Safety Of Sodium-glucose Co-transporter 2 Inhibitors Research Articles

Combination Therapy With Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Older Patients With Type 2 Diabetes: A Real-World Evidence Study.

Scientific literature about the combination of glucagon-like peptide-1 receptor agonists (GLP-1ra) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in older patients is scarce. We sought to assess the real-world efficacy and safety of SGLT2 inhibitors and GLP-1ra combination therapy in older patients (>65 years of age). This was an observational, prospective, multicenter study based on clinical practice. Patients were stratified according to tertiles of baseline glycated hemoglobin (A1C) levels and to treatment schedule. We included 113 patients (65.5% men, mean age 70.4±8.8 years). The body mass index was 36.5 (±6.6) kg/m2. The baseline A1C level was 8.0% (±1.2%). At the 6-month follow up, we found a significant reduction in A1C levels (-1.1%; p<0.0001), body mass index (-2.1 kg/m2; p<0.00003) and systolic blood pressure (-13 mmHg; p<0.000005). Patients who had the highest baseline A1C levels (≥8.4%) showed greater improvement in A1C levels (p<0.0001), weight (p<0.0001) and quality-of-life scores (p<0.0001). The greatest reduction in A1C levels and weight was seen in patients who started both drugs simultaneously (p<0.0001). The second greatest reduction was seen when GLP-1ra was added to previous treatment with an SGLT2i (p<0.0001). Also of note was a decrease in systolic blood pressure in patients for whom an SGLT2i was added to previous GLP-1ra treatment (p<0.0001). Of the patients, 34.3% achieved the combined endpoint of A1C levels <7% and weight loss ≥5% without hypoglycemia. This study's findings provide evidence of clinically meaningful reductions in A1C level, body weight and systolic blood pressure in older patients with type 2 diabetes who are taking combined regimens. The dropout and hypoglycemia rates were minimal, and treatment was tolerated well.

Safety of Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2-I) During the Month of Ramadan in Muslim Patients with Type 2 Diabetes.

Sodium-glucose cotransporter 2 inhibitors (SGLT2-I) are a new class of antidiabetic drugs that might increase the risk of dehydration and hypoglycemia, particularly during the month of Ramadan in which Muslims abstain from eating and drinking for 14-16 hours daily. We aimed to provide real-life evidence about the safety of SGLT2-I during Ramadan. All patients over the age of 18 years on SGLT2-I before Ramadan 2016 who would be fasting during Ramadan were included. Demographic data, detailed medical history including comorbidities and medication profile, and laboratory results were collected before and after Ramadan. We also conducted a phone interview to evaluate the frequency and severity of hypoglycemia and dehydration. Of the total of 417 patients, 113 (27.0%) experienced hypoglycemic events, and 93 of these (82.3%) checked their blood glucose using a glucometer. Confirmed hypoglycemia (< 70 mg/dL) was observed in 78 (83.8%). The hypoglycemic events were significantly more frequent in the SGLT2-I plus insulin-treated group than in those treated with SGLT2-I plus oral hypoglycemic agents group (p < 0.001). Confirmed hypoglycemic events were more frequent in those using SGLT2-I plus intensive insulin compared to those using SGLT2-I plus basal insulin (p = 0.020). Symptoms of dehydration were seen in 9.3% (n = 39) of the total population. We observed statistically significant reductions in glycated hemoglobin and weight by the end of Ramadan (p < 0.001). There were no significant changes in lipid profile and creatinine levels by the end of the study. The use of insulin in combination with SGLT2-I increases the risk of hypoglycemia during Ramadan. Hypoglycemic events were mild and did not require hospital admission. However, careful monitoring during prolonged fasting is warranted. No significant harmful effects on renal function result from treatment with SGLT2-I during Ramadan.

Long-term efficacy and safety of sodium-glucose cotransporter-2 inhibitors as add-on to metformin treatment in the management of type 2 diabetes mellitus: A meta-analysis.

