Gastrointestinal tolerability and weight reduction associated with tirzepatide in adults with obesity or overweight with and without type 2 diabetes in the SURMOUNT-1 to -4 trials.

Aims: This analysis evaluated whether gastrointestinal (GI) adverse events (AEs) including nausea, vomiting, diarrhoea (N/V/D) and dyspepsia were associated with weight reduction with tirzepatide across the SURMOUNT-1 to -4 trials.

Materials And Methods: SURMOUNT-1 to -4 were global Phase 3 clinical trials evaluating the safety and efficacy of tirzepatide among participants with obesity or overweight with or without type 2 diabetes (T2D). Participants were randomly assigned to receive once weekly subcutaneous tirzepatide or placebo.

Survodutide for treatment of obesity: rationale and design of two randomized phase 3 clinical trials (SYNCHRONIZE™-1 and -2).

Objective: The objective of this study was to describe the rationale and design of two multinational phase 3 clinical trials of survodutide, an investigational glucagon and glucagon-like peptide-1 receptor dual agonist for the treatment of obesity with or without type 2 diabetes (T2D; SYNCHRONIZE-1 and -2).

Methods: In these ongoing double-blind trials, participants were randomized to once-weekly subcutaneous injections of survodutide or placebo added to lifestyle modification. Survodutide doses are uptitrated to 3.

Efficacy and safety of once-weekly semaglutide 2·4 mg versus placebo in people with obesity and prediabetes (STEP 10): a randomised, double-blind, placebo-controlled, multicentre phase 3 trial.

Background: There are currently limited data regarding the effect of semaglutide 2·4 mg in individuals with obesity and prediabetes in clinical trials. We aimed to assess the efficacy and safety of semaglutide 2·4 mg for weight management and glycaemic control in participants with obesity and prediabetes.

Methods: STEP 10 was a randomised, double-blind, parallel-group, phase 3 trial done across 30 trial sites in Canada, Denmark, Finland, Spain, and the UK and included participants aged 18 years or older with a BMI of 30 kg/m or higher and prediabetes according to UK National Institute for Health and Care Excellence criteria (defined as having at least one of the following at screening: HbA of 6·0-6·4% [42-47 mmol/mol] or fasting plasma glucose [FPG] of 5·5-6·9 mmol/L).

Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high-dose GLP-1 receptor agonists and GLP-1 receptor-based co-agonists.

Type 2 diabetes (T2D), obesity, and nonalcoholic fatty liver disease/nonalacoholic steatohepatitis (NAFLD/NASH) share mutual causalities. Medications that may offer clinical benefits to all three conditions are being developed. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for the management of T2D and obesity and there is great interest in evaluating higher doses of available GLP-1RAs and developing novel GLP-1RA-based co-agonists to provide greater reductions in glycated hemoglobin (HbA1c) and body weight as well as modifying NAFLD/NASH complications in clinically meaningful ways.

Efficacy and safety of once-daily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS): a multicentre, randomised, phase 3b trial.

Background: Once-daily oral semaglutide is an effective type 2 diabetes treatment. We aimed to investigate a new formulation of oral semaglutide at higher investigational doses versus the approved 14 mg dose in adults with inadequately controlled type 2 diabetes.

Methods: This global, multicentre, randomised, double-blind, phase 3b trial, carried out at 177 sites in 14 countries, enrolled adults with type 2 diabetes, glycated haemoglobin (HbA) 8·0-10·5% (64-91 mmol/mol), a BMI of 25·0 kg/m or greater, receiving stable daily doses of one to three oral glucose-lowering drugs.

Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial.

Background: Combining the GLP-1 receptor agonist semaglutide with the long-acting amylin analogue cagrilintide has weight-loss benefits; the impact on glycated haemoglobin (HbA) is unknown. This trial assessed the efficacy and safety of co-administered semaglutide with cagrilintide (CagriSema) in participants with type 2 diabetes.

Methods: This 32-week, multicentre, double-blind, phase 2 trial was conducted across 17 sites in the USA.

Relationship between body weight change and glycaemic control with tirzepatide treatment in people with type 2 diabetes: A post hoc assessment of the SURPASS clinical trial programme.

