Meta-analysis of Efficacy and Safety of SGLT- 2 Inhibitors Combined with Insulin for Type 1 Diabetes Mellitus / 中国药房

OBJECTIVE：To systematically evaluate the efficacy and safety of sodium-glucose co-transporter 2 （SGLT-2）inhibitors combined with insulin in the treatment of type 1 diabetes mellitus（T1DM），and to provide evidence-based reference for clinical treatment of T1DM. METHODS：Retrieved from PubMed，Cochrane library，Embase，Clinical Trials，CNKI，CBM and Wanfang database，randomized controlled trials（RCT）about SGLT-2 inhibitor（trial group）versus placebo（control group）in the treatment of T1DM based on insulin treatment were collected during the inception to Feb. 2020. After data extraction of literatures met inclusion criteria，Cochrane risk bias evaluation tool 5.1.0 was used to evaluate its quality，and Meta-analysis was perfomed by using Stata 12.0 software. RESULTS：A total of 11 RCTs were included，involving 7 003 patients. The results of Meta-analysis showed that the decrease of HbA1c [SMD＝－0.49，95％CI（－0.53，－0.44），P＜0.001]，the proportion of patients with HbA1c≥ 0.5％ and without severe hypoglycemia [OR＝3.93，95％ CI（3.49，6.21），P＜0.001]，the proportion of patients with HbA1c≥ 0.5％ [OR＝2.65，95％CI（2.25，3.12），P＜0.001]，the target rate of HbA1c level＜7.0％ [OR＝2.85，95％CI（2.44，3.33），P＜0.001] and the decrease of body weight [SMD＝－0.83，95％CI（－0.96，－0.70），P＜0.001] in trial group were significantly larger or higher than control group；the decrease values of daily insulin dosage，fasting blood glucose，postprandial blood glucose，systolic blood pressure and diastolic blood pressure in trial group were significantly higher than those in the control group，with statistical significance（P≤0.011）. The total incidence of ADR [OR＝1.14，95％CI（1.04，1.26），P＝0.007]，the incidence of SGLT-2 inhibitor related ADR [OR＝2.17，95％CI（1.75，2.99），P＜0.001]，the incidence of severe ADR [OR＝1.48，95％CI（1.24，1.77），P＜0.001]， the incidence of genital infection [OR＝3.84，95％CI（3.14，4.69），P＜0.001]，the incidence of diarrhea [OR＝1.47，95％CI（1.09，1.97），P＝0.011]，the incidence of fluid reduction related ADR [OR＝2.05，95％CI（1.37，3.08），P＝0.001]，the incidence of ketosis related ADR [OR＝4.18，95％CI（3.15，5.55），P＜0.001]，the incidence of ketoacidosis [OR＝4.33，95％CI（3.01，6.23），P＜0.001] and the incidence of severe ketoacidosis [OR＝5.06，95％CI（2.61，9.81），P＜0.001] were significantly higher than control group， with statistical significance. There was no statistical significance in the incidence of hypoglycemia，severe hypoglycemia，urinary tract infection or kidney injury between 2 groups. CONCLUSIONS：SGLT-2 inhibitors for the treatment of T1DM can significantly improve the blood glucose，reduce body weight and daily insulin dose，lower systolic blood pressure and diastolic blood pressure，while dose not increase the risk of hypoglycemia，urinary tract infections and renal impairment but increase the risk of total ADR as well as the risk of ADR such as genital infection，diarrhea，ketoacidosis，to which should be paid attention.

Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes mellitus with inadequate glycemic control on metformin: a meta-analysis

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.

Cardiovascular Outcome Trials of Sodium Glucose Cotransporter 2 Inhibitor and Its Possible Cardioprotective Mechanism

Patients with type 2 diabetes (T2D) have a significantly higher risk of developing cardiovascular diseases such as myocardial infarction, heart failure, and stroke. Current anti-diabetic drugs are highly effective for managing hyperglycemia. However, most T2D patients are still at high risk for cardiovascular disease. Over the past decade, many studies have assessed the efficacy of anti-diabetic drugs in regards to cardiovascular disease outcomes in T2D patients. However, despite the effective glycemic control of these drugs, they failed to show significant benefits that impact the morbidity and mortality of cardiovascular disease (CVD). In recent years, anti-diabetic drugs, developed with other mechanisms, have shown significant results for improving the risk of CVD. In addition, sodium glucose cotransporter 2 inhibitors have shown promising results that impact CVD outcomes in several trials. This article will review the cardiovascular outcomes and possible cardioprotective mechanisms of sodium glucose cotransporter 2 inhibitors.

Efficacy and safety of sodium glucose co-transporter 2 inhibitors(SGLT2i) in the treatment of type 2 diabetes / 中华内分泌代谢杂志

[Summary] As of 2014, an estimated 387 million people have diabetes mellitus ( DM) worldwide, which represents 8.3%of the adult population.China Noncommunicable Disease Surveillance in 2010 shows that the overall prevalence of DM is estimated to be 11.6%(approximately 113.9 million) in the Chinese adult population, with the prevalence among men of 12.1%and women of 11.0%, respectively.Control of blood glucose is fundamental to DM management.Despite the availability of several antihyperglycemic agents, only 53%of patients with DM achieve the recommended goals for DM care of HbA1C<7.0%.According to the National Health and Nutrition Examination Survey and the Behavioral Risk Factor Surveillance System Survey during the period of 10 years in the United States, 33.4%to 48.7%of persons with DM still have not met the targets for glycemic control, blood pressure or lipid level.In order to improve glycemic control, there is a need for new therapeutic options with innovative mechanisms of action and acceptable safety profiles.As a newly developed class of oral antidiabetic drugs, sodium-glucose co-transporter 2 inhibitors(SGLT2i) have recently been approved for the treatment of patients with type 2 diabetes mellitus, including canagliflozin, dapagliflozin, and empagliflozin.Evidence from clinical trials has suggested promising efficacy and safety of SGLT2i when used as monotherapy or in combination with other antihyperglycemic medications.SGLT2i significantly reduce HbA1C and fasting plasma glucose, and are well tolerated in general with a low intrinsic propensity to cause hypoglycemia, as well as rare severe renal or cardiovascular adverse events reported.

Sodium-glucose co-transporter-2 inhibitors as anti-diabetic agents: a review.

The incidence and prevalence of Type 2 diabetes mellitus (T2DM) have been increasing worldwide. However, existing therapeutic classes of anti-diabetic drugs are not adequately effective in achieving and maintaining long-term glycemic control in the most patients. The majority of the drugs control blood sugar without addressing the basic pathology of insulin resistance and relative defi ciency. Moreover, side effects such as hypoglycemia and weight gain, of both new and established drugs need to be considered prior to treating a patient. An emerging anti-hyperglycemic intervention, the sodium glucose co-transporter 2 (SGLT2) inhibitor acts by a novel mechanism. Under physiological conditions, SGLT2 accounts for 90% of the glucose re-absorption in the kidney, while the SGLT2 inhibitors result in an increase in urinary excretion of glucose and lower plasma glucose levels. Here, the pros and cons of SGLT2 inhibitors are considered, while approaching a patient with T2DM. The basic biochemistry and physiology underlying the mechanisms of SGLT2 inhibitors are discussed alongside its clinical pharmacology, with a focus on metabolic changes associated with urinary glucose loss. Finally, a consideration of Food and Drug Administration safety concerns associated with acidosis due to SGLT2 inhibitor usage is presented, to allow a complete understanding of the utility of these molecules in the light of existing T2DM therapies.