PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33235419-7 2020 Results: After the six month follow-up, there was a significant decrease in the QT interval in patients who were using SGLT2 inhibitors as an add-on therapy to metformin compared to other glucose-lowering agents (373.4 +- 9.9 ms vs. 385.4 +- 12.5 ms, 382.9 +- 11.2 ms; p < 0.001 respectively). Metformin 160-169 solute carrier family 5 member 2 Homo sapiens 119-124 33973870-0 2021 The different hypoglycemic effects between East Asian and non-Asian type 2 diabetes patients when treated with SGLT-2 inhibitors as an add-on treatment for metformin: a systematic review and meta-analysis of randomized controlled trials. Metformin 156-165 solute carrier family 5 member 2 Homo sapiens 111-117 33973870-1 2021 AIMS: To investigate the efficacy and safety of SGLT-2 inhibitors as an add-on treatment for metformin between Asian and non-Asian T2DM. Metformin 93-102 solute carrier family 5 member 2 Homo sapiens 48-54 33973870-10 2021 CONCLUSION: SGLT-2 inhibitors as an add-on treatment for metformin are more efficacious in East Asian T2DM patients than in non-Asian T2DM patients without an additional risk of severe adverse events. Metformin 57-66 solute carrier family 5 member 2 Homo sapiens 12-18 33235419-9 2020 Conclusions: Our data showed that using SGLT2 inhibitors as an add-on therapy to metformin favorably alters ventricular repolarization indices in patients with type 2 diabetes mellitus. Metformin 81-90 solute carrier family 5 member 2 Homo sapiens 40-45 34180939-2 2021 Objective: To evaluate the comparative effectiveness of SGLT2 inhibitors and sulfonylureas associated with the risk of all-cause mortality among patients with type 2 diabetes using metformin. Metformin 181-190 solute carrier family 5 member 2 Homo sapiens 56-61 34866061-4 2021 This case illustrates the in vivo effect of an SGLT2 inhibitor in a 30-year-old woman with MODY3 with poor glycaemic control despite the treatment with supramaximal doses of sulfonylurea and metformin. Metformin 191-200 solute carrier family 5 member 2 Homo sapiens 47-52 34247911-1 2021 AIMS: This study aimed to compare cardiovascular benefits associated with the use of GLP-1RA versus SGLT2i as add-on therapies to metformin among adults with type 2 diabetes (T2D) with and without a history of cardiovascular complications, using real-world data. Metformin 130-139 solute carrier family 5 member 2 Homo sapiens 100-105 34247911-2 2021 METHODS: Using data from the IBM MarketScan Commercial Claims Databases, metformin users above 18years with T2D who initiated GLP-1RA or SGLT2i were identified. Metformin 75-84 solute carrier family 5 member 2 Homo sapiens 139-144 34180939-14 2021 In additional per-protocol analyses, continued use of SGLT2 inhibitors with metformin was associated with a reduced risk of death compared with SGLT2 inhibitor treatment without metformin (HR, 0.70; 95% CI, 0.50-0.97; event rate difference, -7.62; 95% CI, -17.12 to -0.48 deaths per 1000 person-years). Metformin 76-85 solute carrier family 5 member 2 Homo sapiens 54-59 34180939-15 2021 Conclusions and Relevance: In this comparative effectiveness study analyzing data from the US Department of Veterans Affairs, among patients with type 2 diabetes receiving metformin therapy, SGLT2 inhibitor treatment was associated with a reduced risk of all-cause mortality compared with sulfonylureas. Metformin 172-181 solute carrier family 5 member 2 Homo sapiens 191-196 35212193-11 2022 Metformin was the most commonly used antidiabetic medication, followed by insulin, sodium-glucose transport protein 2 (SGLT2) inhibitors, and sulfonylurea. Metformin 0-9 solute carrier family 5 member 2 Homo sapiens 119-124 34163481-6 2021 In addition, the combination of metformin with other drugs that improve the function of macrophages (such as SGLT2 inhibitors, statins and IL-1beta inhibitors/monoclonal antibodies) may further enhance the pleiotropic therapeutic potential of metformin in conditions such as atherosclerosis, obesity, cancer, dementia and aging. Metformin 32-41 solute carrier family 5 member 2 Homo sapiens 109-114 34163481-6 2021 In addition, the combination of metformin with other drugs that improve the function of macrophages (such as SGLT2 inhibitors, statins and IL-1beta inhibitors/monoclonal antibodies) may further enhance the pleiotropic therapeutic potential of metformin in conditions such as atherosclerosis, obesity, cancer, dementia and aging. Metformin 243-252 solute carrier family 5 member 2 Homo sapiens 109-114 34440108-0 2021 Metformin Therapy Effects on the Expression of Sodium-Glucose Cotransporter 2, Leptin, and SIRT6 Levels in Pericoronary Fat Excised from Pre-Diabetic Patients with Acute Myocardial Infarction. Metformin 0-9 solute carrier family 5 member 2 Homo sapiens 47-77 34440108-11 2021 PDM never-metformin-users showed higher SGLT2 and leptin levels in pericoronary fat than current-metformin-users (p < 0.05). Metformin 10-19 solute carrier family 5 member 2 Homo sapiens 40-45 34440108-12 2021 CONCLUSIONS: metformin therapy might ameliorate cardiovascular outcomes by reducing inflammatory parameters, SGLT2, and leptin levels, and finally improving SIRT6 levels in AMI-PDM patients treated with CABG. Metformin 13-22 solute carrier family 5 member 2 Homo sapiens 109-114 35120085-3 2022 Many glucose-lowering treatment options are available, but glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are recommended in recent guidelines as the preferred add-on therapy to metformin to improve glycemic control. Metformin 239-248 solute carrier family 5 member 