Network meta-analysis of SGLT-2 inhibitor-induced hypoglycemia risk in type 2 diabetes patients / 中国药房

OBJECTIVE To evaluate the risk of hypoglycemia caused by sodium-glucose co-transporter protein 2 （SGLT-2） inhibitors in type 2 diabetes （T2DM） patients. METHODS Retrieved from PubMed， Web of Science， Cochrane Library， CNKI， VIP， Wanfang Data and CBM， randomized controlled trials （RCTs） about SGLT-2 inhibitors in the treatment of T2DM were collected from the inception to Oct. 15th， 2022. After literature screening， data extraction and quality evaluation of included literature with bias risk assessment tool recommended by the Cochrane system evaluator handbook 5.1.0， Stata 15.1 software was used for network meta-analysis and publication bias analysis. RESULTS A total of 22 RCTs were included， with a total of 18 734 patients. The results of meta-analysis showed that compared with ertugliflozin 15 mg [RR＝3.26， 95%CI （1.13， 8.11）， P＜0.05] and ertugliflozin 25 mg [RR＝3.08， 95%CI （1.12， 6.34）， P＜0.05]， the incidence of hypoglycemia was significantly increased in patients using canagliflozin 300 mg. Compared with ertugliflozin 15 mg [RR＝1.48， 95%CI （1.24， 6.93）， P＜0.05] and ertugliflozin 25 mg [RR＝6.74， 95%CI （1.33， 9.34）， P＜0.05]， the incidence of hypoglycemia in patients treated with canagliflozin 100 mg was significantly increased. There was no statistically significant difference between other groups （P＞0.05）. The ranking results of the network meta-analysis showed that the incidence of hypoglycemia was from low to high， ie. ertugliflozin 15 mg＞placebo＞ertugliflozin 25 mg＞empgaliflozin 25 mg＞empgaliflozin 10 mg＞empgaliflozin 1 mg＞dapagliflozin 5 mg＞ dapagliflozin 10 mg＞dapagliflozin 2.5 mg＞canagliflozin 300 mg＞ertugliflozin 10 mg＞ertugliflozin 5 mg＞empgaliflozin 50 mg＞canagliflozin 200 mg＞canagliflozin 100 mg＞canag-liflozin 50 mg＞ertugliflozin 1 mg＞empgaliflozin 5 mg. Results of publication bias analysis showed that there was little possibility of publication bias in this study. CONCLUSIONS When SGLT-2 inhibitors are used in patients with T2DM， the incidence of hypoglycemia is the lowest when using ertugliflozin 15 mg， and the incidence of hypoglycemia is the highest when using empagliflozin 5 mg.

Sodium-glucose co-transporter 2 inhibitor: Cardiorenal benefit, bone metabolism, and fracture risk in type 2 diabetes mellitus / 中华内分泌代谢杂志

Type 2 diabetes mellitus is commonly associated with cardiovascular, renal complications, osteoporosis and other comorbidities. Sodium-glucose co-transporter 2 inhibitor (SGLT-2i) can reduce blood glucose level in patients with type 2 diabetes mellitus by promoting urine glucose excretion, and has the effect of weight loss and blood pressure reduction. Large randomized controlled clinical trials have shown that SGLT-2i can improve the prognosis of cardiovascular disease and diabetic nephropathy. This article focuses on the effects of SGLT-2i on cardiorenal outcomes and bone metabolism in addition to the glucose-lowering effect. SGLT-2i can improve the prognosis of patients with coronary atherosclerotic cardiovascular disease, reduce the risk of hospitalization for heart failure, reduce cardiovascular diseases and all-cause mortality, and has renal protective effect. Moreover, the cardiorenal protective effect is proved to be consistent in people without type 2 diabetes. SGLT-2i has a regulatory effect on bone mineral ions and bone metabolism related hormones, and its risk of osteoporosis and fracture deserves attention. Although data suggest that canagliflozin may increase fracture risk, meta-analyses of multiple clinical trials have concluded that SGLT-2i does not significantly increase fracture risk. However, for patients with high risk of fracture, bone mineral density and bone turnover biomarkers should be considered to assess the risk of fracture before prescription.

A 12 week prospective clinical evidence of empagliflozin efficacy in uncontrolled type 2 diabetes mellitus treated with metformin and a sulfonylurea

Background: The main aim of the study is to evaluate the efficacy of empagliflozin 10 mg once daily over 12 weeks as add-on therapy to metformin plus sulfonylurea in patients with type 2 diabetes mellitus with inadequate glycemic control.Methods: It is a prospective, observational, study conducted in patients of Sri Badhrakali Diabetic Center located in Warangal, Telangana, India. The efficacy of empagliflozin 10 mg was assessed by measuring the change in the glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), body mass index (BMI) at the baseline and 12 weeks, systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the baseline and after 24 hours of treatment.Results: In the present study, the addition of empagliflozin to metformin and Sulfonylurea therapy for 12 weeks provided 0.87 % reduction in HbA1c. The mean changes of FPG from baseline to 12-week is -26 mg/dl. At 24 hours empagliflozin significantly reduced blood pressure with mean changes of SBP and DBP -4.147 and -1.526 mmHg respectively. The mean changes in BMI from baseline to week 12 is -0.638 kg/m2.Conclusions: Empagliflozin 10 mg provided ancillary reduction in HbA1c outside of metformin and sulfonylurea. Controlled body weight, HbA1c, blood pressure decreases diabetes progression, decreased risk of diabetic complications and reduced risk for cardiovascular disorders.

