Tirzepatide in Hispanic/Latino Patients With Type 2 Diabetes: A Subgroup Analysis of the SURPASS Program.

Context: Efficacy and safety of tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, have been studied in patients with type 2 diabetes in the global phase 3 SURPASS program.

Objective: This work aimed to assess the efficacy and safety of tirzepatide in Hispanic/Latino and non-Hispanic/Latino patients in SURPASS-1 to -4 clinical trials.

Methods: A total of 5679 patients were included, 2895 of self-reported Hispanic/Latino ethnicity, in this exploratory analysis of SURPASS-1 to -4 trial data.

Fixed-ratio Combinations (basal Insulin Plus GLP-1RA) In Type 2 Diabetes. an Analytical Review Of Pivotal Clinical Trials.

In type 2 diabetes, therapeutic failure to the oral anti diabetics is frequent, the use of schemes with basal insulin or with multiple doses of insulin (basal insulin and short-acting insulins) are a widely accepted way to intensify therapy. The use of GLP-1 receptor agonists is another intensification strategy. The fixedratio combinations with molecules such as insulin degludec + liraglutide, and insulin glargine + lixisenatide have proven useful in intensifying treatment of individuals with type 2 diabetes.

Efficacy and safety of once-weekly efpeglenatide in people with suboptimally controlled type 2 diabetes: The AMPLITUDE-D, AMPLITUDE-L and AMPLITUDE-S randomized controlled trials.

Aim: To evaluate the efficacy and safety of once-weekly (QW) efpeglenatide in people with type 2 diabetes (T2D) suboptimally controlled with oral glucose-lowering drugs and/or basal insulin (BI).

Materials And Methods: Three phase 3, multicentre, randomized controlled trials compared the efficacy and safety of QW efpeglenatide versus dulaglutide when added to metformin (AMPLITUDE-D), efpeglenatide versus placebo when added to BI ± oral glucose-lowering drugs (AMPLITUDE-L) or metformin ± sulphonylurea (AMPLITUDE-S). All trials were terminated early by the sponsor because of funding rather than safety or efficacy concerns.

An update on tirzepatide for the management of type 2 diabetes: a focus on the phase 3 clinical development program.

Introduction: Tirzepatide, a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA), received regulatory approval from the U.S. Food and Drug Administration (13 May 2022) and marketing authorization from the European Commission (25 September 2022) for the improvement of glycemic control in adults with type 2 diabetes (T2D).

Obesity among Latinx people in the United States: A review.

Obesity is a serious, chronic disease that is associated with a range of adiposity-based comorbidities, including cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver disease. In the United States, obesity is a public health crisis, affecting more than 40% of the population. Obesity disproportionately affects Latinx people, who have a higher prevalence of obesity and related comorbidities (such as cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver disease) compared with the general population.

Safety, pharmacokinetics, and pharmacodynamics of pegozafermin in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 1b/2a multiple-ascending-dose study.

Background: Management strategies for non-alcoholic steatohepatitis (NASH) are based predominantly on lifestyle modification, with no approved disease-modifying drugs yet available. We aimed to evaluate the safety, pharmacokinetics, and pharmacodynamics of pegozafermin (BIO89-100), a glycoPEGylated FGF21 analogue, in participants with NASH.

Methods: This randomised, double-blind, placebo-controlled, phase 1b/2a multiple-ascending-dose study enrolled adults (aged 21-75 years) who had NASH with stage F1-F3 fibrosis, or non-alcoholic fatty liver disease and a high risk of NASH (referred to in this study as phenotypic NASH) due to central obesity with type 2 diabetes, or central obesity with increased alanine aminotransferase (ALT) or a Fibroscan score of 7 kPa or greater, across 12 specialist centres and clinics in the USA.

Efficacy and Safety of Once-Weekly Efpeglenatide Monotherapy Versus Placebo in Type 2 Diabetes: The AMPLITUDE-M Randomized Controlled Trial.

Objective: To assess the efficacy and safety of the glucagon-like peptide 1 receptor agonist (GLP-1 RA) efpeglenatide versus placebo in patients with type 2 diabetes inadequately controlled with diet and exercise alone.