2 Homo sapiens 148-154 35005849-8 2022 SGLT-2 inhibitors were associated with a higher risk of genital infections than DPP-4 inhibitors (HR: 2.39, 95% CI: 2.07-2.76), SU (HR: 3.23, 95% CI: 2.73-3.81), and TZD (HR: 3.23, 95% CI: 2.35-4.44), as an add-on therapy to metformin. Metformin 225-234 solute carrier family 5 member 2 Homo sapiens 0-6 31550992-1 2021 BACKGROUND: The American Diabetes Association (ADA) recommends sodium-glucose cotransporter-2 (SGLT2) inhibitors as the second medication to be started, after metformin, for patients with chronic kidney disease (CKD). Metformin 159-168 solute carrier family 5 member 2 Homo sapiens 63-93 31550992-1 2021 BACKGROUND: The American Diabetes Association (ADA) recommends sodium-glucose cotransporter-2 (SGLT2) inhibitors as the second medication to be started, after metformin, for patients with chronic kidney disease (CKD). Metformin 159-168 solute carrier family 5 member 2 Homo sapiens 95-100 33975892-3 2021 SGLT-2 inhibitors and GLP-1 receptor agonists are traditionally used in people with elevated glucose level after metformin treatment. Metformin 113-122 solute carrier family 5 member 2 Homo sapiens 0-6 33311577-3 2021 Here we found that background treatment with metformin diminished the SGLT2i-induced reductions in eGFR after 3 months of SGLT2i therapy in patients with type 2 diabetes and hypertension (-2.29 +- 0.90 vs -5.85 +- 1.27 mL/min/1.73 m2 for metformin users (n = 126) and nonusers (n = 97), respectively). Metformin 45-54 solute carrier family 5 member 2 Homo sapiens 70-75 33311577-3 2021 Here we found that background treatment with metformin diminished the SGLT2i-induced reductions in eGFR after 3 months of SGLT2i therapy in patients with type 2 diabetes and hypertension (-2.29 +- 0.90 vs -5.85 +- 1.27 mL/min/1.73 m2 for metformin users (n = 126) and nonusers (n = 97), respectively). Metformin 238-247 solute carrier family 5 member 2 Homo sapiens 70-75 33311577-6 2021 Next, we evaluated the interaction between metformin and RASis in the eGFR responses to SGLT2is. Metformin 43-52 solute carrier family 5 member 2 Homo sapiens 88-93 33856655-2 2021 Recently, clinical guidelines have focussed on patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) and recommend a sodium-glucose co-transporter 2 (SGLT2) inhibitor or a glucagon-like peptide 1 (GLP-1) receptor agonist as second-line treatment after metformin or independently of baseline glycated haemogloblin A1c (HbA1c). Metformin 279-288 solute carrier family 5 member 2 Homo sapiens 177-182 33311577-7 2021 Under no background treatment with RASis, metformin abrogated the eGFR response to SGLT2is, but this response was preserved when RASis had been given along with metformin (decreases of 0.75 +- 1.28 vs. 4.60 +- 1.15 mL/min/1.73 m2 in eGFR, p = 0.028). Metformin 42-51 solute carrier family 5 member 2 Homo sapiens 83-88 33881795-7 2021 Among treatment visits where a single drug was prescribed, use of metformin declined from 57.0% of monotherapy in 2015 to 46.0% of monotherapy in 2019, while during the same period the share of monotherapy accounted for by Glucagon-like peptide -1 (GLP-1) agonists increased from 4.3% to 8.5% and the share accounted for by sodium-glucose cotransporter-2 (SGLT-2) inhibitors increased from 7.3% to 19.5%. Metformin 66-75 solute carrier family 5 member 2 Homo sapiens 324-354 33881795-7 2021 Among treatment visits where a single drug was prescribed, use of metformin declined from 57.0% of monotherapy in 2015 to 46.0% of monotherapy in 2019, while during the same period the share of monotherapy accounted for by Glucagon-like peptide -1 (GLP-1) agonists increased from 4.3% to 8.5% and the share accounted for by sodium-glucose cotransporter-2 (SGLT-2) inhibitors increased from 7.3% to 19.5%. Metformin 66-75 solute carrier family 5 member 2 Homo sapiens 356-362 33881795-8 2021 Among treatment visits where metformin plus another drug was prescribed, the share of second line therapy accounted for by dipeptidyl peptidase-4 (DPP-4) inhibitors decreased from 21.9% of treatment visits in 2015 to 20.8% of treatment visits in 2019; sulfonylurea use declined from 45.2% to 32.7%, use of SGLT-2 inhibitors increased from 14.5% to 21.2% and use of GLP-1 agonists increased from 9.8% to 18.2%. Metformin 29-38 solute carrier family 5 member 2 Homo sapiens 306-312 33857309-8 2021 Compared to other calorie restriction mimetics such as metformin, rapamycin, resveratrol and NAD+ precursors, SGLT2 inhibitors appear to be the most promising in the treatment of ageing-related diseases, due to its regulation of multiple longevity pathways that closely resemble that achieved by calorie restriction, and their established efficacy in reduction in cardiovascular events and all-cause mortality. Metformin 55-64 solute carrier family 5 member 2 Homo sapiens 110-115 33606884-1 2021 AIMS: To evaluate the effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) on major cardiovascular events (MACE) in metformin-naive patients with type 2 diabetes (T2D). Metformin 181-190 solute carrier family 5 member 2 Homo sapiens 32-62 33606884-1 2021 AIMS: To evaluate the effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) on major cardiovascular events (MACE) in metformin-naive patients with type 2 diabetes (T2D). Metformin 181-190 solute carrier family 5 member 2 Homo sapiens 64-70 33218786-3 2021 Glucagon-like peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors when added to metformin therapy provide the most CV benefit and should be considered in most patients. Metformin 93-102 solute carrier family 5 member 2 Homo sapiens 