Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss.

Aim: We evaluated gastrointestinal (GI) adverse events (AEs) with once-weekly semaglutide 2.4 mg in adults with overweight or obesity and their contribution to weight loss (WL).

Materials And Methods: AE analyses pooled data from the Semaglutide Treatment Effect in People With Obesity (STEP) 1-3 trials for participants randomized to 68 weeks of semaglutide 2.

Glucose-dependent insulinotropic polypeptide induces lipolysis during stable basal insulin substitution and hyperglycaemia in men with type 1 diabetes: A randomized, double-blind, placebo-controlled, crossover clinical trial.

Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the glucose and lipid metabolism. We investigated the effects of exogenous GIP on lipid metabolism during time of stable insulin levels. Ten male patients with type 1 diabetes without endogenous insulin secretion (C-peptide-negative, mean [±SD] age 26 ± 4years, body mass index 24 [±2] kg/m , glycated haemoglobin 56 [±8] mmol/mol or 7.

Once-Weekly Semaglutide in Adults with Overweight or Obesity.

Background: Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed.

Semaglutide for the treatment of non-alcoholic steatohepatitis: Trial design and comparison of non-invasive biomarkers.

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease. There is a clear need to develop pharmacological treatment for patients with NASH as well as biomarkers that can diagnose the disease. We describe a trial of semaglutide treatment for NASH, identify key patient characteristics and compare the relationship of patient characteristics and non-invasive biomarkers/scores.

Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5.

Objective: The obesity epidemic is a public health concern, warranting further research into pharmacological treatments for weight management (WM) as an adjunct to lifestyle interventions. The Semaglutide Treatment Effect in People with obesity (STEP) program aims to investigate the effect of semaglutide versus placebo on weight loss, safety, and tolerability in adults with obesity or overweight.

Methods: Across five phase 3 trials (NCT03548935, WM; NCT03552757, WM in type 2 diabetes; NCT03611582, WM with intensive behavioral therapy; NCT03548987, sustained WM; and NCT03693430, long-term WM), ~5,000 participants are being randomly assigned to receive semaglutide 2.

Effect of semaglutide on liver enzymes and markers of inflammation in subjects with type 2 diabetes and/or obesity.

Background: Obesity and type 2 diabetes are drivers of non-alcoholic fatty liver disease (NAFLD). Glucagon-like peptide-1 analogues effectively treat obesity and type 2 diabetes and may offer potential for NAFLD treatment.

Aim: To evaluate the effect of the glucagon-like peptide-1 analogue, semaglutide, on alanine aminotransferase (ALT) and high-sensitivity C-reactive protein (hsCRP) in subjects at risk of NAFLD.

Hypoglycemia, Cardiovascular Outcomes, and Death: The LEADER Experience.

Objective: In the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) cardiovascular (CV) outcomes trial (NCT01179048), liraglutide significantly reduced the risk of CV events (by 13%) and hypoglycemia versus placebo. This post hoc analysis examines the associations between hypoglycemia and CV outcomes and death.

Research Design And Methods: Patients with type 2 diabetes and high risk for CV disease ( = 9,340) were randomized 1:1 to liraglutide or placebo, both in addition to standard treatment, and followed for 3.

Neoplasms Reported With Liraglutide or Placebo in People With Type 2 Diabetes: Results From the LEADER Randomized Trial.

Objective: This study explored neoplasm risk with liraglutide versus placebo in the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) cohort.

Research Design And Methods: LEADER (NCT01179048) was an international, phase 3b, randomized, double-blind, controlled trial. Participants aged ≥50 years with type 2 diabetes and high cardiovascular risk were assigned 1:1 to receive liraglutide (≤1.

Glucose-Dependent Insulinotropic Polypeptide (GIP) Inhibits Bone Resorption Independently of Insulin and Glycemia.

Context: The gut hormone glucose-dependent insulinotropic polypeptide (GIP) causes postprandial insulin release and inhibits bone resorption assessed by carboxy-terminal collagen crosslinks (CTX).

Objective: To study if GIP affects bone homeostasis biomarkers independently of insulin release and glycemic level.

Design: Randomized, double-blinded, crossover study with 5 study days.

Hepatic insulin resistance in NAFLD: relationship with markers of atherosclerosis and metabolic syndrome components.

