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      Evidence-Based Consensus on Positioning of SGLT2i in Type 2 Diabetes Mellitus in Indians

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          Abstract

          The current diabetes management strategies not only aim at controlling glycaemic parameters but also necessitate continuous medical care along with multifactorial risk reduction through a comprehensive management concept. The sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a group of evolving antidiabetic agents that have the potential to play a pivotal role in the comprehensive management of patients with diabetes due to their diverse beneficial effects. SGLT2i provide moderate glycaemic control, considerable body weight and blood pressure reduction, and thus have the ability to lower the risk of macrovascular and microvascular complications. Some of the unique characteristics associated with SGLT2i, such as reduction in body weight (more visceral fat mass loss than subcutaneous fat loss), reduction in insulin resistance and improvement in β-cell function, as measured by homeostatic model assessment-β (HOMA-β) could be potentially beneficial and help in overcoming some of the challenges faced by Indian patients with diabetes. In addition, a patient-centric approach with individualised treatment during SGLT2i therapy is inevitable in order to reduce diabetic complications and improve quality of life. Despite their broad benefits profile, the risk of genital tract infections, volume depletion, amputations and diabetic ketoacidosis associated with SGLT2i should be carefully monitored. In this compendium, we systematically reviewed the literature from Medline, Cochrane Library, and other relevant databases and attempted to provide evidence-based recommendations for the positioning of SGLT2i in the management of diabetes in the Indian population.

          Funding : AstraZeneca Pharma India Limited.

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          Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial.

          The effectiveness of intentional weight loss in reducing cardiovascular disease (CVD) events in type 2 diabetes is unknown. This report describes 1-year changes in CVD risk factors in a trial designed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events. This study consisted of a multicentered, randomized, controlled trial of 5,145 individuals with type 2 diabetes, aged 45-74 years, with BMI >25 kg/m2 (>27 kg/m2 if taking insulin). An intensive lifestyle intervention (ILI) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared with a diabetes support and education (DSE) condition. Participants assigned to ILI lost an average 8.6% of their initial weight vs. 0.7% in DSE group (P < 0.001). Mean fitness increased in ILI by 20.9 vs. 5.8% in DSE (P < 0.001). A greater proportion of ILI participants had reductions in diabetes, hypertension, and lipid-lowering medicines. Mean A1C dropped from 7.3 to 6.6% in ILI (P < 0.001) vs. from 7.3 to 7.2% in DSE. Systolic and diastolic pressure, triglycerides, HDL cholesterol, and urine albumin-to-creatinine ratio improved significantly more in ILI than DSE participants (all P < 0.01). At 1 year, ILI resulted in clinically significant weight loss in people with type 2 diabetes. This was associated with improved diabetes control and CVD risk factors and reduced medicine use in ILI versus DSE. Continued intervention and follow-up will determine whether these changes are maintained and will reduce CVD risk.
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            Type 2 diabetes in East Asians: similarities and differences with populations in Europe and the United States

            There is an epidemic of diabetes in Asia. Type 2 diabetes develops in East Asian patients at a lower mean body mass index (BMI) compared with those of European descent. At any given BMI, East Asians have a greater amount of body fat and a tendency to visceral adiposity. In Asian patients, diabetes develops at a younger age and is characterized by early β cell dysfunction in the setting of insulin resistance, with many requiring early insulin treatment. The increasing proportion of young-onset and childhood type 2 diabetes is posing a particular threat, with these patients being at increased risk of developing diabetic complications. East Asian patients with type 2 diabetes have a higher risk of developing renal complications than Europeans and, with regard to cardiovascular complications, a predisposition for developing strokes. In addition to cardiovascular–renal disease, cancer is emerging as the other main cause of mortality. While more research is needed to explain these interethnic differences, urgent and concerted actions are needed to raise awareness, facilitate early diagnosis, and encourage preventive strategies to combat these growing disease burdens.
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              Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.

              Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion, and weight loss is a consistent associated finding. Our objectives were to confirm weight loss with dapagliflozin and establish through body composition measurements whether weight loss is accounted for by changes in fat or fluid components. This was a 24-wk, international, multicenter, randomized, parallel-group, double-blind, placebo-controlled study with ongoing 78-wk site- and patient-blinded extension period at 40 sites in five countries. Included were 182 patients with T2DM (mean values: women 63.3 and men 58.6 yr of age; hemoglobin A1c 7.17%, body mass index 31.9 kg/m2, and body weight 91.5 kg) inadequately controlled on metformin. Dapagliflozin 10 mg/d or placebo was added to open-label metformin for 24 wk. Primary endpoint was total body weight (TBW) change from baseline at wk 24. Key secondary endpoints were waist circumference and dual-energy x-ray absorptiometry total-body fat mass (FM) changes from baseline at wk 24, and patient proportion achieving body weight reduction of at least 5% at wk 24. In a subset of patients, magnetic resonance assessment of visceral adipose tissue (VAT) and sc adipose tissue (SAT) volume and hepatic lipid content were also evaluated. At wk 24, placebo-corrected changes with dapagliflozin were as follows: TBW, -2.08 kg [95% confidence interval (CI)=-2.84 to -1.31; P<0.0001]; waist circumference, -1.52 cm (95% CI=-2.74 to -0.31; P=0.0143); FM, -1.48 kg (95% CI=-2.22 to -0.74; P=0.0001); proportion of patients achieving weight reduction of at least 5%, +26.2% (95% CI=15.5 to 36.7; P<0.0001); VAT, -258.4 cm3 (95% CI=-448.1 to -68.6; nominal P=0.0084); SAT, -184.9 cm3 (95% CI=-359.7 to -10.1; nominal P=0.0385). In the dapagliflozin vs. placebo groups, respectively, serious adverse events were reported in 6.6 vs. 1.1%; events suggestive of vulvovaginitis, balanitis, and related genital infection in 3.3 vs. 0%; and lower urinary tract infections in 6.6 vs. 2.2%. Dapagliflozin reduces TBW, predominantly by reducing FM, VAT and SAT in T2DM inadequately controlled with metformin.
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                Author and article information

                Contributors
                singhawadheshkumar2018@gmail.com
                Journal
                Diabetes Ther
                Diabetes Ther
                Diabetes Therapy
                Springer Healthcare (Cheshire )
                1869-6953
                1869-6961
                31 January 2019
                31 January 2019
                April 2019
                : 10
                : 2
                : 393-428
                Affiliations
                [1 ]GD Hospital and Diabetes Institute, Kolkata, West Bengal India
                [2 ]Chellaram Diabetes Institute, Pune, Maharashtra India
                [3 ]Advanced Centre for Diabetes and Endocrine Care, Srinagar, Jammu and Kashmir India
                [4 ]GRID grid.477262.2, Diabetes Care and Research Centre, ; Patna, Bihar India
                [5 ]ISNI 0000 0004 1767 8424, GRID grid.415098.1, Pondicherry Institute of Medical Sciences, ; Pondicherry, India
                [6 ]GRID grid.477253.0, Diacare-Diabetes Care & Hormone Clinic, ; Ahmedabad, Gujarat India
                [7 ]ISNI 0000 0004 1799 7281, GRID grid.459320.9, AMRI Hospitals, ; Kolkata, West Bengal India
                [8 ]Fortis and Peerless Hospitals, Kolkata, West Bengal India
                [9 ]Talwalkar Diabetes Clinic, Mumbai, Maharashtra India
                [10 ]GRID grid.477599.1, Nightingale Hospital, ; Kolkata, West Bengal India
                [11 ]ISNI 0000 0004 1803 0590, GRID grid.470178.d, Bharti Hospital & B.R.I.D.E, ; Karnal, Haryana India
                [12 ]ISNI 0000 0004 1766 8592, GRID grid.415923.8, Lilavati Hospital and Research Centre, ; Mumbai, Maharashtra India
                [13 ]Galaxy Speciality Centre, Jaipur, Rajasthan India
                [14 ]Clinical Endocrinology Education and Research (ACEER), Chennai, Tamil Nadu India
                [15 ]ISNI 0000 0004 1805 2183, GRID grid.410867.c, Dr Mohan’s Diabetes Specialities Centre and Madras Diabetes Research Foundation, ; Chennai, Tamil Nadu India
                Article
                562
                10.1007/s13300-019-0562-1
                6437257
                30706366
                43492817-3bd1-4002-a90a-3a9d5d6b22c6
                © The Author(s) 2019
                History
                : 23 October 2018
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                Endocrinology & Diabetes
                dapagliflozin,glycaemic efficacy,indian population,sglt2i,type 2 diabetes
                Endocrinology & Diabetes
                dapagliflozin, glycaemic efficacy, indian population, sglt2i, type 2 diabetes

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