37-67 33747548-2 2021 Sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are second-line options after metformin, while cardiovascular outcome trials have been conducted to establish the cardiovascular safety of these antidiabetic drug classes. Metformin 178-187 solute carrier family 5 member 2 Homo sapiens 0-31 33043620-0 2021 SGLT2 inhibitors with and without metformin: a meta-analysis of cardiovascular, kidney and mortality outcomes. Metformin 34-43 solute carrier family 5 member 2 Homo sapiens 0-5 33880815-4 2021 Glucagon like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitors improve glycemic control, lower body weight and blood pressure, are recommended after lifestyle and metformin as initial therapy for diabetic patients with cardiovascular or kidney comorbidities regarding their cardiorenal benefits. Metformin 206-215 solute carrier family 5 member 2 Homo sapiens 56-86 33880815-4 2021 Glucagon like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitors improve glycemic control, lower body weight and blood pressure, are recommended after lifestyle and metformin as initial therapy for diabetic patients with cardiovascular or kidney comorbidities regarding their cardiorenal benefits. Metformin 206-215 solute carrier family 5 member 2 Homo sapiens 88-93 33181201-0 2021 Does background metformin therapy influence the cardiovascular outcomes with SGLT-2 inhibitors in type 2 diabetes? Metformin 16-25 solute carrier family 5 member 2 Homo sapiens 77-83 32067559-8 2021 SGLT-2 inhibitors and GLP-1 agonists should be considered when patients" diabetes is no longer well controlled with metformin. Metformin 116-125 solute carrier family 5 member 2 Homo sapiens 0-6 32879144-7 2021 She was treated with metformin and canagliflozin (a sodium glucose co-transporter 2 (SGLT2) inhibitor), which ameliorated overt diurnal hyperglycemia and mild nocturnal hypoglycemia and reduced her blood HbA1c around 7%. Metformin 21-30 solute carrier family 5 member 2 Homo sapiens 52-83 32879144-7 2021 She was treated with metformin and canagliflozin (a sodium glucose co-transporter 2 (SGLT2) inhibitor), which ameliorated overt diurnal hyperglycemia and mild nocturnal hypoglycemia and reduced her blood HbA1c around 7%. Metformin 21-30 solute carrier family 5 member 2 Homo sapiens 85-90 33507658-4 2021 Currently, the best classes to add after metformin seem to be SGLT2 inhibitors and GLP-1 receptor agonists, as these molecules showed some cardiovascular and renal beneficial effects in dedicated studies. Metformin 41-50 solute carrier family 5 member 2 Homo sapiens 62-67 33420333-4 2021 We aimed to systematically synthesize the evidence on the comparative cardiovascular safety and efficacy of combination therapy with metformin-sodium-glucose cotransporter-2 inhibitors versus metformin-sulfonylureas in patients with type 2 diabetes. Metformin 133-142 solute carrier family 5 member 2 Homo sapiens 143-173 33420333-6 2021 We included randomized controlled trials of patients with type 2 diabetes who were on metformin-sodium-glucose cotransporter-2 inhibitors or metformin-sulphonylureas combination therapy at least for a year. Metformin 86-95 solute carrier family 5 member 2 Homo sapiens 96-126 32979231-0 2021 Efficacy and safety of a sodium-glucose co-transporter-2 inhibitor vs placebo as an add-on therapy for people with type 2 diabetes inadequately treated with metformin and a dipeptidyl peptidase-4 inhibitor: a systematic review and meta-analysis of randomized controlled trials. Metformin 157-166 solute carrier family 5 member 2 Homo sapiens 25-56 33043620-8 2021 SGLT2 inhibitors reduced the risk of MACE, with and without concomitant metformin use (HR 0.93, 95% CI 0.87-1.00 and HR 0.82, 95% CI 0.71-0.86 respectively; P-heterogeneity=0.14). Metformin 72-81 solute carrier family 5 member 2 Homo sapiens 0-5 32979231-8 2021 CONCLUSIONS: In comparison with placebo, add-on therapy with a sodium-glucose co-transporter-2 inhibitor is significantly more efficacious in lowering HbA1c , fasting plasma glucose and weight in people with type 2 diabetes following inadequate glycaemic control with metformin and a dipeptidyl peptidase-4 inhibitor. Metformin 268-277 solute carrier family 5 member 2 Homo sapiens 63-94 33189895-1 2021 AIMS: Preliminary data have suggested that metformin might potentiate cardiovascular (CV) protection by dipeptidyl peptidase-4 inhibitors (DPP-4is), but reduce CV protection by sodium-glucose cotransporter type-2 inhibitors (SGLT2is), in patients with type 2 diabetes (T2DM) at high CV-related risk. Metformin 43-52 solute carrier family 5 member 2 Homo sapiens 225-230 33120439-0 2021 Cardiovascular Safety of Sodium Glucose Cotransporter 2 Inhibitors as Add-on to Metformin Monotherapy in Patients with Type 2 Diabetes Mellitus. Metformin 80-89 solute carrier family 5 member 2 Homo sapiens 25-55 33120439-1 2021 Background: Using real-world data, cardiovascular safety was investigated in metformin users newly starting sodium glucose cotransporter 2 (SGLT2) inhibitors compared with other glucose-lowering drugs in Korea. Metformin 77-86 solute carrier family 5 member 2 Homo sapiens 108-138 33120439-9 2021 In addition, use of SGLT2 inhibitors versus sulfonylurea as add-on therapy to metformin was associated with decreased risks of HHF, all-cause mortality, HHF plus all-cause mortality, MI, stroke, and modified MACEs. Metformin 78-87 solute carrier family 5 member 2 Homo sapiens 20-25 33120439-1 2021 Background: Using real-world data, cardiovascular safety was investigated in metformin users newly starting sodium glucose cotransporter 