PPG Is Acknowledged By 70% Of Diabetes Specialists As Being Equally Important To FPG For Achieving HbA1c Goals In Type 2 Diabetes Mellitus
A new survey commissioned by Sanofi Diabetes reveals that seven in 10 (70%) diabetes specialists believe that postprandial plasma glucose (PPG) is as important as fasting plasma glucose (FPG) in the management of Type 2 diabetes mellitus (T2DM) for achieving target glycated haemoglobin (HbA1c) levelsi. In addition, 80% of those surveyed suggest there is a need for new treatments that address elevated PPG concentrations, leading to optimal glycaemic controli. These survey findings are released as new data for Lyxumia® (lixisenatide) is announced by Sanofi at the Annual Meeting of the European Association for the Study of Diabetes (EASD) 2012.
Achieving optimal blood glucose control is the cornerstone of the management of T2DM as this reduces the likelihood of diabetes complications such as heart disease, stroke, retinopathy, neuropathy and nephropathy[ii]. There is established consensus on fasting plasma glucose (FPG) as a target for reducing a patient’s HbA1c. However, growing evidence supports the importance of also reducing PPG for achieving ideal HbA1c levels and reducing cardiovascular disease risk for certain groups of patientsii,[iii],[iv],[v].
In a recent study, a significant proportion (40%) of patients with T2DM treated with basal insulin and oral antidiabetic drug (OAD) therapy achieved FPG but not HbA1c targetsiv. This implies that PPG may be under-recognised and under-treated as a contributing factor to overall blood glucose control. As a result of this, these patients need additional treatments that control postprandial peaks, in addition to basal insulin, in order to achieve their HbA1c goal. The evidence suggests that whilst FPG is a key focus in the initial management of those with poor glycaemic control, PPG should also be targeted for optimal glycaemic control[vi].
This concept is supported by the International Diabetes Federation (IDF) Guideline for the Management of Postmeal Glucose, which outlines in detail the significant risk posed by postprandial hyperglycaemiaii.
This latest survey, conducted with over 300 diabetes specialists (100 endocrinologists, 100 diabetologists and 100 diabetes specialist nurses)i, was commissioned in light of the ongoing debate amongst healthcare professionals regarding the role of PPG (the term used to define plasma glucose concentrations after eating[vii]) in the overall management of T2DM.
Nearly all respondents (97%) stated that tighter overall glycaemic control is important in the management of T2DM, with 99% appreciating that it achieves better outcomes for patientsi. Three quarters (75%) of those surveyed suggest that monitoring of PPG levels should be introduced into diabetes clinicsi.
Dr Mike Baxter, Consultant Diabetologist and Endocrinologist at the Runnymede Hospital and Consultant Advisor at Sanofi Diabetes said: “The results of this survey support the growing body of evidence highlighting the importance of controlling PPG levels as a key part of the management of some patients with Type 2 diabetes, particularly those in whom intensive diabetic control has been highlighted as a priority in their individualised care plan.”
Six in 10 (60%) diabetes specialists surveyed state they are unaware of any guidelines relating to the monitoring of PPG as part of the management of T2DMi. The findings call for an improvement in the awareness of guidance relating to the monitoring of PPG as part of the overall management of the conditioni.
Professor David Owens, Emeritus Professor at Cardiff University, Institute of Molecular and Experimental Medicine, who was member of the IDF Guideline Development Group commented: “Whilst there is certainly a growing awareness of the importance of measuring PPG amongst healthcare professionals, it is clear that there needs to be more awareness and uptake of the recent IDF Guideline for the Management of Postmeal Glucose (2011) as well as the development of a UK specific version of the guideline. We also need to ensure that persons with diabetes are educated about PPG self-monitoring and recognise its importance as part of the routine management of their condition.”
The results of this survey coincide with positive new data on lixisenatide announced by Sanofi at the EASD Annual Meeting 2012. The study found that once-daily lixisenatide injected subcutaneously in the morning significantly delayed gastric emptying, with a significant impact on PPG and blood glucose levels throughout the day, contributing to overall glycaemic control[viii].
The 28-day, randomised, double-blind, placebo-controlled, parallel-group study in patients with T2DM (lixisenatide n=19; placebo n=22) demonstrated that a final dose of once-daily 20 μg lixisenatide in the morning (after titrating from 5-20 μg with 2.5 μg increments every 4 days), in addition to up to two oral anti-diabetic agents, had a significant delay on the rate of gastric emptying compared with placebo, which improved the blood glucose levels throughout the day8. At day 28, PPG was significantly reduced after a standardised breakfast (p<0.0001), after lunch (p=0.0004) and after dinner (p=0.0082) viii. No such relationship was found for placeboviii.
About the research
The survey was conducted by research agency Medefield and funded by Sanofi. The research surveyed 300 healthcare professionals specialising in diabetes. The sample was broken down in to 100 diabetes specialist nurses, 100 diabetologists and 100 endocrinologistsi. The survey questioned the diabetes specialists on their awareness of the role of PPG in the management of T2DM.
