Research Studies

This trial is conducted in Europe. The aim of the trial is to investigate the effects of semaglutide on ß-cell function in subjects with type 2 diabetes.

This trial is conducted in China. The aim of the trial is to evaluate the efficacy and safety of BGM0504 versus semaglutide as add-on to metformin and/or sulfonylureas in patients with type 2 diabetes

This trial is conducted in Africa, Asia, Europe, North and South America. The aim of the trial is to compare the effect of once-weekly (OW) dosing of subcutaneous semaglutide (1.0 mg) versus once-daily dosing of oral canagliflozin (300 mg) on glycaemic control in subjects with type 2 diabetes (T2D) on a background treatment of metformin

This study is designed to determine whether therapy with once-weekly sc semaglutide in combination with once-daily insulin degludec will be capable of maintaining (or improving) glycemic control, when substituted for multiple daily injections of insulin (MDI), in patients with T2D with adequate glycemic control (≤ 7.5%) on MDI-based regimens (≤ 80 units of insulin per day), vs. further titration of insulin therapy in those continuing MDI. Weight loss, hypoglycemic episodes, and improvement in diabetes-treatment satisfaction will also be assessed between the two groups. Patients with type-2 diabetes mellitus (T2D) are often overweight or obese. In order to obtain adequate glycemic control, many of these patients require intensive therapy with multiple daily injections of insulin (referred to as MDI, basal/bolus regimen), using a rapid-acting/bolus insulin at each meal in combination with a once- or twice-daily long- acting/basal insulin. Unfortunately, intensive insulin therapy can result in undesired weight gain, which may, in part, result in further insulin resistance. In addition, weight gain may adversely affect the control of comorbid health conditions (hypertension, hyperlipidemia, congestive heart failure, sleep apnea, etc.). The burden of disease management with multiple daily injections of insulin also serves as a barrier to A1C goal attainment as maintaining compliance with such complex regimens is often challenging in the real-world setting. Once patients with T2D require multiple daily injections of insulin to obtain glycemic control, it is generally considered to be a permanent/life-long therapy. However, reports have demonstrated the safety and effectiveness of adding once-daily glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide to basal insulin therapy in order to obtain glycemic control (1, 2), and in clinical practice, the addition of liraglutide (or other FDA-approved GLP-1RAs) to basal insulin often negates or delays the need to initiate prandial insulin. Subsequently, a newer form of anti-diabetic therapy, a once-daily injectable combination of GLP-1RA and basal insulin, became available and demonstrated promise that perhaps glycemic control may even be obtained with less complex regimens (i.e., less daily injections). There are currently two GLP-1RA/basal insulin combination therapies that are FDA approved: iGlarLixi (Soliqua®), and iDegLira (Xultophy®) (3, 4). While these observations with iGlarLixi and iDegLira demonstrating an improvement in A1C while avoiding prandial insulin injections are very exciting, what remains unclear is if patients with reasonable glycemic control (A1C ≤ 7.5%) currently receiving MDI (basal/bolus, 3-4 injections per day) could potentially maintain or even improve glycemic control by switching to a once-daily injectable product like Xultophy® or Soliqua®. Currently, there are no studies available (or planned) that have answered this clinical question. One limitation of these combination products in the clinical setting is the inability to independently titrate the GLP-1RA and basal insulin components. If a patient begins to experience hypoglycemia, and/or their fasting BG values are currently within the goal range, the dose of these combination products cannot be further titrated, limiting one's ability to further improve glycemic control in patients with a residual A1C elevation. What also remains unclear is if some