2 (SGLT2) inhibitors compared with other glucose-lowering drugs in Korea. Metformin 77-86 solute carrier family 5 member 2 Homo sapiens 140-145 32700188-1 2020 INTRODUCTION: International guidelines recommend treatment with a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist for treatment intensification in type 2 diabetes mellitus (T2DM) patients with progression on metformin. Metformin 262-271 solute carrier family 5 member 2 Homo sapiens 66-96 32886218-5 2022 METHODS: We evaluated the hemorheological parameters of 63 patients of whom 38 received metformin with a dipeptidyl peptidase 4 (DPP-4) inhibitor, while 25 received metformin with SGLT-2 inhibitor. Metformin 165-174 solute carrier family 5 member 2 Homo sapiens 180-186 33061964-1 2020 Introduction: To conduct the first meta-analysis of randomized controlled trials (RCTs) comparing glucagon-like peptide 1 receptor agonists (GLP-1RAs) with sodium-glucose cotransporter 2 inhibitors (SGLT-2is) for obese type 2 diabetes (T2D) patients uncontrolled on metformin. Metformin 266-275 solute carrier family 5 member 2 Homo sapiens 199-205 32437914-9 2020 CONCLUSION: Our meta-analysis suggests that GLP-1RAs provide better glycaemic effects than SGLT-2is in patients with T2DM uncontrolled by metformin, albeit while increasing risk for hypoglycaemia and gastrointestinal adverse events. Metformin 138-147 solute carrier family 5 member 2 Homo sapiens 91-97 32700188-1 2020 INTRODUCTION: International guidelines recommend treatment with a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist for treatment intensification in type 2 diabetes mellitus (T2DM) patients with progression on metformin. Metformin 262-271 solute carrier family 5 member 2 Homo sapiens 98-104 32061625-0 2020 Does Metformin Interfere With the Cardiovascular Benefits of SGLT2 Inhibitors? Metformin 5-14 solute carrier family 5 member 2 Homo sapiens 61-66 32821142-0 2020 SGLT2 Inhibitors as Add-On Therapy to Metformin for People with Type 2 Diabetes: A Review of Placebo-Controlled Trials in Asian versus Non-Asian Patients. Metformin 38-47 solute carrier family 5 member 2 Homo sapiens 0-5 32274915-5 2020 Metformin seems to be safe and presents evident positive effects on insulin sensitivity, but long-term and consistent data are still missing to establish its role in the paediatric population and the possible effectiveness of other emergent treatments such as glucagon-like peptide-1 (GLP-1) analogues, dipeptidylpeptidase-4 (DPP-4) inhibitors, dual inhibitors of SGLT1 and SGLT2 and weight loss drugs. Metformin 0-9 solute carrier family 5 member 2 Homo sapiens 374-379 32598218-18 2020 In patients at increased cardiovascular risk receiving metformin-based background therapy, specific GLP-1 RAs and SGLT-2 inhibitors have a favorable effect on certain cardiovascular outcomes. Metformin 55-64 solute carrier family 5 member 2 Homo sapiens 114-120 32331584-1 2020 The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial." Metformin 159-168 solute carrier family 5 member 2 Homo sapiens 37-42 31778746-7 2020 In the future early combination therapy of metformin e.g. with SGLT-2 inhibitors should be more often used. Metformin 43-52 solute carrier family 5 member 2 Homo sapiens 63-69 31806203-3 2019 This meta-analysis was conducted to quantitatively pool the incremental net benefit of SGLT2 inhibitors in T2DM patients who failed metformin monotherapy. Metformin 132-141 solute carrier family 5 member 2 Homo sapiens 87-92 31407866-5 2020 The observed improvements in CV and renal outcomes with SGLT-2is in CVOTs suggest a class effect in this patient population and have influenced treatment guidelines for the way add-on therapy to metformin is initiated in patients with T2D and high CV risk. Metformin 195-204 solute carrier family 5 member 2 Homo sapiens 56-62 31791665-0 2020 The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial. Metformin 159-168 solute carrier family 5 member 2 Homo sapiens 37-42 31694774-10 2020 SGLT2 inhibitors induced a higher risk for diabetic ketoacidosis (DKA) than metformin/placebo. Metformin 76-85 solute carrier family 5 member 2 Homo sapiens 0-5 31359366-4 2019 Regarding overweight patients inadequately controlled with metformin, treatment with a sodium-glucose transport protein 2 inhibitor (SGLT2-I) is preferred over treatment with a dipeptidyl peptidase-4 inhibitor (DPP4-I). Metformin 59-68 solute carrier family 5 member 2 Homo sapiens 133-138 31410711-9 2019 Furthermore, there is growing evidence to illustrate the overall safety profile of this class of agents and support the benefit-risk profile of SGLT2 inhibitors as a preferred option following metformin monotherapy failure, with respect to both kidney disease progression and heart failure outcomes. Metformin 193-202 solute carrier family 5 member 2 Homo sapiens 144-149 30930073-5 2019 The overview sums up the approaches implicated by the study that can potentially counteract the detrimental impact of hyperglycemia on vascular function in people with diabetes, including the clinical use of SGLT2 inhibitors for those with type 2 diabetes already being treated, for example, with metformin, along with dietary supplementation with broccoli-derived sulforaphane and tetrahydrobiopterin. Metformin 297-306 solute carrier family 5 member 2 Homo sapiens 208-213 31440988-3 2019 Given the results from recent studies, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) recommend that patients with T2D and clinical cardiovascular disease (CVD) with inadequate glucose control despite treatment with metformin should receive an SGLT2 inhibitor or