Aim: To assess the relationship between HbA1c and body weight reductions with tirzepatide treatment (5, 10 or 15 mg).

Materials And Methods: HbA1c and body weight data at 40 weeks (SURPASS-1, -2 and -5) and 52 weeks (SURPASS-3 and -4) were analysed by trial.

Results: Across the SURPASS clinical trials, HbA1c reductions from baseline were observed in 96%-99%, 98%-99% and 94%-99% of participants treated with tirzepatide 5, 10 and 15 mg, respectively.

A Cross-sectional Survey to Assess Reasons for Therapeutic Inertia in People With Type 2 Diabetes Mellitus and Preferred Strategies to Overcome It From the Perspectives of Persons With Diabetes and General/Family Practitioners: Results From the MOTION Study.

Objectives: Although multiple causes of therapeutic inertia in type 2 diabetes mellitus (T2DM) have been identified, few studies have addressed the behavioural aspects of treatment-intensification decisions among persons with type 2 diabetes (PwT2DM) and general practitioners/family practitioners (GPFPs).

Methods: A quantitative online survey was developed to capture from 300 PwT2DM and 100 GPFPs the following information: 1) perspectives on shared decision-making (SDM) related to treatment intensification, using the 9-item Shared Decision Making Questionnaire and the Shared Decision Making Questionnaire---physician version; 2) intentions to intensify treatments, using the Theory of Planned Behaviour (TPB); and 3) preferred strategies to overcome causes of therapeutic inertia in T2DM. Regression methods were applied post hoc to examine correlations with SDM scores, behavioural intentions and behaviours.

Persons With Diabetes and General/Family Practitioner Perspectives Related to Therapeutic Inertia in Type 2 Diabetes Mellitus Using Qualitative Focus Groups and the Theoretical Domains Framework: Results From the MOTION Study.

Objectives: Therapeutic inertia in type 2 diabetes (T2DM) is the failure to receive timely treatment intensification as indicated according to T2DM treatment guidelines. Multifactorial causes of therapeutic inertia in T2DM have been documented at the level of persons with diabetes (PwD), health-care providers and health-care systems.

Methods: We developed a 3-part mixed-methods research program, called the Moving to Overcome Therapeutic Inertia Obstacles Now in T2DM (MOTION) study, to inform the development of strategies to address therapeutic inertia in T2DM.

Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial.

Background: Natural amylin is a pancreatic hormone that induces satiety. Cagrilintide is a long-acting amylin analogue under investigation for weight management. We assessed the dose-response relationship of cagrilintide regarding the effects on bodyweight, safety, and tolerability.

Managing the gastrointestinal side effects of GLP-1 receptor agonists in obesity: recommendations for clinical practice.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are well established in clinical practice for the treatment of type 2 diabetes, and are approved and recommended for weight management in overweight or obesity. Gastrointestinal side effects are well known as the most common adverse effects of these agents and represent a potential barrier for use, particularly at higher doses. Drawing on both published evidence and our collective clinical experience, we aim to guide practitioners through managing these side effects with a view to optimizing therapeutic outcomes with GLP-1RAs.

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.

The role of icosapent ethyl in cardiovascular risk reduction.

Purpose Of Review: Elevated levels of triglycerides, independent of low-density lipoprotein cholesterol (LDL-C) levels and statin therapy, are associated with heightened cardiovascular risk.

Recent Findings: Mixed omega-3 fatty acid formulations, which contain varying amounts of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), lower triglycerides levels but trial results with omega-3 fatty acids combinations have generally been neutral for cardiovascular outcomes. In contrast, the REDUCE-IT trial with icosapent ethyl (IPE), a highly purified ethyl ester of EPA, demonstrated reduced cardiovascular risk in individuals with established atherosclerotic cardiovascular disease or diabetes with at least one additional risk factor, despite having relatively well controlled LDL-C levels but triglycerides at least 135 mg/dl while on statin therapy.

Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial.

Background: This trial assessed the efficacy and safety of the GLP-1 analogue once a week subcutaneous semaglutide 2·4 mg versus semaglutide 1·0 mg (the dose approved for diabetes treatment) and placebo for weight management in adults with overweight or obesity, and type 2 diabetes.

