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      Optimising the medical management of hyperglycaemia in type 2 diabetes in the Middle East: pivotal role of metformin

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          Abstract

          Aims:

          Increases in the prevalence of type 2 diabetes will likely be greater in the Middle East and other developing countries than in most other regions during the coming two decades, placing a heavy burden on regional healthcare resources.

          Methodology:

          Medline search, examination of data from major epidemiological studies in the Middle Eastern countries.

          Results:

          The aetiology and pathophysiology of diabetes appears comparable in Middle Eastern and other populations. Lifestyle intervention is key to the management of diabetes in all type 2 diabetes patients, who should be encouraged strongly to diet and exercise. The options for pharmacologic therapy in the management of diabetes have increased recently, particularly the number of potential antidiabetic combinations. Metformin appears to be used less frequently to initiate antidiabetic therapy in the Middle East than in other countries. Available clinical evidence, supported by current guidelines, strongly favours the initiation of antidiabetic therapy with metformin in Middle Eastern type 2 diabetes patients, where no contraindications exist. This is due to its equivalent or greater efficacy relative to other oral antidiabetic treatments, its proven tolerability and safety profiles, its weight neutrality, the lack of clinically significant hypoglycaemia, the demonstration of cardiovascular protection for metformin relative to diet in the UK Prospective Diabetes Study and in observational studies, and its low cost. Additional treatments should be added to metformin and lifestyle intervention as diabetes progresses, until patients are receiving an intensive insulin regimen with or without additional oral agents.

          Conclusions:

          The current evidence base strongly favours the initiation of antidiabetic therapy with metformin, where no contraindications exist. However, metformin may be under-prescribed in the Middle East.

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          Most cited references60

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          Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial.

          Laser treatment for diabetic retinopathy is often associated with visual field reduction and other ocular side-effects. Our aim was to assess whether long-term lipid-lowering therapy with fenofibrate could reduce the progression of retinopathy and the need for laser treatment in patients with type 2 diabetes mellitus. The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was a multinational randomised trial of 9795 patients aged 50-75 years with type 2 diabetes mellitus. Eligible patients were randomly assigned to receive fenofibrate 200 mg/day (n=4895) or matching placebo (n=4900). At each clinic visit, information concerning laser treatment for diabetic retinopathy-a prespecified tertiary endpoint of the main study-was gathered. Adjudication by ophthalmologists masked to treatment allocation defined instances of laser treatment for macular oedema, proliferative retinopathy, or other eye conditions. In a substudy of 1012 patients, standardised retinal photography was done and photographs graded with Early Treatment Diabetic Retinopathy Study (ETDRS) criteria to determine the cumulative incidence of diabetic retinopathy and its component lesions. Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN64783481. Laser treatment was needed more frequently in participants with poorer glycaemic or blood pressure control than in those with good control of these factors, and in those with a greater burden of clinical microvascular disease, but the need for such treatment was not affected by plasma lipid concentrations. The requirement for first laser treatment for all retinopathy was significantly lower in the fenofibrate group than in the placebo group (164 [3.4%] patients on fenofibrate vs 238 [4.9%] on placebo; hazard ratio [HR] 0.69, 95% CI 0.56-0.84; p=0.0002; absolute risk reduction 1.5% [0.7-2.3]). In the ophthalmology substudy, the primary endpoint of 2-step progression of retinopathy grade did not differ significantly between the two groups overall (46 [9.6%] patients on fenofibrate vs 57 [12.3%] on placebo; p=0.19) or in the subset of patients without pre-existing retinopathy (43 [11.4%] vs 43 [11.7%]; p=0.87). By contrast, in patients with pre-existing retinopathy, significantly fewer patients on fenofibrate had a 2-step progression than did those on placebo (three [3.1%] patients vs 14 [14.6%]; p=0.004). An exploratory composite endpoint of 2-step progression of retinopathy grade, macular oedema, or laser treatments was significantly lower in the fenofibrate group than in the placebo group (HR 0.66, 95% CI 0.47-0.94; p=0.022). Treatment with fenofibrate in individuals with type 2 diabetes mellitus reduces the need for laser treatment for diabetic retinopathy, although the mechanism of this effect does not seem to be related to plasma concentrations of lipids.
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            U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group.