GLP-1 receptor agonist. Metformin 271-280 solute carrier family 5 member 2 Homo sapiens 299-304 30697897-6 2019 In as-treated analysis, the estimated hazard of LEA was increased among SGLT2 inhibitor initiators compared to DPP-4 inhibitor initiators (aHR 1.69, 95% CI 1.20-2.38), but not compared to SU initiators (aHR 1.02, 95% CI 0.67-1.55) or non-metformin, non-SGLT2 inhibitor initiators (aHR 1.02, 95% CI 0.54-1.93). Metformin 238-247 solute carrier family 5 member 2 Homo sapiens 72-77 31489272-4 2019 We report a novel complication of hypoglycemia that occurred during the course of treatment of SGLT2 inhibitor-induced DKA in a patient with type 2 diabetes mellitus (T2DM) on the dapagliflozin-metformin combination. Metformin 194-203 solute carrier family 5 member 2 Homo sapiens 95-100 31271575-0 2019 Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes mellitus with inadequate glycemic control on metformin: a meta-analysis. Metformin 129-138 solute carrier family 5 member 2 Homo sapiens 23-53 31120717-14 2019 CONCLUSIONS: In the United States, sequential addition of SGLT2 inhibitors to DPP-4 inhibitors may be considered cost-effective compared with traditional treatment with generic medications for patients who fail to achieve glycemic goal on metformin. Metformin 239-248 solute carrier family 5 member 2 Homo sapiens 58-63 31375850-9 2019 The use of SGLT-2 inhibitors is recommended in current guidelines and consensus statements as primary combination partners for metformin in patients with type 2 diabetes and established CV disease, high CV risk, heart failure or kidney disease. Metformin 127-136 solute carrier family 5 member 2 Homo sapiens 11-17 30767126-16 2019 There is a need to inculcate GLP-1 analogs and SGLT2 inhibitors that reduce major CV events and heart failure hospitalizations (alongside lifestyle management and metformin) in the treatment of patients with diabetes and CV disease. Metformin 163-172 solute carrier family 5 member 2 Homo sapiens 47-52 31041606-0 2019 Sodium-Glucose Co-Transporter 2 Inhibitors Compared with Sulfonylureas in Patients with Type 2 Diabetes Inadequately Controlled on Metformin: A Meta-Analysis of Randomized Controlled Trials. Metformin 131-140 solute carrier family 5 member 2 Homo sapiens 0-31 31041606-2 2019 This meta-analysis was to compare the efficacy and safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors with sulfonylureas (SUs) as second-line therapy in patients with T2DM inadequately controlled on metformin. Metformin 209-218 solute carrier family 5 member 2 Homo sapiens 94-99 31041606-11 2019 CONCLUSIONS: Despite similar glycemic efficacy in a relatively short term, SGLT2 inhibitors are more effective in the longer term than SUs as add-on to metformin. Metformin 152-161 solute carrier family 5 member 2 Homo sapiens 75-80 31148423-5 2019 These favorable effects place them, like SGLT-2 inhibitors, as a second option in the case of unsatisfactory glycemic control after metformin and dietary and lifestyle measures. Metformin 132-141 solute carrier family 5 member 2 Homo sapiens 41-47 30835599-2 2019 In patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or those at high risk for CVD, subsequently to lifestyle changes and metformin therapy, the administration of an SGLT-2 inhibitor with established benefits for cardiovascular outcome (CVOT) should be considered. Metformin 153-162 solute carrier family 5 member 2 Homo sapiens 197-203 30502742-3 2019 Metformin, in use for 60 years, is the first choice drug for type 2 diabetes and based on pre-clinical and clinical data metformin has proven cardiovascular protective actions; in contrast SGLT2 inhibitors were only introduced in 2013 but show great promise. Metformin 0-9 solute carrier family 5 member 2 Homo sapiens 189-194 30933547-1 2019 INTRODUCTION: Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) are recommended after metformin for a large spectrum of patients with type 2 diabetes, because of a favorable benefit/risk profile despite a variety of adverse events. Metformin 93-102 solute carrier family 5 member 2 Homo sapiens 62-67 30565386-0 2019 Cost-effectiveness of intensification with sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes on metformin and sitagliptin vs direct intensification with insulin in the United Kingdom. Metformin 122-131 solute carrier family 5 member 2 Homo sapiens 43-74 30565386-10 2019 CONCLUSIONS: For UK patients with T2D not at goal on metformin and sitagliptin therapy, treatment intensification with SGLT2 inhibitors prior to NPH insulin is cost-neutral or cost-effective compared with immediate NPH insulin intensification. Metformin 53-62 solute carrier family 5 member 2 Homo sapiens 119-124 30724637-3 2019 Areas covered: Ertugliflozin and metformin hydrochloride (ertugliflozin/metformin, SEGLUROMET) is a recently approved fixed-dose combination tablet containing the sodium-glucose co-transporter 2 (SGLT-2) inhibitor ertugliflozin and metformin. Metformin 33-56 solute carrier family 5 member 2 Homo sapiens 196-202 30639796-4 2019 Recent clinical guidelines have suggested the use of SGLT2 inhibitors as add-on therapy in patients for whom metformin alone does not achieve glycemic targets, or as initial dual therapy with metformin in patients who present with higher glycated hemoglobin (HbA1c) levels. Metformin 109-118 solute carrier family 5 member 2 Homo sapiens 53-58 30724637-3 2019 Areas covered: Ertugliflozin and metformin hydrochloride (ertugliflozin/metformin, SEGLUROMET) is a recently approved fixed-dose combination tablet containing the sodium-glucose co-transporter 2 (SGLT-2) inhibitor ertugliflozin and metformin. Metformin 33-42 solute carrier family 5 member 2 Homo sapiens 196-202 30724637-3 2019 Areas covered: Ertugliflozin and metformin hydrochloride (ertugliflozin/metformin, SEGLUROMET) is a recently approved fixed-dose combination tablet containing the sodium-glucose co-transporter 2 (SGLT-2) inhibitor ertugliflozin and metformin. Metformin 33-56 solute carrier family 5 member 2 Homo sapiens 163-194 29516618-6 2018 In cross-sectional analysis, greater prescribing of metformin and analogue insulin were associated with a higher proportion of patients achieving HbA1c <=58 mmol/mol; the use of SGLT2 inhibitors and metformin was associated with a reduced proportion of patients with HbA1c >86 mol/mol; otherwise associations for sulphonylureas, GLP-1 analogues, SGLT2 inhibitors and DPP-4 inhibitors were neutral or negative. Metformin 52-61 solute carrier family 5 member 2 Homo sapiens 181-186 30008267-10 2018 Weight loss from baseline was greatest in patients treated with metformin plus either an SGLT-2 inhibitor (-4.2 kg) or a DPP-4 inhibitor (-1.5 kg). Metformin 64-73 solute carrier family 5 member 2 Homo sapiens 89-95 30008267-12 2018 CONCLUSIONS: In this population-based cohort, all second-line therapies added to metformin monotherapy improved glycaemic control, but the lowest treatment change/discontinuation rate and most sustained weight loss was seen with patients receiving metformin plus an SGLT-2 inhibitor. Metformin 248-257 solute carrier family 5 member 2 Homo sapiens 266-272 30013414-2 2018 The addition of the sodium-glucose cotransporter-2 (SGLT2) inhibitor, empagliflozin, to metformin therapy has been shown to be effective and well tolerated in patients with T2DM and is 1 of the several recommended treatment options. Metformin 88-97 solute carrier family 5 member 2 Homo sapiens 20-50 30013414-2 2018 The addition of the sodium-glucose cotransporter-2 (SGLT2) inhibitor, empagliflozin, to metformin therapy has been shown to be effective and well tolerated in patients with T2DM and is 1 of the several recommended treatment options. Metformin 88-97 solute carrier family 5 member 2 Homo sapiens 52-57 30509271-2 2018 Metformin and recent antidiabetic drugs, SGLT2 inhibitors, reduce cardiovascular events. Metformin 0-9 solute carrier family 5 member 2 Homo sapiens 41-46 30219950-6 2018 Three scenarios were designed for the prescribing pattern for SGLT-2 inhibitors: (1) monotherapy, (2) metformin-based (m-based) drug prescriptions, and (3) metformin and sulfonylurea-based (m-s-based) drug prescriptions. Metformin 102-111 solute carrier family 5 member 2 Homo sapiens 62-68 30219950-6 2018 Three scenarios were designed for the prescribing pattern for SGLT-2 inhibitors: (1) monotherapy, (2) metformin-based (m-based) drug prescriptions, and (3) metformin and sulfonylurea-based (m-s-based) drug prescriptions. Metformin 156-165 solute carrier family 5 member 2 Homo sapiens 62-68 30068236-1 2018 INTRODUCTION: Metformin is the first-line glucose-lowering medication in type 2 diabetes mellitus (T2DM), but it generally requires soon or later the addition of a second-line therapy, among which a sodium-glucose cotransporter type 2 (SGLT-2) inhibitor, to reach and maintain adequate glucose control. Metformin 14-23 solute carrier family 5 member 2 Homo sapiens 199-234 30068236-1 2018 INTRODUCTION: Metformin is the first-line glucose-lowering medication in type 2 diabetes mellitus (T2DM), but it generally requires soon or later the addition of a second-line therapy, among which a sodium-glucose cotransporter type 2 (SGLT-2) inhibitor, to reach and maintain adequate glucose control. Metformin 14-23 solute carrier family 5 member 2 Homo sapiens 236-242 30068236-2 2018 Areas covered: This narrative review provides an analysis of both efficacy and safety of a dual therapy combining metformin and empagliflozin, a SGLT-2 inhibitor that has proven its" potential to reduce major cardiovascular (CV) events, mortality, and renal outcomes in patients with T2DM and established CV disease. Metformin 114-123 solute carrier family 5 member 2 Homo sapiens 145-151 29516618-6 2018 In cross-sectional analysis, greater prescribing of metformin and analogue insulin were associated with a higher proportion of patients achieving HbA1c <=58 mmol/mol; the use of SGLT2 inhibitors and metformin was associated with a reduced proportion of patients with HbA1c >86 mol/mol; otherwise associations for sulphonylureas, GLP-1 analogues, SGLT2 inhibitors and DPP-4 inhibitors were neutral or negative. Metformin 52-61 solute carrier family 5 member 2 Homo sapiens 352-357 29516618-6 2018 In cross-sectional analysis, greater prescribing of metformin and analogue insulin were associated with a higher proportion of patients achieving HbA1c <=58 mmol/mol; the use of SGLT2 inhibitors and metformin was associated with a reduced proportion of patients with HbA1c >86 mol/mol; otherwise associations for sulphonylureas, GLP-1 analogues, SGLT2 inhibitors and DPP-4 inhibitors were neutral or negative. Metformin 202-211 solute carrier family 5 member 2 Homo sapiens 352-357 29375082-6 2018 Treatment with SGLT2 inhibitors as add-on to metformin and sulfonylurea was also associated with significant reductions in blood pressure and triglycerides and increase in high-density lipoprotein-cholesterol. Metformin 45-54 solute carrier family 5 member 2 Homo sapiens 15-20 29984503-5 2018 The cardiovascular benefits of SGLT-2 inhibitors and some glucagon-like peptide-1 receptor agonists suggest that they may be the preferred choice, usually as an add-on to