InsulinPub Date : 2009-01-01Epub Date: 2009-02-23DOI: 10.1016/S1557-0843(09)80004-3
Bo Ahrén MD, PhD (Professor)
{"title":"DPP-4 inhibitors","authors":"Bo Ahrén MD, PhD (Professor)","doi":"10.1016/S1557-0843(09)80004-3","DOIUrl":"https://doi.org/10.1016/S1557-0843(09)80004-3","url":null,"abstract":"<div><p>Inhibition of dipeptidyl peptidase 4 (DPP-4) is a novel treatment for type-2 diabetes. DPP-4 inhibition prevents the inactivation of glucagon-like peptide I (GLP-I), which increases levels of active GLP-I. This increases insulin secretion and reduces glucagon secretion, thereby low-ering glucose levels. Several DPP-4 inhibitors are in clinical development. Most experience so far has been with sitagliptin (Merck; approved by the FDA) and vildagliptin (Novartis; filed). These are orally active compounds with a long duration, allowing once-daily administration. Both sitagliptin and vildagliptin improve metabolic control in type-2 diabetes, both in monotherapy and in combination with metformin and thiazolidinediones. A reduction in HbA<sub>Ic</sub> of approximately 1% is seen in studies of DPP-4 inhibition of up to 52 weeks' duration. DPP-4 inhibition is safe and well tolerated, the risk of hypoglycaemia is minimal, and DPP-4 inhibition is body-weight neutral. DPP-4 inhibition is suggested to be a first-line treatment of type-2 diabetes, particularly in its early stages in combination with metformin. However, the durability and long-term safety of DPP-4 inhibition remain to be established.</p></div>","PeriodicalId":100678,"journal":{"name":"Insulin","volume":"4 1","pages":"Pages 15-31"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1557-0843(09)80004-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137350253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
InsulinPub Date : 2009-01-01Epub Date: 2009-02-23DOI: 10.1016/S1557-0843(09)80003-1
Paul S. Jellinger MD, MACE
{"title":"Metabolic consequences of hyperglycemia and insulin resistance","authors":"Paul S. Jellinger MD, MACE","doi":"10.1016/S1557-0843(09)80003-1","DOIUrl":"10.1016/S1557-0843(09)80003-1","url":null,"abstract":"<div><p>Insulin is a pleiotropic hormone that exerts a multitude of effects on metabolism and various cellular processes in the body. The main metabolic actions of insulin are to stimulate glucose uptake in skeletal muscle and the heart and to suppress the production of glucose and very-low-density lipoprotein in the liver. Other metabolic effects of insulin include inhibition of glucose release from the liver, inhibition of the release of free fatty acids (FFAs) from adipose tissue, and stimulation of the process by which amino acids are incorporated into protein. Insulin resistance (IR) is a condition in which defects in the action of insulin are such that normal levels of insulin do not trigger the signal for glucose absorption. An excess of FFAs is implicated in the pathogenesis of IR. The effects of this condition can have profound pathophysiologic effects on various organs and tissues of the body. For example, IR is associated with impaired insulin signaling, impaired fibrinolysis, and inflammation. The clinical consequences include hyperglycemia-induced tissue damage, hypertension, dyslipidemia, metabolic syndrome, and cardiovascular disease. Pharmacotherapies that target IR include metformin and the thiazolidinediones. Fndocannabinoid antagonists, agents that target obesity and associated cardiovascular and metabolic risk factors, are currently being developed.</p></div>","PeriodicalId":100678,"journal":{"name":"Insulin","volume":"4 1","pages":"Pages 2-14"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1557-0843(09)80003-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56830586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
InsulinPub Date : 2009-01-01Epub Date: 2009-02-23DOI: 10.1016/S1557-0843(09)80010-9
Anisha D. Patel DO, William V. Tamborlane MD
{"title":"“Diabetes tactics” case studies","authors":"Anisha D. Patel DO, William V. Tamborlane MD","doi":"10.1016/S1557-0843(09)80010-9","DOIUrl":"10.1016/S1557-0843(09)80010-9","url":null,"abstract":"","PeriodicalId":100678,"journal":{"name":"Insulin","volume":"4 1","pages":"Pages 75-78"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1557-0843(09)80010-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78437366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
InsulinPub Date : 2009-01-01Epub Date: 2009-02-23DOI: 10.1016/S1557-0843(09)80005-5
Julia M. Bottomley PhD (Managing Director) , Frank D. Raymond MBBS, PhD, MD (GP Principal)
