25; 82 IGL) with meanstandard deviation (SD) age=57.39.0years and body mass index=31.35.2kg/m(2) were included. MeanSD change in HbA1c from baseline to week 24 was -1.51.0% (LM25) and -1.11.2% (IGL). At week 24, 35.1% (LM25) and 31.6% (IGL) of participants achieved HbA1c<7.0%. MeanSD weight gain from baseline to week 24 was 2.42.9kg in the LM25 group and 1.03.1kg in the IGL group. The meanSD rates of total hypoglycemia per year were 18.927.3 (LM25) and 21.631.1(IGL). Rates of treatment-emergent adverse events were 46% (LM25) and 39% (IGL).Our results suggest that both LM25 and IGL are viable treatment options for insulin intensification in Latin American patients with T2DM with suboptimal glycemic control on basal insulin glargine. The safety and tolerability profiles of LM25 and IGL are consistent between this Latin American population and the global trial-level population. Trial registration NCT01175824.
Sacristan J.A.,Lilly Spain |
Avendano-Sola C.,Hospital Universitario Puerta Of Hierro
International Journal of Clinical Practice | Year: 2015
Three decades ago, John R Hampton announced the death of clinical freedom. Since then, evidence-based medicine has been the predominant paradigm in clinical research. By applying a population-based approach, the randomised controlled trial has become the cornerstone for demonstrating the overall effect of a treatment and for developing guidelines. The new patient-centred medicine movement is rediscovering the important implications of heterogeneity of treatment effects for clinical practice and that a better understanding of such variability can contribute to improve health outcomes for individual patients through practicing a science-based clinical freedom. © 2015 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.
Blanco R.,Oncology Service |
Maestu I.,Hospital Universitario Dr Peset |
de la Torre M.G.,Lilly Spain |
Cassinello A.,Lilly Spain |
Nunez I.,Lilly Spain
Annals of Oncology | Year: 2015
Most patients with non-small-cell lung cancer (NSCLC) are elderly but evidence to guide appropriate treatment decisions for this age group is generally scant. Careful evaluation of the elderly should be undertaken to ensure that treatment appropriate for the stage of the tumour is guided by patient characteristics and not by age. The Comprehensive Geriatric Assessment (CGA) remains the preferred option, but briefer tools may be appropriate to select patients for further evaluation. The predicted outcome should be used to guide management decisions together with a reappraisal of polypharmacy. Patient expectations should also be taken into account. Management recommendations are generally similar to those of general guidelines for the NSCLC population, although the risks of surgery and toxicity of chemotherapy and radiotherapy are often increased in the elderly compared with younger patients; therefore, patients should be closely scrutinised and subjected to a CGA to ensure suitability of the planned treatment. If surgery is indicated, then lobectomy is generally the preferred option, although limited resection may be more feasible for some. Radiotherapy with curative intent is an alternative, with stereotactic body radiotherapy the most likely preferred modality. Adjuvant chemotherapy is also an appropriate approach, whereas adjuvant radiotherapy is generally not recommended. Concurrent chemoradiotherapy should be considered for elderly patients with inoperable locally advanced disease and chemotherapy for advanced/metastatic disease. Efforts should also be made to increase participation of elderly patients with NSCLC in clinical trials, thereby enhancing evidence-based treatment decisions for this majority group. This will require overcoming barriers relating to trial design and to physician and patient awareness and attitudes. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
Roussel R.,Groupe Hospitalier Bichat Claude Bernard |
Roussel R.,French Institute of Health and Medical Research |
Roussel R.,University Paris Diderot |
Lorraine J.,Eli Lilly and Company |
And 2 more authors.
Advances in Therapy | Year: 2015
Introduction: It can be a challenge to manage glycemic control in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), due to both patient and medication issues. Although most antihyperglycemic medications can be used in mild kidney disease, many medications are either not advised or require dose adjustments in more advanced CKD. This review summarizes product label information, pharmacokinetic and clinical studies, and clinical guidelines relevant to use of antihyperglycemic medications in CKD. Methods: Product labels and guidelines from North America and Europe, as well as pharmacokinetic and clinical studies of diabetes medication use in CKD were identified through Medline and PubMed searches, up to February 2015. Available data are summarized and correlations between treatment recommendations and available research are discussed, as are glycemic targets for patients with CKD. Results: Newer medications have significantly more data available than older medications regarding use in CKD, although larger clinical studies are still lacking for some drugs. As CKD advances, dose adjustment is needed for many medications [numerous dipeptidyl peptidase-4 inhibitors, some insulins, sodium glucose co-transporter 2 (SGLT2) inhibitors], although not for others (thiazolidinediones, meglitinides). Some medications are not recommended for use in more advanced CKD (metformin, SGLT2 inhibitors, some glucagon-like protein-1 receptor agonists) for safety or efficacy reasons. There is not always good alignment between label recommendations, pharmacokinetic or clinical studies, and guideline recommendations for use of these drugs in CKD. In particular, controversy remains about the use of metformin in moderate CKD and appropriate use of liraglutide and sulfonylureas in advanced CKD. Conclusion: Considerable variability exists with respect to recommendations and clinical data for the many antihyperglycemic drugs used in patients with T2DM and CKD. Funding: Eli Lilly and Company. © 2015, Springer Healthcare.