Background:Drug intensification is often required for patients with type 2 diabetes mellitus on stable metformin therapy. Among the potential candidates for a combination therapy, sodium-glucose transporter-2 (SGLT2) inhibitors have shown promising outcomes. This meta-analysis was performed to compare the efficacy and safety of SGLT2 inhibitors with non-SGLT2 combinations as add-on treatment to metformin.Methods:Literature search was carried out in multiple electronic databases for the acquisition of relevant randomized controlled trials (RCTs) by following a priori eligibility criteria. After the assessment of quality of the included RCTs, meta-analyses of mean differences or odds ratios (OR) were performed to achieve overall effect sizes of the changes from baseline in selected efficacy and safety endpoints reported in the individual studies. Between-studies heterogeneity was estimated with between-studies statistical heterogeneity (I2) index.Results:Six RCTs fulfilled the eligibility criteria. 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). Among other endpoints, SGLT2 inhibitors also reduced fasting plasma glucose levels, body weight, systolic, and diastolic blood pressures after 52 weeks and 104 weeks significantly (P < .00001) more than non-SGLT2 combinations. Incidence of hypoglycemia was significantly lower (P = .02) but incidence of suspected or confirmed genital tract infections was significantly higher (P < .00001) in SGLT2 inhibitors treated in comparison with non-SGLT2 combinations.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.

Sodium-glucose cotransporter-2 inhibitors and cardiovascular outcomes in type 2 diabetes mellitus: A systematic review

Sodium-glucose cotransporter - 2 (SGLT2) inhibitors are a novel class of anti-diabetics proven to reduce blood pressure, blood glucose and body weight. However, the long-term cardiovascular (CV) safety implications of these agents remain unclear. This systematic review aimed to evaluate the available clinical trial evidence pertaining to long-term cardiovascular safety of SGLT2 inhibitors. The databases EMBASE and MEDLINE were searched. Randomized controlled trials assessing CV safety of SGLT2 inhibitors compared with placebo or anti-diabetic medications were included. Two investigators independently extracted study data and completed risk of bias assessments (sequence generation, allocation concealment, blinding, incomplete outcome data, or selective outcome reporting and other biases). Outcomes included CV death, myocardial infarction, and stroke. A total of 464 studies were identified in the electronic search and 14 from other sources. Sixteen randomized clinical trials were included after full-text review. All studies reported at least one of the pre-defined outcomes (CV death, myocardial infarction, and stroke). Nineteen CV deaths were reported in SGLT2 inhibitors groups versus 10 CV deaths in placebo or other comparator arms; numerically higher in the dapagliflozin arms. The number of CV events was numerically higher in SGLT2 inhibitor groups than in other arms. Risk of bias assessment showed mixed results, with overall quality assessments deemed unclear for 6 of 16 studies (37.5%). Findings showed CV outcomes do occur in patients taking SGLT2 inhibitors yet the clinical significance remains unclear. These results can be considered hypothesis generating, as studies were limited by inadequate power and/or follow-up time. Future longitudinal studies are needed to further assess the efficacy and safety profiles of these new agents before they become widely adopted in clinical practice.

Efficacy and Safety of SGLT2 Inhibitors in Patients with Type 1 Diabetes: A Meta-analysis of Randomized Controlled Trials.

