Tirzepatide

Tirzepatide: Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis.

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease associated with liver-related complications and death. The efficacy and safety of tirzepatide, an agonist of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, in patients with MASH and moderate or severe fibrosis is unclear. We conducted a phase 2, dose-finding, multicenter, double-blind, randomized, placebo-controlled trial involving participants with biopsy-confirmed MASH and stage F2 or F3 (moderate or severe) fibrosis.

Tirzepatide: Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials.

We conducted a systematic review and network meta-analysis to compare the efficacy and safety of s.c. administered tirzepatide vs s.c. administered semaglutide for adults of both sexes with type 2 diabetes mellitus.

Tirzepatide: Efficacy and safety of tirzepatide in children and adolescents with type 2 diabetes (SURPASS-PEDS): a randomised, double-blind, placebo-controlled, phase 3 trial.

Current treatment options for youth-onset type 2 diabetes are limited and have demonstrated lower glycaemic efficacy than those for adult-onset type 2 diabetes. We aimed to assess the safety and efficacy of tirzepatide, a glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist, compared with placebo in youth-onset type 2 diabetes. We conducted a phase 3, double-blind, placebo-controlled, multicentre (39 sites), multinational (eight countries) trial over 30 weeks, followed by an open-label extension for 22 weeks in which all participants received tirzepatide.

Tirzepatide: Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis.

Tirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) currently under review for marketing approval. Individual trials have assessed the clinical profile of tirzepatide vs different comparators. We conducted a systematic review and meta-analysis to assess the efficacy and safety of tirzepatide for type 2 diabetes.

Tirzepatide: Cardiovascular effects of tirzepatide.

Tirzepatide is a first-in-class dual agonist at receptors for glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) for the treatment of T2D and obesity, with unprecedented efficacy for glycaemic control, reductions in body weight and improvements in blood pressure and lipid profile compared with placebo and GLP-1 receptor agonists. To date, clinical trials of tirzepatide have fulfilled the requirement by regulatory authorities of demonstrated cardiovascular safety in high-risk patients. Whether cardiovascular benefits will be found with dual GLP-1/GIP receptor agonists remains uncertain, and the contribution of GIP receptor activation to cardiovascular risk has not been established.

Tirzepatide: Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.

The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown. To assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction. This phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries with a 36-week, open-label tirzepatide lead-in period followed by a 52-week, double-blind, placebo-controlled period included adults with a body mass index greater than or equal to 30 or greater than or equal to 27 and a weight-related complication, excluding diabetes.

Tirzepatide: Safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes and obesity: a systematic review and meta-analysis.

A systematic review and meta-analysis was conducted to synthesize the available data from clinical trials and assess the safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes (T2D) and obesity. A systematic search was conducted in three electronic databases, namely Embase, PubMed, and the Cochrane Library, up until March 1, 2023, to identify randomized controlled trials (RCTs) comparing tirzepatide to either placebo or active hypoglycemic drugs in individuals with T2D and obesity. Heterogeneity was assessed using the I2 value and Cochran's Q test, and a fixed effects model was employed to estimate the safety profile of tirzepatide.

Tirzepatide: Tirzepatide and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis of a randomised, open-label, parallel-group, phase 3 trial.

Substantial weight reduction is often associated with loss of muscle mass. Tirzepatide has been associated with significant reductions in body weight in type 2 diabetes trials and a beneficial effect on body fat distribution in the SURPASS-3 MRI substudy. This post-hoc exploratory analysis studied the association of tirzepatide treatment with changes in thigh muscle volume, muscle volume Z score, and muscle fat infiltration, and aimed to contextualise the results using longitudinal MRI data from UK Biobank participants.

NCT07284511 · RECRUITING

A Clinical Trial Using Tirzepatide to Help Adults With Type 1 Diabetes Automatically Control Their Blood Sugar

This research study is testing whether a weekly medication called tirzepatide can help adults with type 1 diabetes use their insulin pump more easily, specifically by reducing or eliminating the need to count carbohydrates at meals. People with type 1 diabetes must take insulin for life, and even with advanced insulin pumps and continuous glucose monitors, many still struggle to keep blood sugar within the target range. One of the biggest challenges is carbohydrate counting, which requires estimating the amount of carbohydrates in every meal to give the correct insulin dose. Tirzepatide is a medication currently approved for type 2 diabetes and weight management. Early research suggests it may also help people with type 1 diabetes by lowering appetite, slowing digestion, reducing insulin needs, and smoothing after-meal blood sugar rises. This study will include 105 adults with type 1 diabetes at centers in Canada and Switzerland. Everyone will use the Tandem Control-IQ insulin pump with a Dexcom G7 continuous glucose monitor. Participants are randomly assigned to one of two groups: Tirzepatide group: Participants receive weekly tirzepatide injections. After the dose is gradually increased over 12 weeks, they will eventually try using their insulin pump without entering carbohydrate amounts at meals. Control group: Participants continue their usual therapy and keep counting carbohydrates for their mealtime insulin doses. The main goal of the study is to learn whether people taking tirzepatide can safely maintain good blood sugar control without counting carbs, compared with standard care. All participants will attend several clinic visits and share their glucose, insulin, and health data throughout the 32-week trial. Some centers will also conduct heart/fitness, or body-composition tests. As with any medication, tirzepatide may cause side effects such as nausea, vomiting, diarrhea, or decreased appetite. Rare but serious risks like gallbladder disease or pancreatitis are also monitored. Pregnancy must be avoided during the trial. Overall, this study aims to understand whether adding tirzepatide to automated insulin delivery can simplify diabetes management, reduce burden, and maintain safe and effective glucose control for adults living with type 1 diabetes.