metformin, for patients with type 2 diabetes mellitus at high cardiovascular risk. Metformin 171-180 solute carrier family 5 member 2 Homo sapiens 31-37 29174215-11 2017 IMPLICATIONS: Although both DPP-4i and SGLT2i are effective add-on antihyperglycemic therapies to metformin monotherapy, baseline characteristics, such as HbA1C, renal function, and age, should be considered when choosing between the 2 classes to allow for optimal and timely diabetes management. Metformin 98-107 solute carrier family 5 member 2 Homo sapiens 39-44 29412124-3 2018 The newest antidiabetic drugs, possibly with the most pleiotropic actions after metformin are the sodium-glucose cotransporter 2 (SGLT-2) inhibitors (SGLT-2i). Metformin 80-89 solute carrier family 5 member 2 Homo sapiens 98-128 29412124-3 2018 The newest antidiabetic drugs, possibly with the most pleiotropic actions after metformin are the sodium-glucose cotransporter 2 (SGLT-2) inhibitors (SGLT-2i). Metformin 80-89 solute carrier family 5 member 2 Homo sapiens 130-136 28797524-0 2017 Systematic review of metformin monotherapy and dual therapy with sodium glucose co-transporter 2 inhibitor (SGLT-2) in treatment of type 2 diabetes mellitus. Metformin 21-30 solute carrier family 5 member 2 Homo sapiens 108-114 28797524-2 2017 Addition of sodium glucose cotransporter 2 inhibitor (SGLT2) will improve the glycemic control in patients on metformin alone. Metformin 110-119 solute carrier family 5 member 2 Homo sapiens 12-52 28797524-9 2017 CONCLUSION: The combined therapy of SGLT2 inhibitor along with metformin is more effective in HbA1c reduction and weight reduction as compared to monotherapy using metformin alone. Metformin 164-173 solute carrier family 5 member 2 Homo sapiens 36-41 28797524-2 2017 Addition of sodium glucose cotransporter 2 inhibitor (SGLT2) will improve the glycemic control in patients on metformin alone. Metformin 110-119 solute carrier family 5 member 2 Homo sapiens 54-59 28332871-6 2017 Recent clinical evidence shows that SGLT2 inhibitor/DPP-4 inhibitor therapy is an effective combination for T2DM treatment, providing glycated hemoglobin (HbA1c) reductions of 1.1 to 1.5%, and weight reductions of approximately 2 kg when added to metformin, which is its primary place in therapy. Metformin 247-256 solute carrier family 5 member 2 Homo sapiens 36-41 28332871-7 2017 CONCLUSION: The combination of an SGLT2 inhibitor/DPP-4 inhibitor is a safe and effective treatment choice for patients with T2DM who are unable to obtain adequate glycemic control with metformin therapy, cannot use metformin, or have a higher baseline HbA1c. Metformin 186-195 solute carrier family 5 member 2 Homo sapiens 34-39 28332871-7 2017 CONCLUSION: The combination of an SGLT2 inhibitor/DPP-4 inhibitor is a safe and effective treatment choice for patients with T2DM who are unable to obtain adequate glycemic control with metformin therapy, cannot use metformin, or have a higher baseline HbA1c. Metformin 216-225 solute carrier family 5 member 2 Homo sapiens 34-39 28276972-6 2017 Insulin basal therapy (+- metformin) may be optimized by the addition of a SGLT2 inhibitor or a glucagon-like peptide-1 (GLP-1) receptor agonist. Metformin 23-35 solute carrier family 5 member 2 Homo sapiens 75-80 28682870-8 2017 SGLT2 inhibitors as add-on to metformin treatment reduced % HbA1c significantly more than non-SGLT2 combinations after 52 weeks (P = .002) as well as after 104 weeks (P < .00001). Metformin 30-39 solute carrier family 5 member 2 Homo sapiens 0-5 28682870-11 2017 CONCLUSION: As add-on to metformin treatment, SGLT2 inhibitors are found significantly more efficacious than non-SGLT2 inhibitor combinations in the management of type 2 diabetes mellitus, although, SGLT2 inhibitor therapy is associated with significantly higher incidence of suspected or confirmed genital tract infections. Metformin 25-34 solute carrier family 5 member 2 Homo sapiens 46-51 28542373-6 2017 The relative risks of all-cause mortality with SGLT2 inhibitor use were 0.68 (95% credible interval: 0.57-0.80), 0.74 (0.49-1.10), 0.63 (0.46-0.87), 0.71 (0.55-0.90), and 0.65 (0.54-0.78), compared with placebo, metformin, sulfonylurea, TZD, and DPP4 inhibitor, respectively. Metformin 212-221 solute carrier family 5 member 2 Homo sapiens 47-52 28542373-7 2017 The relative risks of cardiovascular-related mortality with SGLT2 inhibitor use were 0.61 (0.50-0.76), 0.81(0.36-1.90), 0.52(0.31-0.88), 0.66(0.49-0.91), and 0.61(0.48-0.77), compared with placebo, metformin, sulfonylurea, TZD, and DPP4 inhibitor, respectively. Metformin 198-207 solute carrier family 5 member 2 Homo sapiens 60-65 28152176-0 2017 Metformin-SGLT2, Dehydration, and Acidosis Potential. Metformin 0-9 solute carrier family 5 member 2 Homo sapiens 10-15 28105986-5 2017 This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium-glucose co-transporter 2 (SGLT2) inhibitors. Metformin 78-87 solute carrier family 5 member 2 Homo sapiens 108-139 27995594-4 2017 METHODS: We aimed to evaluate the relative efficacy, using network meta-analysis (NMA), of treatment intensification with liraglutide and SGLT-2 inhibitors people with T2DM who have been treated with metformin (alone or in combination with SU, DPP-4, and TZD). Metformin 200-209 solute carrier family 5 member 2 Homo sapiens 138-144 28105986-5 2017 This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium-glucose co-transporter 2 (SGLT2) inhibitors. Metformin 78-87 solute carrier family 5 member 2 Homo sapiens 141-146 28760225-5 2016 Due to their insulin-independent mechanism of action, SGLT2 inhibitors can be used in monotherapy, in