About Lyxumia® (lixisenatide)
Lixisenatide*, a glucagon-like peptide-1 agonist (GLP-1), is in development for the treatment of patients with Type 2 diabetes mellitus (T2DM)[ix]. Lixisenatide was in-licensed from Zealand Pharma A/S (Copenhagen, Denmark), www.zealandpharma.com. Lyxumia® is the intended trademark of lixisenatide. Lixisenatide is not currently approved or licensed anywhere in the world.
GLP-1 is a naturally-occurring peptide that is released within minutes of eating a meal. It is known to suppress glucagon secretion from pancreatic alpha cells and stimulate insulin secretion by pancreatic beta cells[x]. GLP-1 receptor agonists are in development as an add-on treatment for T2DM and their use is endorsed by the European Association for the Study of Diabetes, the American Diabetes Association, the American Association of Clinical Endocrinologists and the American College of Endocrinology[xi].
About glycated haemoglobin (HbA1c)
Until recently, the predominant focus of therapy in Type 2 diabetes mellitus (T2DM) has been on lowering HbA1c levels, with a strong emphasis on fasting plasma glucose (FPG). HbA1c occurs when glucose joins with haemoglobin in the red blood cell. When glucose sticks to the haemoglobin molecules it forms a glycated haemoglobin molecule, known as glycated HbA1c. The more glucose found in the blood the more glycated HbA1c will be present. By measuring glycated HbA1c, an average blood glucose reading can be returned due to the fact that red blood cells can survive for 8-12 weeks before being replaced in the circulation[xii]. HbA1c levels are often influenced by 2 factors – a patient’s fasting plasma glucose (FPG) and their postprandial glucose (PPG)[xiii].
About postprandial plasma glucose (PPG)
PPG is the term used to define plasma glucose concentrations after eatingviii. This number is highly variable and depends on what has been eaten. If a meal is eaten that is high in carbohydrate, blood sugars will go up quickly and come down rapidly. If a meal is high in protein and relatively low in carbohydrate, then blood sugars tend to rise more slowly and to a lower peak level, before gradually decreasing. This is especially important in T2DM which develops when the body does not produce enough insulin to maintain a normal blood glucose level, or when the body is unable to effectively use the insulin that is being produced[xiv].
A patient’s PPG profile is determined by carbohydrate absorption, insulin and glucagon secretion, and their coordinated effects on glucose metabolism in the liver and peripheral tissuesvii.
[i] Sanofi data on file
[ii] Guideline for the management of postmeal glucose. International Diabetes Federation, published 2007
[iii] Riddle M, Umpierrez G, DiGenio A. et al. Contributions of Basal and Postprandial Hyperglycemia Over a Wide Range of A1CLevels Before and After Treatment Intensification in Type 2 Diabetes. Diabetes Care, 2011; 34: 2508-2514
[iv] Colclough H., Piercy J., Benford M. Levels of FPG and HbA1c control and the relationship to BMI in T2D patients treated with basal insulin and OAD therapy. Abstract presented at ADA, June 2012
[v] Effects of Intensive Glucose Lowering in Type 2 Diabetes, The Action to Control Cardiovascular Risk in Diabetes Study Group (ACCORD). N Engl J. Med 2008, 358: 2545-2559
[vi] Baxter, M. The role of new basal insulin analogues in the initiation and optimisation of insulin therapy in type 2 diabetes. Acta Diabetol 2008;45:253-268
[vii] American Diabetes Association. Postprandial Blood Glucose. Diabetes Care. 24; 4 (2001)
[viii] Lorenz M., Pfeiffer, C., Steinsträßer, P. et al. Effects of lixisenatide once daily on gastric emptying and its relationship to postprandial glycaemia in Type 2 diabetes mellitus. Poster presented at EASD, October 2012
[ix] Christensen M, Knop F, Vilsbøll T et al. The GetGoal clinical trial program of lixisenatide, a once-daily GLP-1 receptor agonist. Expert Rev. Endocrinol. Metab. 6(4), 513–525 (2011)
[x] Pinkney J. et al. Selecting GLP-1 agonists in the management of type 2 diabetes: differential pharmacology and therapeutic benefits of liraglutide and exenatide. Therapeutics and Clinical Risk Management 2010; 6:401–411
[xi] Reid T. Choosing GLP-1 Receptor Agonists or DPP-4 Inhibitors: Weighing the Clinical Trial Evidence. Clinical Diabetes 2012; 30 (1): 3-12
[xii] Diabetes.co.uk. Guide to HbA1c. Access via: http://www.diabetes.co.uk/what-is-hba1c.html Last accessed: June 2012
[xiii] Sneider H, Sawtell PA, Ross L. HbA1c Levels Are Genetically Determined Even in Type 1 Diabetes. Access via: http://diabetes.diabetesjournals.org/content/50/12/2858.full.pdf Last accessed: June 2012
[xiv] Diabetes UK Guide to Type 2 diabetes http://www.diabetes.org.uk/Guide-to-diabetes/Type-2-diabetes/ Last accessed: July 2012