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ABSTRACT Objectives To provide a meta-analysis of the clinical efficacy and safety of sodium glucose co-transporter 2 inhibitors (SGLT2-i), as a combination treatment with metformin in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control with metformin alone. Materials and methods We have searched randomized controlled trials (RCTs) in the database: MEDLINE, Embase and Cochrane Collaborative database. We used mean differences (MD) to assess the efficacy of glycemic and other clinical parameters, and risk ratios (RR) to evaluate the adverse events for safety endpoints. The heterogeneity was evaluated by I2. Results Finally 9 studies were included. SGLT2-i plus metformin had higher reduction level in HbA1C [MD = -0.50, 95% CI (-0.62, -0.38), p < 0.00001], FPG [MD = -1.12, 95%CI (-1.38, -0.87), p < 0.00001], body weight [MD = -1.72, 95% CI (-2.05, -1.39), p < 0.00001], SBP [MD = -4.44, 95% CI (-5.45, -3.43), p < 0.00001] and DBP [MD = -1.74, 95% CI (-2.40, -1.07), p < 0.00001] compared with metformin monotherapy. However, SGLT2-i plus metformin group had higher risk of genital infection [RR = 3.98, 95% CI (2.38, 6.67), p < 0.00001]. No significant difference was found in the risk of hypoglycemia, urinary tract infection or volume related adverse events. Conclusions Although the risk of genital infection may increase, SGLT2-i plus metformin may provide an attractive treatment option to those T2DM patients who are unable to achieve glycemic control with metformin alone, based on its effects on glycemic control, reducing body weight and lowering blood pressure.
Subject(s)
Humans , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Metformin/administration & dosage , Randomized Controlled Trials as Topic , Drug Therapy, Combination , Sodium-Glucose Transporter 2 Inhibitors/administration & dosageABSTRACT
OBJECTIVES: To provide a meta-analysis of the clinical efficacy and safety of sodium glucose co-transporter 2 inhibitors (SGLT2-i), as a combination treatment with metformin in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control with metformin alone. MATERIALS AND METHODS: We have searched randomized controlled trials (RCTs) in the database: MEDLINE, Embase and Cochrane Collaborative database. We used mean differences (MD) to assess the efficacy of glycemic and other clinical parameters, and risk ratios (RR) to evaluate the adverse events for safety endpoints. The heterogeneity was evaluated by I2. RESULTS: Finally 9 studies were included. SGLT2-i plus metformin had higher reduction level in HbA1C [MD = -0.50, 95% CI (-0.62, -0.38), p < 0.00001], FPG [MD = -1.12, 95%CI (-1.38, -0.87), p < 0.00001], body weight [MD = -1.72, 95% CI (-2.05, -1.39), p < 0.00001], SBP [MD = -4.44, 95% CI (-5.45, -3.43), p < 0.00001] and DBP [MD = -1.74, 95% CI (-2.40, -1.07), p < 0.00001] compared with metformin monotherapy. However, SGLT2-i plus metformin group had higher risk of genital infection [RR = 3.98, 95% CI (2.38, 6.67), p < 0.00001]. No significant difference was found in the risk of hypoglycemia, urinary tract infection or volume related adverse events. CONCLUSIONS: Although the risk of genital infection may increase, SGLT2-i plus metformin may provide an attractive treatment option to those T2DM patients who are unable to achieve glycemic control with metformin alone, based on its effects on glycemic control, reducing body weight and lowering blood pressure.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Metformin/administration & dosage , Sodium-Glucose Transporter 2 Inhibitors/administration & dosage , Drug Therapy, Combination , Humans , Randomized Controlled Trials as TopicABSTRACT
Relevant clinical data of 141 cases diagnosed pregestational diabetes mellitus(PGDM),diabetes mellitus in pregnancy(DIP), gestational diabetes mellitus(GDM), and type 2 diabetes mellitus(T2DM) were collected. The blood glucose control rate,insulin dose,and episode of hypoglycemia in the insulin intensive therapy were retrospectively analyzed. The results showed that there was no significant difference in the control rate among the four groups(P=0.906). The insulin dose/weight in GDM was significantly lower than those in PGDM,DIP,and T2DM groups[0.65(0.47-1.00),0.67(0.38-1.05),0.65(0.52-0.82)vs 0.45(0.29-0.61)U·kg-1·d-1,P<0.05 or P<0.01]. There was no significant difference in episode or incidence rate of hypoglycemia among the overall four groups(P=0.339). However in the patients with blood glucose reaching the control standard,the rate of hypoglycemia in T2DM was significantly higher than those in PGDM,DIP,and GDM(P<0.05 or P<0.01).
