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Present Therapies of Type 2 Diabetes Mellitus ACP Annual Session MTP 057&058 San Francisco, CA April 15-16, 2005 Edward S. Glycemia in Relation to Microvascular Disease and MI 80 MIMicrovascular disease 60 er t-years ce p en atien 40 cid In 1,000 p 20 0 0 5 6 7 8 9 10 11 Updated mean HbA (%) 1C UKPDS 35.
THUS… A major goal of treatment of pre-diabetes and diabetes is to prevent both the micro- and macrovascular complications! ?-cell Function in the UKPDS 100 90 ) 80 (% 70 n 60 ctio n 50 u 40 30 ?-cell F 2010 0 –12 –10 –8 –6 –4 –2 0 2 4 6 Years From Diagnosis UKPDS = United Kingdom Prospective Diabetes Study.Holman RR et al. 3 year incidence (%) of components by treatment group Placebo Metformin Lifestyle Waist Circ.
Questions For Discussion ? Can Lifestyle Modification Interventions be implemented successful y? New Trends in Dietary Management There is much current interest in LOW CHO, LOW FAT and HIGH PROTEIN diets, but only limited data in humans to date.
Glucagon-Like Peptide-1 (GLP-1) • Product of the proglucagon gene from intestinal L-cel s• Release is rapid in response to meals• Potent insulinotropic hormone• Impaired glucose tolerance (IGT) and type 2 diabetes manifest with lower plasma GLP-1 compared to healthy controls Toft-Nielsen M, et al. GLP-1 secretion and metabolism Mixed Meal GLP-1(9-36) Intestinal Inactive GLP-1 DPP-IV Release GLP-1(7-36) Rapid Inactivation Active (>80% of pool) Plasma GLP-1 Actions Renal Clearance DPP-IV = didpeptidylpeptidase-IV Deacon et al. GLP-1 Modes of Action in Humans Upon ingestion of food… • Stimulates glucose-dependent insulin secretion • Suppresses glucagon secretion • Slows gastric emptying GLP-1 is secreted • Reduces food intake from the L-cells in the intestine • Improves insulin sensitivity Long term effects demonstrated in animals… This in turn… • Increases beta-cell mass and maintains beta-cell efficiency Drucker DJ. Localization of DPP-IV (Red) and GLP-1 (Green) in Human Gut Circumventing DPP-IV–mediated GLP-1 inactivation poses a major chal enge for drug development. Dipeptidylpeptidase 4 (DPP4) Inactivates Glucagon Like Peptide-1 (GLP-1) Mixed meal GLP-1 Intestinal Inactive GLP-1 release DPP-IV GLP-1 Rapid inactivation Active (>80% of pool) Plasma GLP-1 Actions Excreted by kidneys Deacon et al. Augmenting GLP-1 Levels by Inhibiting DPP-IV Activity Mixed meal GLP-1 Intestinal Inactive GLP-1 release DPP-IV GLP-1 Rapid inactivation (>80% of pool) Active Plasma GLP-1 Actions Excreted by kidneys Deacon et al.
DPP-IV Inhibitors What are the advantages of DPP-IV inhibitors compared with GLP-1 analogues?
Conclusion This means that multifactorial or “global” treatment to reduce the risk of vascular complications must now be the standard of care!
In phase 3 trials, the once-daily human glucagon-like peptide-1 analog liraglutide provided effective glycemic control with low rates of hypoglycemia, weight loss, and reduced systolic blood pressure (SBP) in patients with type 2 diabetes.
Patients attending Ulster Hospital who were prescribed liraglutide (June 2009a€“September 2010) and assessed both at baseline and first post-initiation visit were included in the analysis. IntroductionIn clinical trials of patients with type 2 diabetes, glucagon-like peptide-1 (GLP-1) receptor agonists have been shown to provide effective glycemic control when used in combination with oral antidiabetic drugs (OADs) [1]. Materials and MethodsThe authors assessed all patients who were prescribed liraglutide at Ulster Hospital from June 2009 to September 2010 and present data showing changes from baseline to the first hospital visit after initiation of liraglutide.
ResultsPatient Demographics and Baseline CharacteristicsA total of 193 patients were included in the audit, 50 of whom (25.9%) were prescribed liraglutide off-license with existing insulin regimens (off-license use of liraglutide was initiated on investigator request and it was their sole responsibility).
TolerabilityTwenty-three (11.9%) patients experienced GI effects, a known side effect of liraglutide, and these were mainly transient. AcknowledgmentsSponsorship for this study and article processing charges was funded by Novo Nordisk.