            The objective of the U.K. Prospective Diabetes Study is to determine whether improved blood glucose control in type II diabetes will prevent the complications of diabetes and whether any specific therapy is advantageous or disadvantageous. The study will report in 1998, when the median duration from randomization will be 11 years. This report is on the efficacy of therapy over 6 years of follow-up and the overall incidence of diabetic complications. Subjects comprised 4,209 newly diagnosed type II diabetic patients who after 3 months' diet were asymptomatic and had fasting plasma glucose (FPG) 6.0-15.0 mmol/l. The study consists of a randomized controlled trial with two main comparisons: 1) 3,867 patients with 1,138 allocated to conventional therapy, primarily with diet, and 2,729 allocated to intensive therapy with additional sulfonylurea or insulin, which increase insulin supply, aiming for FPG < 6 mmol/l; and 2) 753 obese patients with 411 allocated to conventional therapy and 342 allocated to intensive therapy with metformin, which enhances insulin sensitivity. In the first comparison, in 2,287 subjects studied for 6 years, intensive therapy with sulfonylurea and insulin similarly improved glucose control compared with conventional therapy, with median FPG at 1 year of 6.8 and 8.2 mmol/l, respectively (P < 0.0001). and median HbA1c of 6.1 and 6.8%, respectively (P < 0.0001). During the next 5 years, the FPG increased progressively on all therapies (P < 0.0001) with medians at 6 years in the conventional and intensive groups, FPG 9.5 and 7.8 mmol/l, and HbA1c 8.0 and 7.1%, respectively. The glycemic deterioration was associated with progressive loss of beta-cell function. In the second comparison, in 548 obese subjects studied for 6 years, metformin improved glucose control similarly to intensive therapy with sulfonylurea or insulin. Metformin did not increase body weight or increase the incidence of hypoglycemia to the same extent as therapy with sulfonylurea or insulin. A high incidence of clinical complications occurred by 6-year follow-up. Of all subjects, 18.0% had suffered one or more diabetes-related clinical endpoints, with 12.1% having a macrovascular and 5.7% a microvascular endpoint. Sulfonylurea, metformin, and insulin therapies were similarly effective in improving glucose control compared with a policy of diet therapy. The study is examining whether the continued improved glucose control, obtained by intensive therapy compared with conventional therapy (median over 6 years HbA1c 6.6% compared with 7.4%), will be clinically advantageous in maintaining health.
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              Diabetes mellitus in Saudi Arabia.

              Diabetes mellitus (DM) is a major public health problem worldwide, and it is a known risk factor for coronary artery disease (CAD). New recommendations for the diagnosis of diabetes have changed the epidemiology of DM. Therefore, we designed this study with the objective to determine the prevalence of DM among Saudis of both sexes, between the ages of 30-70-years in rural as well as urban communities. This work is part of a major national project: Coronary Artery Disease in Saudis study (CADISS) that is designed to look at CAD and its risk factors in Saudi population. This study is a community-based national epidemiological health survey, conducted by examining Saudi subjects in the age group of 30-70-years of selected households over a 5-year period between 1995 and 2000. Data were obtained from history, fasting plasma glucose levels, and body mass index. The data were analyzed to classify individuals as diabetic, impaired fasting glucose and normal, using 1997 American Diabetes Association (ADA) criteria, which was adopted by the World Health Organization (WHO) in 1998, to provide prevalence of DM in the Kingdom of Saudi Arabia (KSA). A total of 17232 Saudi subjects were selected in the study, and 16917 participated (98.2% response rate). Four thousand and four subjects (23.7%), out of 16917 were diagnosed to have DM. Thus, the overall prevalence of DM obtained from this study is 23.7% in KSA. The prevalence in males and females were 26.2% and 21.5% (p<0.00001). The calculated age-adjusted prevalence for Saudi population for the year 2000 is 21.9%. Diabetes mellitus was more prevalent among Saudis living in urban areas of 25.5% compared to rural Saudis of 19.5% (p<0.00001). Despite the readily available access to healthcare facilities in KSA, a large number of diabetics 1116 (27.9%) were unaware of having DM. The overall prevalence of DM in adults in KSA is 23.7%. A national prevention program at community level targeting high risk groups should be implemented sooner to prevent DM. We further recommend a longitudinal study to demonstrate the importance of modifying risk factors for the development of DM and reducing its prevalence in KSA.
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                Author and article information

                Journal
                Int J Clin Pract
                ijcp
                International Journal of Clinical Practice
                Blackwell Publishing Ltd
                1368-5031
                1742-1241
                January 2009
                : 64
                : 2
                : 149-159
                Affiliations
                [1 ]simpleKing Khalid University Hospital, King Saud University Riyadh, Saudi Arabia
                [2 ]simpleDasman Center for Research and Treatment of Diabetes Dasman, Kuwait
                [3 ]simpleAlexandria University Alexandria, Egypt
                [4 ]simpleAmerican University of Beirut Beirut, Lebanon
                [5 ]simpleJoslin Diabetes Center Dubai, United Arab Emirates
                [6 ]simpleMutah University Mutah, Karak, Jordan
                [7 ]simpleAl Hada Armed Forces Hospital Taif, Saudi Arabia
                [8 ]simpleImperial College London, UK
                Author notes
                Correspondence to: Dr Mohamed Al-Maatouq, Department of Medicine (38), College of Medicine & King Khalid University Hospital, King Saud University, P O Box 2925, Riyadh 11461, Saudi Arabia Tel.: + 966 1 4671497 Fax: + 966 1 4671494 Email: mmaatouq@ 123456ksu.edu.sa

                Disclosures The recommendations given above arose from a meeting of an expert panel of physicians from Middle-Eastern countries supported by an educational grant from Merck Serono, and authors received an honorarium for their contributions. Dr SH Assaad is a Principal Investigator for a research project supported by Merck Serono.

                Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://www3.interscience.wiley.com/authorresources/onlineopen.html

                Article
                10.1111/j.1742-1241.2009.02235.x
                2936120
                20089006
                1fcb2625-7448-40eb-8bdb-939e75cd7c09
                © 2009 Blackwell Publishing Ltd

                Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

                History
                : June 2009
                : September 2009
                Categories
                Consensus

                Medicine
                Medicine

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