of the newer formulations of GLP-1RA may also be able to reduce the burden of disease management and maintain glycemic control in patients who are currently well-controlled on a regimen of MDI. Recently, subcutaneous (sc) once-weekly semaglutide has been demonstrated to be capable of improving glycemic control in patients with T2D in combination with insulin therapy. In SUSTAIN-5 (5), at week 30, subcutaneous semaglutide 0.5 and 1.0 mg was demonstrated to reduce A1C by 1.4% and 1.8%, respectively, vs 0.1% with placebo \[mean baseline A1C value, 8.4%\] in a population of T2D patients receiving stable therapy with basal insulin with or without metformin. Moreover, mean body weight (kg) decreased with semaglutide 0.5 and 1.0 mg vs placebo from baseline to end of treatment: 3.7, 6.4, and 1.4 kg, respectively. Premature treatment discontinuation due to adverse events was higher for semaglutide 0.5 and 1.0 mg vs placebo (4.5%, 6.1%, and 0.8%), mainly due to gastrointestinal disorders. Even if the transition from MDI to once-daily sc semaglutide in combination with basal insulin were successful in only a minority of patients, the clinical advantage and reduction in burden of disease management that would be associated with transitioning from 3-4 injections of insulin per day to a regimen of once- weekly sc semaglutide and a once-daily injection of basal insulin would be a rather dramatic and remarkable transformation for patients, and one that would likely improve patients' diabetes treatment satisfaction. It would also help to solidify the effectiveness and safety of semaglutide in yet another population of patients with T2D. What cannot be minimized is the tremendous impact that a successful transition to once-weekly semaglutide and once-daily basal insulin could have on patients in terms of reducing their insulin requirements, assisting with weight loss (or mitigating further weight gain), and reducing the frequency and burden of hypoglycemia. In my clinical experience, once patients are titrated to full dose GLP-1RA therapy and attain adequate glycemic control, insulin doses (particularly prandial insulin) can often be further reduced or eliminated without negatively impacting glycemic control. Continuing the insulin therapy at higher doses in these patients simply suppresses the glucose-dependent secretion of endogenous insulin being promoted by the GLP-1RA therapy. Often, only an abrupt cessation of prandial insulin, or a step-wise down-titration of insulin therapy in these patients, will reveal that insulin therapy is no longer required at higher doses to maintain glycemic control. When this does successfully occur, the impact on patients is transformational. The purpose of this study is to investigate the ability of once-weekly sc semaglutide (in combination with once-daily basal insulin) to maintain or improve glycemic control in patients currently receiving MDI, while providing the patients with a significant reduction in the burden of disease management. In addition, this approach may also furnish a positive effect on weight management, a reduction in hypoglycemic episodes, and improvement in diabetes treatment satisfaction, when substituted for basal/bolus therapy in patients with T2D who currently have adequate glycemic control (A1C ≤ 7.5%) with a regimen of MDI (requiring a total of ≤ 80 units of insulin per day). The A1C cut-point of ≤ 7.5% was chosen because many patients on complex treatment regimens (MDI) with reasonable control, i.e., 7-7.5%, would be expected to have a realistic chance of success by switching from MDI to sc semaglutide and basal insulin combination therapy. Also, many patients taking complex insulin regimens (MDI) fall in the close to A1C goal range of 7-7.5%, so using this cut-point, vs. \< 7%, would make recruitment easier. Lastly, patients receiving MDI who are older and/or with heart disease also have higher individual A1C goal/targets around 7.5%. This study will also assess the impact that a successful substitution may have on the patients' diabetes treatment satisfaction, an important, yet under-appreciated aspect of diabetes management.