CM, data collection and editing of manuscript; RH, assistance with data collection and editing of manuscript. CM has been reimbursed by Novo Nordisk, Takeda and GlaxoSmithKline for attending several conferences, and has received speaker fees from Novo Nordisk, Eli Lilly and Bristol-Myers Squibb. This article does not contain any studies with human or animal subjects performed by any of the authors. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. If you interesting in "Present Therapies of Type 2 Diabetes Mellitus" powerpoint themes, you can download to use this powerpoint template for your own presentation template. Abdominal Obesity) PhysicalInactivity Aging Insulin Resistance Pro- Genetic Variation Atherogenic In CVD Risk Factor inflammatory Dyslipidemia Regulation State Pro- Elevated thrombotic Blood Pressure Hyperglycemia Modified from S. PPAR gamma Agonists do have the potential to prevent or delay the development of Type 2 Diabetes in high risk individuals.2.
Baseline values reflect the average baseline A across al treatments as estimated using this 1c model.RESULT (Study 135). Results of this trial are biased because they include only those patients who elected to continue on rosiglitazone plus metformin for the ful duration. Captopril and atenolol were equal y effective in reducing risk and were equal y safe in patients with diabetes. Low-grade Inflammation NASH Hypertension Prothrombotic Endothelial State Dyslipidemia Hyperglycemia Dysfunction O.
Through a retrospective clinical audit, the authors aimed to assess the clinical effectiveness of liraglutide, from initiation to first hospital visit, when prescribed at a center in Northern Ireland. However, data regarding the use of GLP-1 receptor agonists in clinical practice are scarce. In line with recommendations for initiating liraglutide and improving gastrointestinal (GI) tolerability, the starting dose of liraglutide was 0.6A mg daily. Among patients taking insulin in combination with liraglutide, 13 used basal insulin at baseline, 27 used basala€“bolus regimens, and 10 used a premixed insulin. Editorial assistance in the preparation of this manuscript was provided by Helen Stimpson and David Harvey of Watermeadow Medical. AP, data analyses and manuscript editing to ensure correct interpretation of statistical analyses.
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Based on the design of this study, patients may have received 4 mg or 8 mg Avandia in combination with glipizide. Here, the authors report data from the use of the once-daily human GLP-1 analog liraglutide in clinical practice.Liraglutide is a once-daily human GLP-1 analog with 97% amino acid sequence identity to native GLP-1 [2]. Limitations of the present study include its single-arm observational design, the absence of a fixed timeline for the first visit, and the fact that it was conducted at a single center. Doses of Avandia greater than 4 mg daily in combination with a sulfonylurea have not been approved.‡A at last observation in study.


In phase 3 trials, liraglutide has been found to provide glycemic control alongside potential beneficial effects on body weight, reductions in systolic blood pressure (SBP), and improved beta-cell function [3a€“9]. The primary endpoint assessed was change in glycated hemoglobin (HbA1c) from baseline to first clinic visit after the initiation of liraglutide. Furthermore, patients received concomitant medications that may have affected the measured outcomes, and these medications may have changed during the course of the study.In this study, the insulin dose did not need to be reduced in patients who were using liraglutide with insulin. The number of patients experiencing minor hypoglycemic events was low (5.7%) and no major events were reported.
Liraglutide treatment has also been found to be associated with a low risk of hypoglycemia, particularly when used without concomitant sulfonylurea treatment [3a€“9]. This observation is likely to be a reflection of the fact that initial glycemic control in these patients was poor. A clinical trial of the GLP-1 receptor agonist exenatide twice daily in combination with insulin also showed reductions in HbA1c [12], and another trial exploring the sequential addition to metformin of liraglutide and then insulin detemir also reported good glycemic control, sustained weight loss, and low rates of hypoglycemia [13].
Mulligan is the guarantor for this article, and takes responsibility for the integrity of the work as a whole.
The authors hypothesized that in a real-life clinical setting, despite the use of different background therapies, liraglutide treatment would result in comparable changes in HbA1c, body weight, and SBP to those observed in clinical trials.
Stata 10 (StataCorp, 2007) was used to calculate means (SD) by summary descriptive statistics after data manipulation [11]. Based on these data, in Europe, exenatide twice daily is licensed for use in combination with basal insulin, and insulin detemir can be added to existing liraglutide therapy [14, 15]. Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26A weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with type 2 diabetes (LEAD-1 SU). Liraglutide improved glycemic control, body weight, and SBP, indicating that liraglutide is effective in a real-life setting. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin in type 2 diabetes. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6).
Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Sequential intensification of metformin treatment in type 2 diabetes with liraglutide followed by randomized addition of basal insulin prompted by A1C targets.



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