Aim To assess the efficacy and safety of oral semaglutide, a novel glucagon‐like peptide‐1 receptor agonist, for patients with type 2 diabetes. Methods We searched Medline, Embase, the Cochrane Library and grey literature sources up to July 1, 2019 for randomized controlled trials (RCTs) comparing oral semaglutide with placebo or other antidiabetic agents. The primary outcome was change from baseline in HbA1c. Secondary outcomes included change from baseline in body weight and blood pressure, cardiovascular endpoints, severe hypoglycaemia, gastrointestinal adverse events and diabetic retinopathy. We synthesized results using weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes, along with 95% confidence intervals (CIs). Results We included 11 RCTs with 9890 patients in the systematic review. Compared with placebo, oral semaglutide reduced HbA1c and body weight (WMD –0.89%, 95% CI −1.07 to −0.71 and − 2.99 kg, 95% CI −3.69 to −2.30, respectively). Oral semaglutide was also superior to other active comparators (including liraglutide, empagliflozin and sitaglipitin) in terms of lowering HbA1c (WMD –0.35%, 95% CI −0.43 to −0.26) and reduction of body weight (WMD −1.48 kg, 95% CI −2.28 to −0.67), and had a favourable effect on systolic blood pressure. Compared with placebo, oral semaglutide reduced all‐cause mortality (OR 0.58, 95% CI 0.37 to 0.92) and cardiovascular mortality (OR 0.55, 95% CI 0.31 to 0.98), and had a neutral effect on myocardial infarction, stroke, severe hypoglycaemia and diabetic retinopathy. However, treatment with oral semaglutide increased the incidence of nausea, vomiting and diarrhea, while events of acute pancreatitis were rare. Conclusions Oral semaglutide can effectively and safely reduce blood glucose, body weight and systolic blood pressure. Nevertheless, it is associated with increased incidence of gastrointestinal adverse events. Further research is needed to clarify its long‐term safety and comparative effectiveness against other antidiabetic agents.

Aim To assess the efficacy and safety of glucose‐lowering drugs used as an adjunct to insulin therapy in adults with type 1 diabetes. Methods We searched Medline, Embase and the Cochrane Central Register of Controlled Trials up to 24 January 2020 for randomized controlled trials. Our primary outcome was change in HbA1c. We additionally assessed eight efficacy and six safety secondary endpoints. We performed random effects frequentist network meta‐analysis to estimate mean differences (MDs) and odds ratios (ORs), alongside 95% confidence intervals (CIs). We assessed risk of bias and evaluated confidence in the evidence for the primary outcome. Results We included 58 trials comprising 13 216 participants. Overall, sodium‐glucose co‐transporter (SGLT) inhibitors, liraglutide, glibenclamide, acarbose and metformin reduced HbA1c compared with placebo (MDs ranging from −0.46% [95% CI −0.64% to −0.29%] for empagliflozin to −0.20% [−0.35% to −0.06%] for metformin). SGLT inhibitors, exenatide daily, liraglutide and metformin reduced body weight and total daily insulin dose, while liraglutide and SGLT inhibitors reduced blood pressure. Diabetic ketoacidosis and genital infections were more frequent with SGLT inhibitors, while exenatide, liraglutide, pramlintide and metformin increased the incidence of nausea. No drug increased the incidence of severe hypoglycaemia. Confidence in evidence was mainly moderate to very low. Conclusions Specific drugs may improve glycaemic control and reduce body weight, blood pressure and total daily insulin dose in patients with type 1 diabetes. However, low quality of evidence and an increased risk of diabetic ketoacidosis, genital infections or gastrointestinal adverse events should be taken into consideration by healthcare providers and patients. Future long‐term trials are needed to clarify their benefit‐to‐risk profile and elucidate their role in clinical practice.

Aim: To assess the efficacy and safety of sotagliflozin in patients with type 2 diabetes.Methods: We searched Medline, Embase, the Cochrane Library, and grey literature sources up to August 2021 for randomized controlled trials (RCTs) that compared sotagliflozin with placebo or other antidiabetic agents in patients with type 2 diabetes. Our primary outcome was change in HbA1c from baseline. We additionally assessed three secondary efficacy and 15 safety outcomes. We synthesized data using weighted mean differences (WMDs) and odds ratios (ORs), along with 95% confidence intervals (CIs).Results: We included 11 RCTs comprising 16 411 subjects in the meta-analysis. Compared with placebo, sotagliflozin reduced HbA1c (WMD À0.42%, 95% CI À0.56 to À0.29), body weight (WMD À1.33 kg, 95% CI À1.57 to À1.09), and systolic blood pressure (WMD À2.44 mmHg, 95% CI À2.81 to À2.07). No difference was evident against other active comparators. Sotagliflozin reduced myocardial infarction (OR 0.72, 95% CI 0.54 to 0.97) and heart failure (OR 0.68, 95% CI 0.58 to 0.79) compared with placebo, and had a neutral effect on all-cause mortality, cardiovascular mortality, and stroke.Treatment with sotagliflozin was safe regarding the incidence of serious adverse events, hypoglycaemia, and diabetic ketoacidosis. Nevertheless, it was associated with an increased incidence of diarrhoea, genital infections, and volume depletion events.Conclusions: Sotagliflozin reduces blood glucose, body weight, and systolic blood pressure, and demonstrates a beneficial effect on heart failure and myocardial infarction. Its overall safety profile is comparable with other sodium-glucose cotransporter-2 inhibitors.