patients with metformin intolerance, or in combination with other glucose-lowering drugs, including insulin. Metformin 116-125 solute carrier family 5 member 2 Homo sapiens 54-59 27495291-13 2016 TRIAL REGISTRATION: Clinical trial registry name: CANagliflozin Treatment And Trial Analysis-Sulfonylurea (CANTATA-SU) SGLT2 Add-on to Metformin Versus Glimepiride. Metformin 135-144 solute carrier family 5 member 2 Homo sapiens 119-124 27268470-10 2016 The significantly decreased cardiovascular risk associated with empagliflozin SGLT-2 inhibitor therapy is impressive and may change how practitioners prescribe add-on therapy to metformin. Metformin 178-187 solute carrier family 5 member 2 Homo sapiens 78-84 25644093-8 2015 These results indicate that SGLT2 inhibitors can be successfully added to metformin plus sulfonylurea regimens. Metformin 74-83 solute carrier family 5 member 2 Homo sapiens 28-33 26854518-2 2016 SGLT-2 inhibitors may be prescribed alone or as add-on treatment in patients receiving metformin, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, and/or insulin across the natural history of the disease. Metformin 87-96 solute carrier family 5 member 2 Homo sapiens 0-6 27042132-0 2016 Sodium-glucose cotransporter-2 inhibitor combination therapy to optimize glycemic control and tolerability in patients with type 2 diabetes: focus on dapagliflozin-metformin. Metformin 164-173 solute carrier family 5 member 2 Homo sapiens 0-30 27042132-3 2016 This review focuses on the combination of metformin with dapagliflozin, a member of the SGLT-2 inhibitor class of antidiabetes agents. Metformin 42-51 solute carrier family 5 member 2 Homo sapiens 88-94 26911584-4 2016 ELIGIBILITY CRITERIA: Randomised controlled trials assessing the efficacy of SGLT-2 inhibitors in patients with type 2 diabetes inadequately controlled with diet and exercise alone or metformin monotherapy. Metformin 184-193 solute carrier family 5 member 2 Homo sapiens 77-83 25216510-11 2015 CONCLUSIONS: Dual inhibition of SGLT1/SGLT2 with LX4211 produced significant dose-ranging improvements in glucose control without dose-increasing glucosuria and was associated with reductions in weight and systolic BP in metformin-treated patients with type 2 diabetes. Metformin 221-230 solute carrier family 5 member 2 Homo sapiens 38-43 25671589-1 2015 Dapagliflozin (Farxiga), alone, or in the fixed dose combination with metformin (Xigduo), is an orally active, highly selective, reversible inhibitor of sodium-glucose cotransporter type 2 (SGLT2) that is marketed in United States, Europe, and many other countries for the treatment of type 2 diabetes mellitus. Metformin 70-79 solute carrier family 5 member 2 Homo sapiens 153-188 25671589-1 2015 Dapagliflozin (Farxiga), alone, or in the fixed dose combination with metformin (Xigduo), is an orally active, highly selective, reversible inhibitor of sodium-glucose cotransporter type 2 (SGLT2) that is marketed in United States, Europe, and many other countries for the treatment of type 2 diabetes mellitus. Metformin 70-79 solute carrier family 5 member 2 Homo sapiens 190-195 25812364-4 2015 Caution is advised to avoid use of metformin in patients at risk for lactic acidosis (e.g., in patients with advanced renal and liver insufficiency, infection, dehydration, alcoholism, or in those using diuretics or SGLT2 inhibitor). Metformin 35-44 solute carrier family 5 member 2 Homo sapiens 216-221 25554070-9 2014 Furthermore, the combination of SGLT-2 inhibitors with other drugs that either have anorectic effects (such as incretin-based therapies) or reduce hepatic glucose output (like metformin) and, thus, may dampen these two compensatory mechanisms appears appealing for the management of type 2 diabetes mellitus. Metformin 176-185 solute carrier family 5 member 2 Homo sapiens 32-38 24829965-6 2014 Moreover, the use of DPP-4 or SGLT-2 inhibitors significantly decreased risk of diarrhoea compared with placebo, when given concomitantly with metformin. Metformin 143-152 solute carrier family 5 member 2 Homo sapiens 30-36 25246775-9 2014 However, given current safety and efficacy data, SGLT2 inhibitors may present an attractive option for T2DM patients who are failing with metformin monotherapy, especially if weight is part of the underlying treatment consideration. Metformin 138-147 solute carrier family 5 member 2 Homo sapiens 49-54 25015317-1 2014 AIMS: In search of add-on treatments to metformin, sodium-glucose cotransporter-2 (SGLT-2) inhibitors are potential candidates. Metformin 40-49 solute carrier family 5 member 2 Homo sapiens 83-89 25015317-2 2014 This meta-analysis examines the potential use of SGLT-2 inhibitors in combination with metformin as a therapeutic option for type 2 diabetes management in patients with inadequate control with metformin. Metformin 193-202 solute carrier family 5 member 2 Homo sapiens 49-55 19943222-1 2009 Dapagliflozin (BMS-512148), a specific inhibitor of the sodium-glucose cotransporter SGLT2, is under development by AstraZeneca plc and Bristol-Myers Squibb Co for the potential oral treatment of type 2 diabetes mellitus (T2DM); a fixed-dose combination of dapagliflozin and metformin is also being developed by the companies for the potential treatment of diabetes mellitus. Metformin 275-284 solute carrier family 5 member 2 Homo sapiens 85-90 24007456-14 2013 DISCUSSION: This is the largest study to compare the efficacy and safety of an SGLT2 inhibitor with an SU in patients with T2DM inadequately controlled on metformin to date. Metformin 155-164 solute carrier family 5 member 2 Homo sapiens 79-84