Objective To assess the efficiency and safety of a novel sodium-glucose co-transporter 2 (SGLT2) inhibitor-SGLT2 inhibitors, in combination with insulin for type 1 diabetes mellitus (T1DM). Methods We searched Medline, Embase, and the Cochrane Collaboration Library to identify the eligible studies published between January 2010 and July 2016 without restriction of language. The Food and Drug Administration (FDA) data and ClinicalTrials (http://www.clinicaltrials.gov) were also searched. The included studies met the following criteria: randomized controlled trials; T1DM patients aged between 18 and 65 years old; patients were treated with insulin plus SGLT2 inhibitors for more than 2 weeks; patients' glycosylated hemoglobin (HbA1c) levels were between 7% and 12%. The SGLT2 inhibitors group was treated with SGLT2 inhibitors plus insulin, and the placebo group received placebo plus insulin treatment. The outcomes should include one of the following items: fasting blood glucose, HbA1c, glycosuria, or adverse effects. Data were analyzed by two physicians independently. The risk of bias was evaluated by using the Cochrane Collaboration's Risk of Bias tool and heterogeneity among studies was assessed using Chi-square test. Random effect model was used to analyze the treatment effects with Revman 5.3.Results Three trials including 178 patients were enrolled. As compared to the placebo group, SGLT2 inhibitor absolutely decreased fasting blood glucose [mean differences (MD) -2.47 mmol/L, 95% confidence interval (CI) -3.65 to -1.28, P<0.001] and insulin dosage (standardized MD -0.75 U, 95%CI -1.17 to -0.33, P<0.001). SGLT2 inhibitors could also increase the excretion of urine glucose (MD 131.09 g/24 h, 95%CI 91.79 to 170.39, P<0.001). There were no significant differences in the incidences of hyperglycemia [odds ratio (OR) 1.82, 95%CI 0.63 to 5.29, P=0.27], urinary tract infection (OR 0.95, 95%CI 0.19 to 4.85, P=0.95), genital tract infection (OR 0.27, 95%CI 0.01 to 7.19, P=0.43), and diabetic ketoacidosis (OR 6.03, 95%CI 0.27 to 135.99, P=0.26) between the two groups.Conclusion SGLT2 inhibitors combined with insulin might be an efficient and safe treatment modality for T1DM patients.

Efficacy and safety of sodium glucose co-transporter 2 inhibitors(SGLT2i) in the treatment of type 2 diabetes

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. (Chin J Endocrinol Metab, 2016, 32: 171-176) Key words: Diabetes mellitus, type 2; Sodium-glucose co-transporter 2 inhibitors; Dapagliflozin; Efficacy; Safety

Sodium–Glucose Cotransporter 2 Inhibitors for Type 2 Diabetes

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs. To assess the efficacy and safety of SGLT2 inhibitors in adults with type 2 diabetes. MEDLINE, EMBASE, and the Cochrane Library from inception through April 2013 without language restrictions; regulatory authorities' reports; and gray literature. Randomized trials comparing SGLT2 inhibitors with placebo or other medication for type 2 diabetes. Three reviewers extracted or checked data for study characteristics, outcomes of interest, and risk of bias, and 3 reviewers summarized strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Sodium-glucose cotransporter 2 inhibitors were compared with placebo in 45 studies (n = 11 232) and with active comparators in 13 studies (n = 5175). They had a favorable effect on hemoglobin A1c level (mean difference vs. placebo, -0.66% [95% CI, -0.73% to -0.58%]; mean difference vs. active comparators, -0.06% [CI, -0.18% to 0.05%]). Sensitivity analyses incorporating unpublished data showed similar effect estimates. Compared with other agents, SGLT2 inhibitors reduced body weight (mean difference, -1.80 kg [CI, -3.50 to -0.11 kg]) and systolic blood pressure (mean difference, -4.45 mm Hg [CI, -5.73 to -3.18 mm Hg]). Urinary and genital tract infections were more common with SGLT2 inhibitors (odds ratios, 1.42 [CI, 1.06 to 1.90] and 5.06 [CI, 3.44 to 7.45], respectively). Hypoglycemic risk was similar to that of other agents. Results for cardiovascular outcomes and death were inconclusive. An imbalance in incidence of bladder and breast cancer was noted with dapagliflozin compared with control. Most trials were rated as high risk of bias because of missing data and last-observation-carried-forward methods. Sodium-glucose cotransporter 2 inhibitors may improve short-term outcomes in adults with type 2 diabetes, but effects on long-term outcomes and safety are unclear. None.