Post-operative administration of ipamorelin is expected to reduce time to recovery of Gastrointestinal (GI) function in patients who have undergone partial small and/or large bowel resection.

Efficacy and safety of Thymalfasin adjuvant therapy in HBV-related HCC after curative resection. Multi-center, Randomized, Controlled Clinical Trial to Evaluate the Efficacy and Safety of Adjuvant Thymalfasin Therapy in Hepatitis B Virus (HBV)-Related Hepatocellular Carcinoma After Curative Resection.

The purpose of this research study is to determine the safety and tolerability of up to five doses of VRS-317 in Adult Growth Hormone Deficient patients. * Patients will be evaluated for evidence of activity of VRS-317 by measurement of changes from baseline in insulin-like growth factor-1 (IGF-I) and binding protein (IGFBP-3), and bone turnover (bone alkaline phosphatase) * Descriptive pharmacokinetic (PK) and pharmacodynamic (PD) parameters (IGF-I and IGFBP-3) will be determined by standard model independent methods based on the plasma concentration-time data of each subject. These parameters include: Cmax, Tmax, AUCavg, AUC0-inf, and t1/2. * The purpose is to determine the appropriate dose of VRS-317 to maintain a normal range (for appropriate age/gender) for IGF-I levels in adult patients for up to one month after administration of a single dose The study is a placebo controlled single ascending dose (SAD) study in adult GHD patients currently receiving daily rhGH therapy. After screening patients are withdrawn from daily rhGH therapy for a minimum of 7 days (maximum of 60 days) prior to randomization for treatment. Patients will be randomised within a treatment group that is currently being enrolled once the patient has passed the pre-dose screening criteria. Documented confirmation (medical history) of GHD during adulthood by a minimum of one or more GH stimulation tests is required such as: * insulin tolerance test (ITT; peak hGH ≤ 5.0 ng/mL), * arginine alone (peak hGH ≤ 0.4 ng/mL); * arginine + growth-hormone-releasing hormone\* (see below); * or glucagon stimulation test (peak hGH ≤ 3.0 ng/mL) OR * at least 3 other pituitary hormone deficiencies and a low IGF-I for age/gender appropriate normal range Each patient will be randomised to receive either the investigational product, VRS-317 (Cohorts A-E), or placebo (Cohort F) in a 4:1 ratio. Subjects will be monitored for safety throughout their participation in the study. To ensure patient safety, two patients (1 active, 1 placebo) in the first treatment group, one from Cohort A and one from Cohort F1, will be dosed in a blinded manner and monitored for 48 hr prior to dosing the remaining 8 patients. The 8 remaining patients will be blinded and randomized to the first treatment group. Vital signs, clinical lab values, adverse events (AEs) and concomitant medications (CMs) will be captured. AEs will be graded using the Common Terminology Criteria for Adverse Events (CTCAE v 4.0)1, and the Primary Dermal Irritation Scoring Scale; AEs will be coded using the MedDRA2 dictionary and CMs using the WHO Drug dictionary. Prior to escalating to a higher dose level, safety data will be reviewed by the principal investigator (PI), co-PIs, the Sponsor, and the medical monitor for any potential safety risk to subjects. Patients will participate for a total of 83-215 days. A 7-60 day withdrawal phase (no daily rhGH therapy) is followed by receiving assigned doses on Day 1 of Treatment Phase, PK/PD and safety assessments for 30 days, and an additional 30 days of follow up. Safety evaulations will be performed to assess safety including but not limited to: * Physical examination * Vital signs (including sitting/supine blood pressure) * Laboratory tests: hematology, chemistry, urinalysis, and pregnancy testing (in women of child-bearing age) * Adverse events and concomitant medications * Glucose metabolism: Fasting and post-prandial plasma glucose and fasting insulin pre-study and at pre-scheduled timepoints during the study (per Assessment Table) * Lipid profile will be assessed pre-study and at pre-scheduled timepoints during the study (per Assessment Table) * Assessment for adrenal insufficiency prior to enrollment and at Day 30 (not performed on patients with documented history of adrenal insufficiency) * Evaluation of injection site reactions * Anti-VRS-317 antibody assay (pre-dose, Day 30 (end of study) and Day 60) last follow up visit * Safety monitoring will continue for up to 60 days post-dose

Premixed insulin-based therapy is a standard insulin treatment strategy in Austria. The widespread use of premixed insulin is explained by high acceptance by health care professionals and patients due to one single product and flexible number of injections (1-3 daily) which covers the demand in controlling fasting and postprandial glucose excursions of most patients with diabetes. However, the use of pre-mixed insulin frequently leads to a high insulin demand and consequently weight gain and an increased risk of hypoglycemia. Hence, achieve good metabolic control in these patients remains a major challenge. For those patients, the approach to treatment intensification without facing the typical risks of insulin treatment (hypoglycemia and weight increase) is of major importance. One, so far not exploited option may be the BIT-strategy: Basal insulin in combination with incretin-based therapy. Pathophysiologically basal insulin inhibits glucose production in the liver, decreases hepatic insulin resistance and improves the function of beta cells in the postprandial state by discharge of fasting insulin secretion. During further diabetes progression steadily increasing HbA1c levels - despite good fasting blood glucose control - indicate the need for additional intervention of meal-related glucose excursions. In this stage of type-2 diabetes basal insulin can be combined with prandial (short-acting) insulin or prandial GLP-1 receptor agonists. However, regarding important safety parameters: risks of hypoglycemia and weight gain in the long-term treatment GLP-1 receptor agonists are beneficial. Lixisenatide is a novel GLP-1 receptor agonist with a pronounced postprandial (PPG) effect which fits with basal insulin mode of action primarily focused on fasting blood glucose reduction. Therefore 10 patients (both gender) under treatment with premixed insulin (2-3 times daily) and HbA1c\>7% will be switched to basal insulin glargine (Lantus, once daily) and GLP-1 receptor agonist Lixisenatide (Lyxumia, once daily). The investigators hypothesize that switching from a therapy based on premixed insulin to a simple, once daily administered combination of basal insulin plus a GLP-1 receptor agonist in patients with type-2 diabetes not achieving therapeutic target (HbA1c\>7%) is clinically feasable in an out patient setting

Obesity is a disease not always attributable to nutritional imbalance, frequently associated with changes in key hypothalamic-pituitary (HP) axes. The regain of weight loss after hypochaloric diets has been ascribed to these HP disregulations. The aim of the study is to explore pituitary morphology and its association with pituitary function and metabolic phenotype in outpatient obese individuals evaluated in the period 2010-2013 at the Department of Experimental Medicine of the University of Rome La Sapienza, with features of HP disease in a cross-sectional .