Research Design And Methods: AMPLITUDE-M was a phase 3, double-blind, placebo-controlled, multicenter trial that randomized adults with type 2 diabetes suboptimally controlled with diet and exercise alone to once-weekly efpeglenatide (2, 4, or 6 mg) or placebo for up to 56 weeks. The primary objective was to demonstrate the superiority of efpeglenatide versus placebo for HbA1c reduction at week 30.

Impact of disease duration and β-cell reserve on the efficacy of switching to iGlarLixi in adults with type 2 diabetes on glucagon-like peptide-1 receptor agonist therapy: Exploratory analyses from the LixiLan-G trial.

Aim: To evaluate the efficacy of iGlarLixi by C-peptide levels and duration of diabetes in an exploratory analysis of the LixiLan-G study.

Methods: LixiLan-G was a 26-week, randomized, open-label study in adults with type diabetes (T2D) inadequately controlled while on a glucagon-like peptide-1 receptor agonist (GLP-1 RA), with metformin, with or without pioglitazone and/or a sodium-glucose co-transporter-2 inhibitor. This analysis investigated the efficacy of switching to iGlarLixi by fasting baseline quartile C-peptide levels and baseline quartile of duration of T2D compared with continued GLP-1 RA use.

Efficacy and tolerability of tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes: A 12-week, randomized, double-blind, placebo-controlled study to evaluate different dose-escalation regimens.

Aim: To assess the efficacy and tolerability of tirzepatide treatment using three different dose-escalation regimens in patients with type 2 diabetes.

Materials And Methods: In this double-blind, placebo-controlled study, patients were randomized (1:1:1:1) to receive either once-weekly subcutaneous tirzepatide or placebo. The tirzepatide dose groups and dose-escalation regimens were: 12 mg (4 mg weeks 0-3; 8 mg weeks 4-7; 12 mg weeks 8-11), 15 mg-1 (2.

The SYDNEY Device Study: A Multicenter, Randomized, Open-label Usability Study of a 2-mL Alirocumab Autoinjector Device.

Purpose: The proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab has produced significant reductions in LDL-C at a dose of 300 mg q4w administered as 2 separate 150-mg injections via a 1-mL autoinjector (AI). A recently developed 2-mL device (SYDNEY) permits the administration of a single 300mg dose of alirocumab.

Methods: We assessed the usability and product technical complaints (PTCs) reported by patients using the 2-mL SYDNEY device in unsupervised settings, adverse events, and effects on LDL-C, in a multicenter, randomized, open-label, 16-week study conducted in the United States.

Clinical Characteristics and Glycemic Outcomes of Patients with Type 2 Diabetes Requiring Maximum Dose Insulin Glargine/Lixisenatide Fixed-Ratio Combination or Insulin Glargine in the LixiLan-L Trial.

Introduction: iGlarLixi is a titratable, fixed-ratio combination of insulin glargine (iGlar, 100 units/ml) and the glucagon-like peptide-1 receptor agonist lixisenatide for the treatment of patients with type 2 diabetes. This post hoc analysis of the phase 3 LixiLan-L trial (NCT02058160) investigated baseline characteristics, glycemic control, and safety outcomes in participants who received the study-specified maximum dose (60 units/day) of iGlarLixi or iGlar vs. those who received < 60 units/day.

Fixed-dose combination of ertugliflozin and metformin hydrochloride for the treatment of type 2 diabetes.

Combining antihyperglycemic agents in order to rapidly and safely achieve the best possible glycemic control is the standard of care today for the management of type 2 diabetes. Agents should ideally have mechanisms of actions that are complementary and that improve glycemic control without unacceptable gain in body weight or hypoglycemia. Areas covered: Ertugliflozin and metformin hydrochloride (ertugliflozin/metformin, SEGLUROMET) is a recently approved fixed-dose combination tablet containing the sodium-glucose co-transporter 2 (SGLT-2) inhibitor ertugliflozin and metformin.

Efficacy and safety of insulin glargine/lixisenatide (iGlarLixi) fixed-ratio combination in older adults with type 2 diabetes.