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Objective To assess the correlation between serum bilirubin levels (including direct bilirubin and indirect bilirubin) and estimated glomerular filtration rate (eGFR), urinary albumin excretion in type 2 diabetic mellitus patients. Methods A total of 2 390 patients with type 2 diabetes were included. Serum total bilirubin, direct bilirubin, indirect bilirubin, eGFR, urine albumin/uric creatinine rate (UACR) and other information were collected retrospectively. Patients were divided into 4 groups based on the total bilirubin, direct bilirubin and indirect bilirubin separately (from low to high T1 to T4 group, D1 to D4 group and I1 to I4 group). Results UACR was significantly higher in T1 group than that in T2, T3 and T4 groups: 18.79 (10.67, 53.99) mg/g vs. 15.91 (9.86, 36.12), 16.10 (9.35, 29.75) and 16.38 (9.95, 33.44) mg/g (P＜0.01); and eGFR was significantly lower. In D1 to D4 group and I1 to I4 groups, there were statistical differences in UACR and eGFR (P＜0.01). Pearson correlation analyses showed that serum total bilirubin, direct bilirubin and indirect bilirubin were positively correlated with eGFR (r＝0.107, 0.076 and 0.110; P＜0.01), and inversely correlated with UACR (r＝-0.093,-0.078 and-0.090; P ＜ 0.01). Multiple linear regression analysis showed linear relationships between serum total bilirubin, direct bilirubin, indirect bilirubin and eGFR, UACR still existed after adjustment of age, gender, duration of diabetes, BMI, glycosylated hemoglobin A1c and diastolic blood pressure (P＜0.05). Conclusions Serum total bilirubin, direct bilirubin and indirect bilirubin are all positively correlated with eGFR, and inversely correlated with UACR.
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Objective To evaluate the efficacies of different ventilatory pattern during one lung ventilation (OLV). Methods During OLV, all patients underwent two different ventilatory pattern, total volume (10ml/kg) without PEEP and half tidal volume (5ml/kg) with PEEP of 7cmH 2O. The arterial blood samples were collected for blood gases analysis immediately before one lung ventilation, 30min following two different OLV pattern and 30 min after resuming two lung ventilation. The airway pressure and hemodynamic parameters were monitored simutaneously. Results PaO 2 and PaCO 2 were higher during half tidal volume than during total tidal volume(P
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Objective: To investigate the role of endogenous nitric oxide (NO) in the pulmonary edema caused by overinfusion of colloid. Method: Forty healthy rabbits were randomly allocated into (Ⅰ) control group, (Ⅱ) infusion control group: one fold total blood volume of Gelofusine was infused at 2ml?kg~(-1)?min~(-1)(Ⅲ)L-NNA group:LNNA 20 mg/kg was intravenously injected before infusion, (Ⅳ)L-Arg+L-NNA group:L-arginine 300mg/kg and LNNA 20 mg/kg was intravenously injected before infusion. MAP,HR and CVP were recorded during the experiment, arterial blood gas analysis was examined before and after infusion,serumal NO value and lung water content were measured at the end of the experiment. Result: Overinfusion of colloid,L-NNA,an inhibitor of NO synthesis increased the extravascular lung water (EVLW) content and decreased NO value,meanwhile CVP increased,HR,PaO_2 and SaO_2 decreased,excess dose of L-arginine completely reversed the effect of L-NNA. Serumal NO value was negatively correlated with EVLW content (r=-0.94). EVLW content was significantly correlated with total lung water (r=0.41). Conclusion:Endogenous NO can reduce the pulmonary edema caused by overinfusion of colloid.