PubMed | Eli Lilly and Company, Lilly Spain and Groupe Hospitalier Bichat Claude Bernard
Type: Journal Article | Journal: Advances in therapy | Year: 2015
It can be a challenge to manage glycemic control in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), due to both patient and medication issues. Although most antihyperglycemic medications can be used in mild kidney disease, many medications are either not advised or require dose adjustments in more advanced CKD. This review summarizes product label information, pharmacokinetic and clinical studies, and clinical guidelines relevant to use of antihyperglycemic medications in CKD.Product labels and guidelines from North America and Europe, as well as pharmacokinetic and clinical studies of diabetes medication use in CKD were identified through Medline and PubMed searches, up to February 2015. Available data are summarized and correlations between treatment recommendations and available research are discussed, as are glycemic targets for patients with CKD.Newer medications have significantly more data available than older medications regarding use in CKD, although larger clinical studies are still lacking for some drugs. As CKD advances, dose adjustment is needed for many medications [numerous dipeptidyl peptidase-4 inhibitors, some insulins, sodium glucose co-transporter 2 (SGLT2) inhibitors], although not for others (thiazolidinediones, meglitinides). Some medications are not recommended for use in more advanced CKD (metformin, SGLT2 inhibitors, some glucagon-like protein-1 receptor agonists) for safety or efficacy reasons. There is not always good alignment between label recommendations, pharmacokinetic or clinical studies, and guideline recommendations for use of these drugs in CKD. In particular, controversy remains about the use of metformin in moderate CKD and appropriate use of liraglutide and sulfonylureas in advanced CKD.Considerable variability exists with respect to recommendations and clinical data for the many antihyperglycemic drugs used in patients with T2DM and CKD.Eli Lilly and Company.
Clinical course after five years of insulin therapy in patients with type 2 diabetes in Spain: Results of the EDIN study [Evolución clínica a 5 años desde el inicio de la insulinoterapia en pacientes con diabetes tipo 2 en España: Resultados del estudio EDIN]
Rodriguez A.,Lilly Spain |
Tofe S.,Hospital Universitario Son Espases |
Reviriego J.,Lilly Spain
Endocrinologia y Nutricion | Year: 2014
Objectives: The primary study objective was to assess the proportion of patients with type 2 diabetes and an HbA1c value ≤6.5% from the start of insulin therapy to five years later in the outpatient setting in Spain. Material and methods: This was an observational, multicenter, naturalistic study with retrospective collection of clinical data. Investigators were endocrinologists or internal medicine specialists from all over Spain. During standard clinical care, patients started insulin therapy, which was continued for at least 5 years. Results: The clinical records of 405 patients were reviewed. The final analysis set included records from 346 patients. At baseline (start of insulin therapy), 51.2% of patients were female; mean (SD) age was 64.6 (9.0) years; body mass index, 29.8 (4-5) kg/m2; time since diagnosis, 8.8 (6.8) years; HbA1c, 9.4% (1.5); fasting glucose, 223.7 (55.9) mg/dL; and mean 2-hour postprandial glucose, 293.6 (71.0) mg/dL. When insulin therapy was started, <1.0% of patients had an HbA1c value ≤6.5%. At 5 years, 10.3% of patients achieved the HbA1c goal of ≤6.5% (mean, 7.72%). All glucose parameters (HbA1c, fasting glucose, and 2-hour postprandial glucose) improved at 5 years as compared to values at the start of insulin therapy. Conclusions: Glucose parameters improved over time in patients with type 2 diabetes in this naturalistic study. However, blood glucose control exceeded the internationally recommended target values. These results therefore suggest that there is still some margin for improvement in outpatient care in Spain. © 2013 SEEN.
Sacristan J.A.,Lilly Spain
BMC Medical Research Methodology | Year: 2015
Background: Despite their close relationship, clinical research and medical care have become separated by clear boundaries. The purpose of clinical research is to generate generalizable knowledge useful for future patients, whereas medical care aims to promote the well-being of individual patients. The evolution towards patientcentered medicine and patient-oriented research, and the gradual standardization of medicine are contributing to closer ties between clinical research and medical practice. But the integration of both activities requires addressing important ethical and methodological challenges. Discussion: From an ethical perspective, clinical research should evolve from a position of paternalistic beneficence to a situation in which the principle of non-maleficence and patient autonomy predominate. The progressive adoption of "patient-oriented informed consent", "patient equipoise", and "altruism-based research", and the application of risk-based ethical oversight, in which the level of regulatory scrutiny is adapted to the potential risk for patients, are crucial steps to achieve the integration between research and care. From a methodological standpoint, careful and systematic observations should have greater relevance in clinical research, and experiments should be embedded into usual clinical practice. Clinical research should focus on individuals through the development of patient-oriented research. In a complementary way, the integration of experiments into medical practice through the systematic application of "point of care research" could help to generate knowledge for the individuals and for the populations. Summary: The integration of clinical research and medical care will require researchers, clinicians, health care managers, and patients to reevaluate the way they understand both activities. The development of an integrated learning health care system will contribute to generating and applying clinically relevant medical knowledge, producing benefits for present and future patients. © 2015 Sacristán; licensee BioMed Central.
Sacristan J.A.,Lilly Spain
BMC Medical Informatics and Decision Making | Year: 2013
Background: Patient-centered medicine is developing alongside the concepts of personalized medicine and tailored therapeutics. The main objective of patient-centered medicine is to improve health outcomes of individual patients in everyday clinical practice, taking into account the patient's objectives, preferences, values as well as the available economic resources. Discussion. Patient-centered medicine implies a paradigm shift in the relationship between doctors and patients, but also requires the development of patient-oriented research. Patient-oriented research should not be based on the evaluation of medical interventions in the average patient, but on the identification of the best intervention for every individual patient, the study of heterogeneity and the assignment of greater value to observations and exceptions. The development of information-based technologies can help to close the gap between clinical research and clinical practice, a fundamental step for any advance in this field. Summary. Evidence-based medicine and patient centered medicine are not contradictory but complementary movements. It is not possible to practice patient-centered medicine that is not based on evidence, nor is it possible to practice evidence-based medicine at a distance from the individual patient. © 2013 Sacristán; licensee BioMed Central Ltd.