We performed a systematic review and meta‐analysis of randomized controlled trials to assess the efficacy and safety of the novel, ultra‐rapid‐acting insulins aspart and lispro in adults with type 1 or type 2 diabetes. Our primary outcome was change in HbA1c from baseline. We additionally assessed eight efficacy and six safety endpoints. We calculated weighted mean differences (WMD) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes, alongside 95% confidence intervals (CIs). We additionally assessed statistical heterogeneity among studies with the I2 statistic, considering values greater than 60% as indicative of substantial heterogeneity. Nine studies comprising 5931 patients were included in the systematic review; eight active‐controlled studies could be synthesized in terms of a meta‐analysis. Treatment with ultra‐rapid‐acting insulins had a similar effect on change in HbA1c compared with rapid‐acting insulins (WMD −0.02%, 95% CI −0.08 to 0.05, I2 = 61% for patients with type 1 diabetes and −0.02%, 95% CI −0.09 to 0.04, I2 = 19% for patients with type 2 diabetes). Similarly, no difference was evident in terms of change in fasting plasma glucose, self‐measured plasma glucose, body weight, basal or bolus insulin dose, incidence of serious adverse events and hypoglycaemia. Compared with rapid‐acting insulins, ultra‐rapid‐acting insulins reduced 1‐ and 2‐hour postprandial glucose (PPG) increment based on a liquid meal test, both in patients with type 1 and type 2 diabetes (WMD −0.94 mmol/L, 95% CI −1.17 to −0.72, I2 = 0% and −0.56 mmol/L, 95% CI −0.79 to −0.32, I2 = 0%, respectively, for change in 1‐hour PPG increment). In conclusion, ultra‐rapid‐acting insulins were as efficacious and safe as rapid‐acting insulins, showing a favourable effect solely on PPG control.

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BackgroundPulmonary fibrosis is one of the gravest manifestations of Systemic Sclerosis (SSc) and conventional DMARDs therapy has not shown any particular positive effect.ObjectivesOur goal was to see whether the elimination pf B - lymphocytes through use of anti – CD20 Mab, Rituximab (RTX) would offer to the improvement of the pulmonary function of SSc patients.MethodsWe studied 23 SSc patients with pulmonary fibrosis, who received treatment with RTX (n=12) or DMARDs treatment (n=11) for 1 to 3 years (1,9 years). Conventional therapy included azathioprine (n=4), mycophenalate (n=6) and methotrexate (n=2). RTX – treated patients were recorded with FVC improvement in the first year of treatment (FVC 81,3 +/- 12,6 vs FVC 87,4 +/- 11,3 out on the onset of the study and at the first year respectively, p=0,02) when on the other hand DMARDs treated patients didn't show any FVC improvement at all.ResultsAll RTX – treated patients did not present any lung HRCT deterioration imaging, in contrast to DMARDs – treated patients who were also submitted to lung HRCT each year of the study, all showing signs of CT imaging deterioration. Similar findings, as far as FVC was concerned, were recorded at the 3rd year of the study (RTX patients, n=6 and DMARDs patients, n=11). 3rd year RTX FVC was 92,6 +/-13,2 vs 80,7 +/-11,8 at the onset of the study, p=0,04 when DMARDs treated patients were all presented with worst 3rd year FVC compared to their primary FVC, p<0,01.ConclusionsOur small cohort of SSc patients with pulmonary fibrosis shows that it is possible that rituximab may be proven helpful to at least prevent the deterioration of the interstitial pulmonary fibrosis of Systemic Sclerosis. The pathophysiology of this particular fibrosis and the possible molecular role of B-lymphocytes in the inversion of this procedure need yet to be furtherly explored.Disclosure of InterestNone declared

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) constitute a drug class primarily developed for the treatment of subjects with type 2 diabetes, although they have also provided significant benefit for subjects with obesity without underlying diabetes. Individuals with psychotic disorders who are receiving antipsychotic treatment are a patient population at risk of developing obesity, which is linked to other metabolic disturbances. Methods: We searched PubMed and the Cochrane Library from inception to 1 December 2022, for randomized controlled trials (RCTs) enrolling obese or overweight adult subjects with an underlying psychotic disorder treated with antipsychotic drugs, randomized either to GLP-1RAs or a control. We set as the primary efficacy outcome the change in body weight and as secondary efficacy outcomes the change in body mass index (BMI) and in waist circumference, along with indices of glycemia, lipid profile, and blood pressure. Results: We pooled data from 4 trials (2 with liraglutide and 2 with exenatide) in a total of 199 enrolled subjects. GLP-1RA treatment, compared to control, resulted in a significant decrease in body weight by 3.8 kg [mean difference (MD) = −3.80, 95% CI; −6.35 to −1.24, I2 = 64%]. In addition, GLP-1RA treatment led to a significant decrease in BMI, compared to control, of 1.04 kg/m2 (MD = −1.04, 95% CI; −1.92 to −0.17, I2 = 35%). However, no significant effect on waist circumference was shown (MD = −3.2, 95% CI; −6.47 to 0.08, I2 = 88%). A significant improvement in glycemia and lipid profiles was also demonstrated with GLP-1RAs. No subgroup difference between liraglutide and exenatide was shown, and the use of GLP-1RAs did not increase the risk for treatment discontinuation compared to the control group. Conclusion: Treatment with GLP-1RAs can significantly improve weight loss and other cardiometabolic risk factors in obese people taking antipsychotic medications.

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