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Objective To assess the influences of cardiopulmonary bypass (CPB) on energy matabolism and the effect of nicardipine pretreatment. Methods Sixteen patients with valvlar heart disease undergoing valve replacement were chosen and randomly allocated into control group (group C, n=8) and nicardipine pretreatment group (group N,n=8). In group N, nicardipine 0.5?g?kg -1?min -1 was continuously infused after induction of anesthesia and terminated before CPB. The total dose given was 0.5mg?kg -1. If the total dose was not reached before CPB, the rest dose was given immediately after the beginning of CPB. Arterial and coronary sinus blood samples were taken immediately before CPB,at 5,30min after the aortic declamping , the end of operation, 6 and 18h after operation.Blood lactate and glucose concentrations were measured. Blood gas was checked simultaneously. Then myocardial lactate extraction rate (LER) and myocardial glucose extraction rate(GER) and myocardial oxygen extraction index(MOEI) were calculated. Results In group C GER and LER decreased signficantly after aortic declamping as compared with those before CPB (P
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Objective To determine perioperative changes of tumor necrosis factor alpha (TNF ?),superoxide dismutase(SOD),lipid peroxides(LPO) and creatine kinase MB (CK MB) in patients undergoing cardiopulmonary bypass (CPB) Methods Thirteen patients undergoing heart valves surgery were studied Blood samples were taken from artery and coronary sinus for measurement of plasma TNF ? and LPO concentrations, and plasma SOD and CK MB activities prior to CPB, 5min,30min after aorta declamping, at the end of operation, 6h and 18h after surgery respectively Blood gas analysis was done at various intervals and alveolar arterial oxygen gradient (P A a DO 2) was calculated The net myocardial release of TNF ? (coronary sinus plasma level minus arterial level) was recorded Results Arterial and coronary sinus TNF? levels increased significantly following aortic declamping as compared with those before CPB and were kept at the higher level till the end of operation (P
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ve To investigate the mechanism of myocardial ischemia-reperfusion injury during cardiac surgery and the protective effect of low dose nicardipine. Methods Sixteen patients undergoing valve replacement under cardiopulmonary bypass (CPB) were randomized to one of the two groups: control group (group C, n = 8) and nicardipine group (group N, n = 8) . In group N low dose nicardipine (O.5?g?kg-1 ?min-1) was infused after induction of anesthesia until beginning of CPB, a total dose of 0.05 mg?kg-1 was given. All patients were premedicated with intramuscular morphine 0.1-0.2 mg?kg-1 and scopolamine 0.3 mg 30 min before surgery. Anesthesia was induced with midazolam 0.05-0.1 mg?kg-1, fentanyl 15-20 ?g?kg-1 and pipecuronium 0.1 mg?kg-1 and maintained with intermittent boluses of midazolam 0.05 mg? kg-1, fentanyl 10-30?g?kg-1 and pipecuronium 2 mg. After induction of anesthesia Swan-Ganz catheter was placed for hemodynamic monitoring. Moderate hypothermia (26℃-28℃) was maintained and Hct was diluted to 20%-24% during CPB. Hyperkalemic cardioplegia was used for myocardial protection. Arterial blood (a) and coronary sinus (cs) blood were taken simultaneously for determination of tumor necrosis factor a (TNF-a), superoxide dismutase (SOD), lipid peroxide (LPO), creative kinase(CK-MB) before CPB and at 5 and 30 min after release of aortic cross-clamp (RACC), at the end of operation (EO) and at 6h and 18h after operation. Myocardial net release of TNF-a (TNF-anr) and LPO (LPOnr) and net consumption of SOD (SODnc) were calculated. The number of defibrillation after RACC, weaning index from CPB and dopamine requirement after CPB were recorded simultaneously. Results In group C LPOa and LPOcs increased significantly after RACC until the end of operation as compared with the baseline (P