Methods: This double-blind, double-dummy, phase 3, superiority study enrolled adults with a body-mass index of at least 27 kg/m and glycated haemoglobin 7-10% (53-86 mmol/mol) who had been diagnosed with type 2 diabetes at least 180 days before screening. Patients were recruited from 149 outpatient clinics in 12 countries across Europe, North America, South America, the Middle East, South Africa, and Asia.

Efficacy and Safety of Liraglutide 3.0 mg in Individuals With Overweight or Obesity and Type 2 Diabetes Treated With Basal Insulin: The SCALE Insulin Randomized Controlled Trial.

Objective: Most individuals with type 2 diabetes also have obesity, and treatment with some diabetes medications, including insulin, can cause further weight gain. No approved chronic weight management medications have been prospectively investigated in individuals with overweight or obesity and insulin-treated type 2 diabetes. The primary objective of this study was to assess the effect of liraglutide 3.

Perceptions of barriers to effective obesity management in Canada: Results from the ACTION study.

Obesity is a chronic disease with a significant and growing impact on Canadians. The "Awareness, Care and Treatment In Obesity MaNagement" (ACTION) Study investigated perceptions, attitudes and perceived barriers to obesity management among Canadian people with obesity (PwO), healthcare providers (HCPs) and employers. In this study adult PwO (body mass index ≥30 kg/m , based on self-reported height/weight), HCPs (physicians and allied HCPs managing PwO) and employers (≥20 employees; offering health insurance), completed online surveys between 3 August and 11 October 2017 in a cross-sectional design.

Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.

Background: Establishing cardiovascular safety of new therapies for type 2 diabetes is important. Safety data are available for the subcutaneous form of the glucagon-like peptide-1 receptor agonist semaglutide but are needed for oral semaglutide.

Methods: We assessed cardiovascular outcomes of once-daily oral semaglutide in an event-driven, randomized, double-blind, placebo-controlled trial involving patients at high cardiovascular risk (age of ≥50 years with established cardiovascular or chronic kidney disease, or age of ≥60 years with cardiovascular risk factors only).

Cardiovascular safety of oral semaglutide in patients with type 2 diabetes: Rationale, design and patient baseline characteristics for the PIONEER 6 trial.

Aims: To assess the cardiovascular (CV) safety of oral semaglutide, the first tablet formulation of a glucagon-like peptide-1 receptor agonist.

Materials And Methods: PIONEER 6 is a multinational, randomized, placebo-controlled, double-blind trial in patients with type 2 diabetes at high risk of CV events (defined as being aged ≥50 years and having established CV disease [CVD] or moderate [stage 3] chronic kidney disease [CKD], or being aged ≥60 years with ≥1 other CV risk factor). Patients were randomized to once-daily oral semaglutide (up to 14 mg) or placebo added to standard of care.

Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial.

Background: Obesity is a major public health issue, and new pharmaceuticals for weight management are needed. Therefore, we evaluated the efficacy and safety of the glucagon-like peptide-1 (GLP-1) analogue semaglutide in comparison with liraglutide and a placebo in promoting weight loss.

Methods: We did a randomised, double-blind, placebo and active controlled, multicentre, dose-ranging, phase 2 trial.

Family Intervention for Obese/Overweight Children Using Portion Control Strategy (FOCUS) for Weight Control: A Randomized Controlled Trial.

Nutritional counseling for children with obesity is an important component of management. This randomized controlled trial was conducted to compare change in body mass index (BMI) score after 6 months. Children 8 to 16 years with a BMI greater than the 85th percentile were randomized to standard of care nutrition counseling versus intervention with standard nutrition counseling including portion control tool training for the family.

A weight-loss program adapted to the menstrual cycle increases weight loss in healthy, overweight, premenopausal women: a 6-mo randomized controlled trial.

Background: Hormonal fluctuations during the menstrual cycle influence energy intake and expenditure as well as eating preferences and behavior.

Objective: We examined the effect in healthy, overweight, premenopausal women of a diet and exercise weight-loss program that was designed to target and moderate the effects of the menstrual cycle compared with the effect of simple energy restriction.

Design: A total of 60 healthy, overweight, premenopausal women were included in a 6-mo weight-loss program in which each subject consumed a diet of 1600 kcal/d.