Evaluating glucose‐lowering treatment in older people with diabetes : lessons from the IMPERIUM trial

Understanding the benefits and risks of treatments to be used by older individuals (≥65 years old) is critical for informed therapeutic decisions. Glucose‐lowering therapy for older patients with diabetes should be tailored to suit their clinical condition, comorbidities and impaired functional status, including varying degrees of frailty. However, despite the rapidly growing population of older adults with diabetes, there are few dedicated clinical trials evaluating glucose‐lowering treatment in older people. Conducting clinical trials in the older population poses multiple significant challenges. Despite the general agreement that individualizing treatment goals and avoiding hypoglycaemia is paramount for the therapy of older people with diabetes, there are conflicting perspectives on specific glycaemic targets that should be adopted and on use of specific drugs and treatment strategies. Assessment of functional status, frailty and comorbidities is not routinely performed in diabetes trials, contributing to insufficient characterization of older study participants. Moreover, significant operational barriers and problems make successful enrolment and completion of such studies difficult. In this review paper, we summarize the current guidelines and literature on conducting such trials, as well as the learnings from our own clinical trial (IMPERIUM) that assessed different glucose‐lowering strategies in older people with type 2 diabetes. We discuss the importance of strategies to improve study design, enrolment and attrition. Apart from summarizing some practical advice to facilitate the successful conduct of studies, we highlight key gaps and needs that warrant further research

Biological aspects of heterogeneous blood structure and its role in atherogenesis

Krew stanowi układ dwufazowy pośredni między zawiesiną i emulsją. Obecność erytrocytów oraz ich wzajemne oddziaływanie powoduje nadawanie krwi własności nienewtonowskich, determinujących hydrodynamikę i funkcje biologiczne krwi. Heterofazowa struktura krwi ma istotne znaczenie w powstawaniu zmian miażdżycowych, prowadzących do zwężenia tętnic. Tworzą się one w miejscach powstawania przepływów zaburzonych, gdzie krwiopochodne cząsteczki przechodzą do ściany tętnicy inicjując powstawanie złogów.Blood is a two-phase medium situated between suspension and emulsion. The presence of erythrocytes and their interaction gives blood non-Newtonian properties, which determine the hydrodynamics and biological functions of blood. The two-phase blood structure plays an essential role in the formation of atherosclerotic plaques which leads subsequently to arterial stenosis. Plaques preferentially develops at specific sites with disturbed flow, where the blood-borne particles penetrate the arterial wall initiating plaque formation

Resource use and costs of exenatide bid or insulin in clinical practice: the European CHOICE study

Urpo Kiiskinen,1 Stephan Matthaei,2 Matthew Reaney,3 Chantal Mathieu,4 Claes-G&ouml;ran &Ouml;stenson,5 Thure Krarup,6 Michael Theodorakis,7,* Jacek Kiljanski,8 Carole Salaun-Martin,9 H&eacute;l&egrave;ne Sapin,9 Bruno Guerci10 1Eli Lilly, Helsinki, Finland; 2Quakenbr&uuml;ck Diabetes Center, Quakenbr&uuml;ck, Germany; 3Eli Lilly, Windlesham, Surrey, UK; 4Department of Endocrinology, UZ Gasthuisberg, Leuven, Belgium; 5Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; 6Department of Endocrinology, Bispebjerg Hospital, Copenhagen, Denmark; 7Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece; 8Eli Lilly, Warsaw, Poland; 9Eli Lilly, Neuilly Cedex, France; 10Department of Diabetes, Metabolic Diseases, and Nutrition, H&ocirc;pital Brabois, Vandoeuvre-L&egrave;s-Nancy, France *Michael Theodorakis was affiliated with the institution shown above at the time of the study, but has since left this institution Purpose: CHOICE (CHanges to treatment and Outcomes in patients with type 2 diabetes initiating InjeCtablE therapy) assessed patterns of exenatide bid and initial insulin therapy usage in clinical practice in six European countries and evaluated outcomes during the study. Methods: CHOICE was a 24-month, prospective, noninterventional observational study. Clinical and resource use data were collected at initiation of first injectable therapy (exenatide bid or insulin) and at regular intervals for 24 months. Costs were evaluated from the national health care system perspective at 2009 prices. Results: A total of 2515 patients were recruited. At the 24-month analysis, significant treatment change had occurred during the study in 42.2% of 1114 eligible patients in the exenatide bid cohort and 36.0% of 1274 eligible patients in the insulin cohort. Improvements in glycemic control were observed over the course of the study in both cohorts (P < 0.001 for both), but mean weight was reduced in the exenatide bid cohort (P < 0.001) and increased in the insulin cohort (P < 0.001) by 24 months. Across all countries, total per patient health care costs for the 24 months post baseline were &euro;3997.9 in the exenatide bid cohort and &euro;3265.5 in the insulin cohort (&euro;1791.9 versus &euro;2465.5 due to costs other than those of injectable therapy). When baseline direct cost and patients&#39; and disease characteristics were controlled for, mean direct costs differed by country (P < 0.0001), irrespective of treatment initiated, and the mean cost difference between treatments varied by country (P < 0.0001). Conclusion: Much of the higher mean cost of exenatide bid, compared with insulin, therapy was compensated for by lower mean costs of other health service utilization. Costs associated with exenatide bid or insulin initiation varied across countries, highlighting the need to avoid generalization of resource use and cost implications of a particular therapy when estimated in specific country settings. Keywords: exenatide, health care costs, injectable therapy, insulin, resource use, type 2 diabetes mellitu