Research advances in sodium-glucose co-transporter 2 inhibitor in treatment of type 2 diabetes mellitus with nonalcoholic fatty liver disease / 临床肝胆病杂志

Nonalcoholic fatty liver disease (NAFLD) is a common complication of type 2 diabetes mellitus (T2DM) and can progress to liver cirrhosis and even hepatocellular carcinoma, but there are still no effective pharmacotherapies for NAFLD at present. Sodium-glucose co-transporter 2 inhibitor (SGLT-2i) is a newly approved oral hypoglycemic agent and can effectively reduce blood glucose. Meanwhile, SGLT-2i can improve NAFLD by improving lipid accumulation and insulin resistance, exerting anti-inflammatory and anti-oxidative stress effects, reducing liver fibrosis degree, and delaying the progression to hepatocellular carcinoma. SGLT-2i also helps with the prevention of NAFLD by reducing the toxicity of high glucose, body weight, and blood uric acid and improving liver dysfunction. This article reviews the current status of T2DM with NAFLD, the mechanism of action of SGLT-2i, the effect of SGLT-2i in preventing T2DM with NAFLD, and the safety of SGLT-2i.

Short-term outcomes of patients with Type 2 diabetes mellitus treated with canagliflozin compared with sitagliptin in a real-world setting

<p><b>INTRODUCTION</b>We aimed to evaluate the effectiveness and safety of canagliflozin as compared to sitagliptin in a real-world setting among multiethnic patients with Type 2 diabetes mellitus (T2DM) in Singapore.</p><p><b>METHODS</b>This was a new-user, active-comparator, single-centre retrospective cohort study. Patients aged 18-69 years with T2DM and estimated glomerular filtration rate ≥ 60 mL/min/1.73 m were eligible for inclusion if they were initiated and maintained on a steady daily dose of canagliflozin 300 mg or sitagliptin 100 mg between 1 May and 31 December 2014, and followed up for 24 weeks.</p><p><b>RESULTS</b>In total, 57 patients (canagliflozin 300 mg, n = 22; sitagliptin 100 mg, n = 35) were included. The baseline patient characteristics in the two groups were similar, with overall mean glycated haemoglobin (HbA1c) of 9.4% ± 1.4%. The use of canagliflozin 300 mg was associated with greater reductions in HbA1c (least squares [LS] mean change -1.6% vs. -0.4%; p < 0.001), body weight (LS mean change -3.0 kg vs. 0.2 kg; p < 0.001) and systolic blood pressure (LS mean change: -9.7 mmHg vs. 0.4 mmHg; p < 0.001), as compared with sitagliptin 100 mg. About half of the patients on canagliflozin 300 mg reported mild osmotic diuresis-related side effects that did not lead to drug discontinuation.</p><p><b>CONCLUSION</b>Our findings suggest that canagliflozin was more effective than sitagliptin in reducing HbA1c, body weight and systolic blood pressure in patients with T2DM, although its use was associated with an increased incidence of mild osmotic diuresis-related side effects.</p>

The Effect and Safety of Dapagliflozin in Patients with Type 2 Diabetes: A Single-Institution Pharmacovigilance Review / 임상당뇨병

BACKGROUND: Dapagliflozin, a selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, lowers blood glucose by reducing glucose reabsorption at the proximal renal tubule in an insulin-independent manner. We aimed to evaluate the efficacy and safety of dapagliflozin and to identify the risk factors of adverse drug events in patients with type 2 diabetes. METHODS: As an institutional pharmacovigilance review activity, we reviewed data from medical records of 455 patients with type 2 diabetes who received dapagliflozin therapy from July 2014 to August 2015 in Seoul National University Hospital. We analyzed the changes in laboratory data and examined the characteristics of dapagliflozin users who showed adverse effects. RESULTS: Mean changes in HbA1c and fasting serum glucose level from baseline to second visit were −0.42% (8.07 ± 1.51% to 7.65 ± 1.31%, P < 0.001) and −22.9 mg/dL (167.8 ± 48.5 mg/dL to 144.9 ± 37.6 mg/dL, P < 0.001), respectively. Adverse drug events observed during this study were lower urinary tract symptoms (7.7%), dehydration-related symptoms (6.1%), ketonuria (3.4%), hypoglycemia (3.4%), and urogenital infection (4.2%). Thiazide use, age, insulin use, number of anti-diabetic drugs, gender and history of urogenital infection were the risk factors for adverse drug events (P < 0.05). CONCLUSION: Dapagliflozin significantly improved hyperglycemia in patients with type 2 diabetes without serious adverse drug events. The incidences of adverse drug events were was similar to those ofthat in the previous studies.

Na+-glucose cotransporter inhibitor for treatment of diabetes / 第二军医大学学报

Sodium glucose co-transporter (SGLT) is one of the transporters responsible for the resorpcion of glucose, and inhibition of its activity can decrease the resorption of glucose. Human SGLT is mainly composed of SGLT1 and SGLT2. Due to the specific distribution and the high efficiency of SGLT2, SGLT2 inhibitor is a potential new strategy for treatment diabetes. Abundant animal experiments and clinical trails have found that SGLT2 inhibitor can greatly lower the blood glucose and help to lose weights. However, the current researches about SGLT2 inhibitor are still very limited both in depth and in broadness; problems concerning the safety, efficacy and indication of SGLT2 inhibitor still need to be further studied.