Aims: Fat accumulation in the liver and in the muscle results in hepatic and muscle insulin resistance and has been associated with increased cardiovascular risk. It is unclear whether the individual role of hepatic and muscle insulin resistance in the onset of dyslipidaemia is observed in nonalcoholic fatty liver disease (NAFLD) patients and whether this association is mediated through traditional risk factors. The aim of this study was to assess hepatic and muscle insulin resistance in NAFLD and its relationship with carotid artery intima-media thickness (IMT) and the apoB/apoAI ratio as markers of atherosclerosis.

Glucose-dependent insulinotropic polypeptide augments glucagon responses to hypoglycemia in type 1 diabetes.

Glucose-dependent insulinotropic polypeptide (GIP) is glucagonotropic, and glucagon-like peptide-1 (GLP-1) is glucagonostatic. We studied the effects of GIP and GLP-1 on glucagon responses to insulin-induced hypoglycemia in patients with type 1 diabetes mellitus (T1DM). Ten male subjects with T1DM (C-peptide negative, age [mean ± SEM] 26 ± 1 years, BMI 24 ± 0.

Chronic exposure to GLP-1 increases GLP-1 synthesis and release in a pancreatic alpha cell line (α-TC1): evidence of a direct effect of GLP-1 on pancreatic alpha cells.

Aims/hypothesis: Incretin therapies, which are used to treat diabetic patients, cause a chronic supra-physiological increase in GLP-1 circulating levels. It is still unclear how the resulting high hormone concentrations may affect pancreatic alpha cells. The present study was designed to investigate the effects of chronic exposure to high GLP-1 levels on a cultured pancreatic alpha cell line.

Cardiovascular risk profile in subjects with prediabetes and new-onset type 2 diabetes identified by HbA(1c) according to American Diabetes Association criteria.

Objective: We investigated the cardiovascular risk profile in subjects with prediabetes and new-onset type 2 diabetes identified by glycated hemoglobin A1c (HbA(1c)) according to the new American Diabetes Association criteria.

Research Design And Methods: Arterial stiffness, intima-media thickness (IMT), soluble receptor for advanced glycation end products (sRAGEs), and oral glucose tolerance test (OGTT) were evaluated in 274 subjects without a previous history of diabetes. The subjects were stratified into three groups according to the HbA(1c) levels.

Alpha- and beta-cell abnormalities in haemoglobin A1c-defined prediabetes and type 2 diabetes.

New recommendations for the use of glycated haemoglobin A1c (HbA1c) to diagnose prediabetes and type 2 diabetes have changed the constitution of the two populations. We aimed to investigate the pathophysiological characteristics of individuals with HbA1c-defined prediabetes and type 2 diabetes, respectively. Ten subjects with HbA1c-defined prediabetes, i.

Glucose-dependent insulinotropic polypeptide: blood glucose stabilizing effects in patients with type 2 diabetes.

Context: Patients with type 2 diabetes mellitus (T2DM) have clinically relevant disturbances in the effects of the hormone glucose-dependent insulinotropic polypeptide (GIP).

Objective: We aimed to evaluate the importance of the prevailing plasma glucose levels for the effect of GIP on responses of glucagon and insulin and glucose disposal in patients with T2DM.

Design And Setting: We performed a single center, placebo-controlled, cross-over, experimental study.

Secretion of glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes: systematic review and meta-analysis of clinical studies.

Objective: To investigate glucose-dependent insulinotropic polypeptide (GIP) secretion in patients with type 2 diabetes and nondiabetic control subjects during oral glucose or meal tests.

Research Design And Methods: Eligible trials were identified by The Cochrane Library, MEDLINE, Embase, and Web of Science. Data were retrieved and random-effects models for the primary meta-analysis, random-effects meta-regression, and subgroup and regression analyses were applied.

Beta and alpha cell function in metabolically healthy but obese subjects: relationship with entero-insular axis.

Objective: Obesity is widely acknowledged as a critical risk factor for metabolic complications. Among obese subjects, there is a phenotype of metabolically healthy but obese (MHO) individuals that shows a favorable cardiometabolic risk profile. We aimed to evaluate the potential mechanisms underlying the metabolic profile of this subset, including alpha and beta cell function and entero-insular axis.

Elevated plasma glucose-dependent insulinotropic polypeptide associates with hyperinsulinemia in metabolic syndrome.

Background And Aims: Metabolic syndrome (MS) is a high-risk condition for type 2 diabetes, a disease characterized by insulin resistance and insulin secretion abnormalities. Insulin resistance has been widely characterized in MS subjects while insulin secretion has been poorly investigated. The present study was hence undertaken to further investigate the α and β cell function and entero-insular axis in this pre-diabetic condition.