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      Modern-Day Management of the Dysglycemic Continuum: An Expert Viewpoint from the Arabian Gulf

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          Abstract

          Prediabetes is the first stage of a continuum that extends through the diagnosis of clinical type 2 diabetes towards long-standing diabetes with multiple comorbidities. The diagnosis of prediabetes provides an opportunity to interrupt the diabetes continuum at an early stage to ensure long-term optimization of clinical outcomes. All people with prediabetes should receive intervention to improve their lifestyles (quality of diet and level of physical activity), as this has been proven beyond doubt to reduce substantially the risk of conversion to diabetes. Additionally, a large base of clinical evidence supports the use of metformin in preventing or delaying the transition from prediabetes to clinical type 2 diabetes, for some people with prediabetes. For many years, guidelines for the management of type 2 diabetes focused on lowering blood glucose, with metformin prescribed first for those without contraindications. More recently, guidelines have shifted towards prevention of diabetes complications as the primary goal, with increased use of GLP-1 receptor agonists (or multi-agonist incretin peptides) or SGLT-2 inhibitors for patients with existing atherosclerotic cardiovascular disease, heart failure or chronic kidney disease. Access to these medications often remains challenging. Metformin remains a suitable option for initial pharmacologic intervention to manage glycemia for many people with prediabetes or type 2 diabetes along with other therapy to maintain control of blood glucose or to address specific comorbidities as the patient progresses along the diabetes continuum.

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          Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.

          Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors--elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle--are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes. We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The mean age of the participants was 51 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 34.0; 68 percent were women, and 45 percent were members of minority groups. The average follow-up was 2.8 years. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. The lifestyle intervention reduced the incidence by 58 percent (95 percent confidence interval, 48 to 66 percent) and metformin by 31 percent (95 percent confidence interval, 17 to 43 percent), as compared with placebo; the lifestyle intervention was significantly more effective than metformin. To prevent one case of diabetes during a period of three years, 6.9 persons would have to participate in the lifestyle-intervention program, and 13.9 would have to receive metformin. Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.
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            2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD

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              10-year follow-up of intensive glucose control in type 2 diabetes.

              During the United Kingdom Prospective Diabetes Study (UKPDS), patients with type 2 diabetes mellitus who received intensive glucose therapy had a lower risk of microvascular complications than did those receiving conventional dietary therapy. We conducted post-trial monitoring to determine whether this improved glucose control persisted and whether such therapy had a long-term effect on macrovascular outcomes. Of 5102 patients with newly diagnosed type 2 diabetes, 4209 were randomly assigned to receive either conventional therapy (dietary restriction) or intensive therapy (either sulfonylurea or insulin or, in overweight patients, metformin) for glucose control. In post-trial monitoring, 3277 patients were asked to attend annual UKPDS clinics for 5 years, but no attempts were made to maintain their previously assigned therapies. Annual questionnaires were used to follow patients who were unable to attend the clinics, and all patients in years 6 to 10 were assessed through questionnaires. We examined seven prespecified aggregate clinical outcomes from the UKPDS on an intention-to-treat basis, according to previous randomization categories. Between-group differences in glycated hemoglobin levels were lost after the first year. In the sulfonylurea-insulin group, relative reductions in risk persisted at 10 years for any diabetes-related end point (9%, P=0.04) and microvascular disease (24%, P=0.001), and risk reductions for myocardial infarction (15%, P=0.01) and death from any cause (13%, P=0.007) emerged over time, as more events occurred. In the metformin group, significant risk reductions persisted for any diabetes-related end point (21%, P=0.01), myocardial infarction (33%, P=0.005), and death from any cause (27%, P=0.002). Despite an early loss of glycemic differences, a continued reduction in microvascular risk and emergent risk reductions for myocardial infarction and death from any cause were observed during 10 years of post-trial follow-up. A continued benefit after metformin therapy was evident among overweight patients. (UKPDS 80; Current Controlled Trials number, ISRCTN75451837.) 2008 Massachusetts Medical Society
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                Author and article information

                Journal
                Diabetes Metab Syndr Obes
                Diabetes Metab Syndr Obes
                dmso
                Diabetes, Metabolic Syndrome and Obesity
                Dove
                1178-7007
                17 December 2024
                2024
                : 17
                : 4791-4802
                Affiliations
                [1 ]Division of Endocrinology, Jaber Al-Ahmad Hospital , Kuwait City, Kuwait
                [2 ]Endocrine Department, Dubai Hospital, Dubai Academic Health Corporation (DAHC) , Dubai, United Arab Emirates
                [3 ]Department of Internal Medicine, College of Medicine and Health Sciences, The United Arab Emirates University , Al-Ain, United Arab Emirates
                [4 ]Department of Medicine, Sultan Qaboos University Hospital , Muscat, Oman
                [5 ]Clinical Research Unit, Dasman Diabetes Institute , Dasman, Kuwait
                [6 ]Internal Medicine Department, Royal College of Surgeons in Ireland-Medical University of Bahrain , Adliya, Kingdom of Bahrain
                [7 ]Endocrine Section, Department of Medicine, Hamad Medical Corporation , Doha, Qatar
                [8 ]Internal Medicine, Sana’a University Faculty of Medicine , Sanaa, Yemen
                [9 ]Department of Endocrinology and Diabetes, Dubai Hospital, Dubai Academic Health Corporation (DAHC) , Dubai, United Arab Emirates
                [10 ]Department of Endocrinology, Hamad Medical Corporation , Doha, Qatar
                [11 ]Medical Affairs, Merck Serono Middle East FZ-LLC , Dubai, United Arab Emirates
                [12 ]Global Research & Development Medical – MU CM&E, Merck Healthcare KGaA , Darmstadt, Germany
                Author notes
                Correspondence: Thamer Alessa, Division of Endocrinology, Jaber Al-Ahmad hospital, South Surra, Ministries Area , Kuwait City, 13060, Kuwait, Email talessa@moh.gov.kw
                Author information
                http://orcid.org/0000-0003-4658-9562
                http://orcid.org/0000-0003-2477-0408
                http://orcid.org/0000-0001-5006-4369
                http://orcid.org/0000-0001-8470-6286
                http://orcid.org/0000-0002-5971-3094
                http://orcid.org/0000-0002-8374-4026
                Article
                491591
                10.2147/DMSO.S491591
                11662629
                39712240
                b3f8e454-e136-4677-ba51-b7cf1f32be07
                © 2024 Alessa et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 15 August 2024
                : 26 October 2024
                Page count
                Figures: 2, Tables: 1, References: 102, Pages: 12
                Funding
                Funded by: Merck Serono Middle East FZ-Ltd. also funded editorial assistance (see Acknowledgements) and the article processing charge. No other funding applied;
                The consensus meeting that gave rise to this article was funded by Merck Serono Middle East FZ-Ltd, an affiliate of Merck KGaA, Darmstadt, Germany. This company did not influence the treatment recommendations made here, which are the views of the authors. Merck Serono Middle East FZ-Ltd. also funded editorial assistance (see Acknowledgements) and the article processing charge. No other funding applied.
                Categories
                Review

                Endocrinology & Diabetes
                type 2 diabetes,prediabetes,diabetes continuum,metformin,antidiabetic therapy,diabetes complications

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