{"title":"Pharmaco-economic issues for diabetes therapy","authors":"Julia M. Bottomley PhD (Managing Director) , Frank D. Raymond MBBS, PhD, MD (GP Principal)","doi":"10.1016/S1557-0843(09)80005-5","DOIUrl":"10.1016/S1557-0843(09)80005-5","url":null,"abstract":"<div><p>A systematic review was undertaken to analyse pharmaco-economic issues in diabetes, with evidence selected on the basis of relevance and immediacy. Pharmaco-economics in diabetes primarily relates to making choices about antidiabetic pharmaceuticals, and this is being influenced by global trends. Trends include increasing numbers of patients with diabetes, with increasing costs of caring for people with diabetes, and an ever-present focus on the costs of pharmaceuticals which are predicted to increase as the pace of development of new medications parallels the increasing incidence of the condition. These developments have influenced the demand for health care in diabetes in the last decade, and will continue to determine this in the coming decade. Recent national experiences are cited to illustrate current issues and to focus specifically upon the challenges facing a raft of new diabetes treatment options now hitting the marketplace, although supported by fewer completed long-term trials. It can be anticipated that these newer agents will be appraised for their cost-effectiveness or value for money. Economic analyses for some of the new technologies are summarized; in general, the peer-reviewed publications using well-accepted and validated models have reported thatthese technologies are cost-effective. Endorsement of any technology in a national setting is not awarded simply because the incremental cost-effectiveness ratio (ICER) falls below the threshold regarded as value for money. In most national observations the reviewers expressed concerns about assumptions used in economic modelling which resulted in the ICERs being deemed optimistic at best, generally highly uncertain, and resulting in the cost-effectiveness appearing better than it really would be in clinical practice. This has often led to the authorities concluding that the price advantage of new technologies over comparators could not be justified, essentially leading to restrictions in use compared to their licence. In general, a paucity of robust evidence on longer-term outcome data together with a lack of health-related quality of life (HRQOL) data collected in a reliable manner in appropriate patients and amenable to utility (and hence quality adjusted life year or QALY) estimation have resulted in problems for these new drugs atthe so-called fourth (cost-effectiveness) hurdle. In the light of these findings, the implications for generating credible fit-for-purpose cost-effectiveness analyses of new technologies in diabetes are discussed. Throughout this chapter, the interested reader is referred to a number of excellent review articles for further details.</p></div>","PeriodicalId":100678,"journal":{"name":"Insulin","volume":"4 1","pages":"Pages 32-60"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1557-0843(09)80005-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81310274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
InsulinPub Date : 2009-01-01Epub Date: 2009-02-23DOI: 10.1016/S1557-0843(09)80006-7
Helen Cooper , Katie Booth , Geoff Gill
{"title":"A trial of empowerment-based education in type 2 diabetes—Global rather than glycaemic benefits","authors":"Helen Cooper , Katie Booth , Geoff Gill","doi":"10.1016/S1557-0843(09)80006-7","DOIUrl":"10.1016/S1557-0843(09)80006-7","url":null,"abstract":"<div><p>We have assessed the effect of a structured, empowerment-based educational system (“LAY or “Look After Yourself”) for patients with type 2 diabetes. A randomised controlled trial (RCT) was conducted, testing the system against standard support. Using 3 centres, 89 patients participated in the study. Outcome measures included glycated haemoglobin (HbA<sub>1c</sub>), body mass index (BMI) and a variety of quantitative psychological and educational measures. Assessment was made at 6 months (“short-term”) and 12 months (“long-term”) post-intervention. The educational programme was associated with benefits in HbA<sub>1c</sub> levels (<em>p</em> = 0.005), illness attitudes (<em>p</em> = 0.04), and perceived treatment effectiveness (<em>p</em> = 0.03) at 6 months follow-up compared to controls. At 12 months however, only illness attitudes (<em>p</em> = 0.01), and self-monitoring (<em>p</em> = 0.002) showed benefit. A combined outcome measure showed positive benefit for the educational programme both at 6 months (<em>p</em> = 0.001) and 12 months (<em>p</em> = 0.002). This structured educational programme, aimed at encouraging selfhelp, was associated with only limited benefits in glycaemic control, but there were significant educational and psychological benefits. Diabetes education should be regarded as having broad patient-based positive outcomes, and should not be expected to have lasting benefits on glycaemic control.</p></div>","PeriodicalId":100678,"journal":{"name":"Insulin","volume":"4 1","pages":"Pages 61-67"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1557-0843(09)80006-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75379972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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