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      Efficacy and safety of dapagliflozin plus saxagliptin vs monotherapy as added to metformin in patients with type 2 diabetes : A meta-analysis

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          Abstract

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          Abstract

          Background:

          This study aim at evaluating the efficacy and safety of dapagliflozin plus saxagliptin vs monotherapy as added to metformin in patients with type 2 diabetes mellitus (T2DM).

          Method:

          PubMed, Cochrane library, Embase, CNKI and Wanfang databases were searched up to 31 December 2019. Randomized controlled trials (RCTs) applicable in dapagliflozin plus saxagliptin vs monotherapy as added to metformin in the treatment of T2DM were included. The outcomes included changes in HbA1c, FPG, body weight, SBP, DBP and adverse reactions. Fixed or random effects model were used to assess these outcomes.

          Results:

          In this study, 8 RCTs involved 7346 patients were included. Compared with dapagliflozin plus metformin(DM) group, patients treated with dapagliflozin plus saxagliptin add on to metformin(DSM) could significantly increase the adjusted mean change levels of HbA1c, FPG, SBP and DBP( P < .00001, SMD = −4.88, 95%CI = −6.93∼−2.83; P < .00001, SMD = −6.50, 95%CI = −8.55∼−4.45; P < .00001, SMD = −0.97, 95%CI = −1.15∼−0.78; P < .00001, SMD = −2.00, 95%CI = −2.20∼−1.80), but no major difference in body weight loss showed( P = .12, SMD = 0.92, 95%CI = −0.22∼2.06). Furthermore, DSM therapy displayed better effects than saxagliptin plus metformin(SM) in the adjusted mean change levels of HbA1c, FPG, body weight and SBP( P < .00001, SMD = −7.75, 95%CI = −8.84∼−6.66; P < .00001, SMD = −7.75, 95%CI = −8.84∼−6.66; P = .04, SMD = −3.40, 95%CI = −6.64∼−0.17; P = .04, SMD = −7.75, 95%CI = −8.84∼−6.66), whereas no obvious difference in lowering DBP( P = .18, SMD = −16.35, 95%CI = −40.12∼7.41). Additionally, compared with DM and SM groups, there were no remarkable difference in the incidence of nausea, influenza, headache, diarrhea, urinary tract infection and renal failure for patients taking DSM, but the incidence of genital infection and hypoglycemia were higher in DSM group.

          Conclusions:

          Patients taking the DSM therapy had better effects in reducing the level of HbA1c, FPG, body weight, SBP and DBP than the DM and SM therapy. However, patients treated with DSM therapy are more likely to have hypoglycemia and genital infection. Dapagliflozin plus saxagliptin may be a suitable therapy strategy for patients with T2DM inadequately controlled with metformin, and this will provide a clinical reference for the treatment of T2DM.

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          Most cited references30

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          Metformin: an old but still the best treatment for type 2 diabetes

          The management of T2DM requires aggressive treatment to achieve glycemic and cardiovascular risk factor goals. In this setting, metformin, an old and widely accepted first line agent, stands out not only for its antihyperglycemic properties but also for its effects beyond glycemic control such as improvements in endothelial dysfunction, hemostasis and oxidative stress, insulin resistance, lipid profiles, and fat redistribution. These properties may have contributed to the decrease of adverse cardiovascular outcomes otherwise not attributable to metformin’s mere antihyperglycemic effects. Several other classes of oral antidiabetic agents have been recently launched, introducing the need to evaluate the role of metformin as initial therapy and in combination with these newer drugs. There is increasing evidence from in vivo and in vitro studies supporting its anti-proliferative role in cancer and possibly a neuroprotective effect. Metformin’s negligible risk of hypoglycemia in monotherapy and few drug interactions of clinical relevance give this drug a high safety profile. The tolerability of metformin may be improved by using an appropiate dose titration, starting with low doses, so that side-effects can be minimized or by switching to an extended release form. We reviewed the role of metformin in the treatment of patients with type 2 diabetes and describe the additional benefits beyond its glycemic effect. We also discuss its potential role for a variety of insulin resistant and pre-diabetic states, obesity, metabolic abnormalities associated with HIV disease, gestational diabetes, cancer, and neuroprotection.
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            CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM - 2018 EXECUTIVE SUMMARY.

            A1C = hemoglobin A1C; AACE = American Association of Clinical Endocrinologists; ACCORD = Action to Control Cardiovascular Risk in Diabetes; ACCORD BP = Action to Control Cardiovascular Risk in Diabetes Blood Pressure; ACEI = angiotensin-converting enzyme inhibitor; ADVANCE = Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation; AGI = alpha-glucosidase inhibitor; apo B = apolipoprotein B; ASCVD = atherosclerotic cardiovascular disease; BAS = bile acid sequestrant; BCR-QR = bromocriptine quick release; BMI = body mass index; BP = blood pressure; CCB = calcium channel blocker; CHD = coronary heart disease; CKD = chronic kidney disease; CVD = cardiovascular disease; DASH = Dietary Approaches to Stop Hypertension; DPP4 = dipeptidyl peptidase 4; eGFR = estimated glomerular filtration rate; ER = extended release; FDA = Food and Drug Administration; GLP1 = glucagon-like peptide 1; HDL-C = high-density lipoprotein cholesterol; IMPROVE-IT = Improved Reduction of Outcomes: Vytorin Efficacy International Trial; LDL-C = low-density lipoprotein cholesterol; LDL-P = low-density lipoprotein particle; Look AHEAD = Look Action for Health in Diabetes; NPH = neutral protamine Hagedorn; OSA = obstructive sleep apnea; RCT = randomized controlled trial; SU = sulfonylurea; SGLT2 = sodium glucose cotransporter-2; SMBG = self-monitoring of blood glucose; T2D = type 2 diabetes; TZD = thiazolidinedione; VADT = Veterans Affairs Diabetes Trial.
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              Urinary tract and genital infections in patients with type 2 diabetes treated with sodium-glucose co-transporter 2 inhibitors: A meta-analysis of randomized controlled trials.

              To evaluate the effects of different sodium-glucose co-transporter 2 (SGLT2) inhibitors on the risk of urinary tract infections (UTIs) and genital infections in patients with type 2 diabetes mellitus (T2DM).
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                24 July 2020
                24 July 2020
                : 99
                : 30
                : e21409
                Affiliations
                [a ]Department of Clinical Laboratory
                [b ]Department of Nursing
                [c ]Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
                Author notes
                []Correspondence: Mingxing Li, Miaofa Ying, Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, No. 3 Qingchun east road, Jianggan District, Hangzhou, China (e-mail: mxlsrrsh18zju.edu.cn, yfmsrrsh17@ 123456163.com ).
                Author information
                http://orcid.org/0000-0002-9730-1357
                Article
                MD-D-20-02187 21409
                10.1097/MD.0000000000021409
                7386974
                d94e220e-5107-4be5-9e16-eb6475f05425
                Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

                History
                : 10 March 2020
                : 15 June 2020
                : 22 June 2020
                Funding
                Funded by: zhejiang provincial natural science foundation
                Award ID: LYY19H310010
                Award Recipient : Mingxing Li
                Categories
                4300
                Research Article
                Systematic Review and Meta-Analysis
                Custom metadata
                TRUE

                type 2 diabetes mellitus,dapagliflozin,saxagliptin,randomized controlled trials,meta-analysis

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