Aims: This study assessed the efficacy and safety of iGlarLixi (a titratable, fixed-ratio combination of insulin glargine [iGlar] plus lixisenatide) in older patients with type 2 diabetes.

Methods: This post hoc analysis used patient-level data from patients aged ≥65 years from the phase III LixiLan-O and LixiLan-L studies, which compared iGlarLixi with iGlar and lixisenatide (LixiLan-O only). Efficacy endpoints were changes in glycated hemoglobin A1C, fasting plasma glucose, postprandial glucose, weight, and achievement of A1C <7.

Pegbelfermin (BMS-986036), PEGylated FGF21, in Patients with Obesity and Type 2 Diabetes: Results from a Randomized Phase 2 Study.

Objective: Obesity and type 2 diabetes mellitus (T2DM) are risk factors for nonalcoholic fatty liver disease, including nonalcoholic steatohepatitis. This study assessed pegbelfermin (BMS-986036), recombinant PEGylated human fibroblast growth factor 21 (FGF21), in patients with obesity and T2DM predisposed to fatty liver.

Methods: In this randomized, double-blind, placebo-controlled study, patients with T2DM and BMI of 30 to 50 kg/m received subcutaneous pegbelfermin (1, 5, or 20 mg daily or 20 mg weekly; n = 96) or placebo (n = 24) for 12 weeks.

Impact of lixisenatide dose range on clinical outcomes with fixed-ratio combination iGlarLixi in patients with type 2 diabetes.

Objective: To evaluate the lixisenatide dose range delivered by the iGlarLixi SoloSTAR pen (5-20 µg), alone or in fixed-ratio combination with insulin glargine (iGlar; iGlarLixi).

Methods: Data from three clinical studies were analyzed to assess lixisenatide efficacy and safety: a phase 2a trial assessing gastric emptying effects (ACT6011); a phase 2b dose-ranging trial (DRI6012); and a randomized controlled phase 3 trial comparing iGlarLixi with its components of iGlar and lixisenatide (LixiLan-O). Efficacy metrics included glycated hemoglobin A (A1C), post-prandial glucose (PPG) values following a standardized breakfast, fasting plasma glucose (FPG), and weight change.

Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial.

Background: LY3298176 is a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that is being developed for the treatment of type 2 diabetes. We aimed to examine the efficacy and safety of co-stimulation of the GLP-1 and GIP receptors with LY3298176 compared with placebo or selective stimulation of GLP-1 receptors with dulaglutide in patients with poorly controlled type 2 diabetes.

Methods: In this double-blind, randomised, phase 2 study, patients with type 2 diabetes were randomly assigned (1:1:1:1:1:1) to receive either once-weekly subcutaneous LY3298176 (1 mg, 5 mg, 10 mg, or 15 mg), dulaglutide (1·5 mg), or placebo for 26 weeks.

New Basal Insulins: a Clinical Perspective of Their Use in the Treatment of Type 2 Diabetes and Novel Treatment Options Beyond Basal Insulin.

Purpose Of Review: The purpose of this review was to review advances in basal insulin formulations and new treatment options for patients with type 2 diabetes not achieving glycemic targets despite optimized basal insulin therapy.

Recent Findings: Advances in basal insulin formulations have resulted in products with increasingly favorable pharmacokinetic and pharmacodynamic properties, including flatter, peakless action profiles, less inter- and intra-patient variability, and longer duration of activity. These properties have translated to significantly reduced risk of hypoglycemia (particularly during the night) compared with previous generation basal insulins.

The Sustained Effects of a Dual GIP/GLP-1 Receptor Agonist, NNC0090-2746, in Patients with Type 2 Diabetes.

Unimolecular dual incretins derived from hybridized glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) sequences have demonstrated synergistic reduction of adiposity in animal models and reductions of hyperglycemia in short-duration human trials. Here, we extend the characterization of NNC0090-2746 (also known as RG7697), a fatty-acylated dual agonist possessing in vitro balanced GIPR and GLP-1R agonism. In this 12-week, randomized, placebo-controlled, double-blind phase 2a trial, patients with type 2 diabetes inadequately controlled with metformin received 1.