NCT05536804 · ACTIVE_NOT_RECRUITING

A Study of Tirzepatide (LY3298176) in Participants With Overweight or Obesity and Chronic Kidney Disease With or Without Type 2 Diabetes

We are doing this study to learn more about how tirzepatide may help fight chronic kidney disease in people with obesity with or without type 2 diabetes (T2D). The study will last about 56 weeks and include up to 12 visits.

NCT07567378 · NOT_YET_RECRUITING

CARTIZ Registry: Cartilage, Arthropathy and Imaging Under Tirzepatide in Zone-stratified Cohorts - A Four-Institute Mexican Observational Registry

CARTIZ is a prospective observational clinical registry of adults in Mexico receiving tirzepatide (a dual GLP-1/GIP receptor agonist) under an independent clinical indication - typically type 2 diabetes, insulin resistance, obesity, renal protection, metabolic hypertension, or associated off-label metabolic use. The registry is entirely observational: CARTIZ does not initiate, modify, interrupt, or supply tirzepatide, and does not dictate dose, route, or duration. All pharmacological exposure decisions are made by the treating physician independently of study participation. The registry is operationalized through a four-institute architecture integrating three Mexican National Institutes of Health and one national imaging laboratory. Core 1 (Knee Cartilage Imaging, Ci3M UAM-Iztapalapa) performs bilateral 3T MRI with quantitative T2 mapping at Week 0 and Week 52. Core 2 (Cardiac Imaging, Instituto Nacional de Cardiología Ignacio Chávez) performs non-contrast cardiac computed tomography for radiomic phenotyping of epicardial adipose tissue at Week 0 and Week 52 under cardiovascular Co-Principal Investigator Dr. Erick Alexánderson Rosas. Core 3 (HLA Typing, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Transplant Department) performs Class I and Class II HLA typing by PCR-SSO Reverse Luminex. Core 4 (Body Composition, Universidad La Salle México) performs multi-frequency bioelectrical impedance analysis (seca mBCA) at six longitudinal timepoints capturing visceral adipose tissue trajectory, phase-angle trajectory, appendicular skeletal muscle mass, and hydration ratios at zero marginal cost. The registry enrolls n=30 patients across three clinical sites with identical protocol (IMSS Clínica Río Magdalena, INCMNSZ outpatient clinic, and a private practice site in Mexico City), generating 60 evaluable knees and 30 paired cardiac CT studies. The primary co-endpoints address a mechanistic question no other tirzepatide study is positioned to answer: whether the articular response to tirzepatide in inflammatory arthropathy precedes and mechanistically precedes weight loss, through formal mediation analysis of Week-4 ACR20 response via high-sensitivity C-reactive protein, SERPINB2, and dipeptidyl peptidase-4 activity, restricted to the Mechanistic Analysis Set of patients with tirzepatide exposure ≤16 weeks at Week 0 and delta-BMI \<1.0 kg/m² through Week 4. A prespecified Surgical Tissue Subcohort is declared at initial registration to establish public scientific priority on direct human epicardial adipose tissue transcriptomic characterization under dual GIP/GLP-1 receptor agonism. Subcohort participants who undergo clinically indicated cardiac surgery at INCar during follow-up (coronary artery bypass grafting, valve replacement, or combined procedures) are invited to provide specific additional informed consent for collection of epicardial adipose tissue fragments routinely excised during operative access and otherwise discarded as surgical waste. Operational launch is contingent on separate INCar tissue-specific approvals and will proceed via PRS record amendment when ready

NCT05822544 · ACTIVE_NOT_RECRUITING

Phase 1/1b Study of TLC-6740 in Healthy Subjects and Subjects With Obesity, With or Without Diabetes

The phase 1 portion of the study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TLC-6740 after single- and multiple-ascending doses in healthy subjects. The phase 1b portion of the study is designed to assess the safety, tolerability, and PK of TLC-6740 in subjects with obesity, with or without type 2 diabetes mellitus.

NCT03882970 · COMPLETED

A Study of Tirzepatide (LY3298176) Versus Insulin Degludec in Participants With Type 2 Diabetes

The purpose of this study is to compare the effect of the study drug tirzepatide to insulin degludec on blood sugar levels in participants with type 2 diabetes. The study will last about 67 weeks and may include up to 22 visits.

NCT02759107 · COMPLETED

A Study of Tirzepatide (LY3298176) in Healthy Participants and Participants With Type 2 Diabetes (T2DM)

The main purposes of this study are to determine: * The safety of tirzepatide and any side effects that might be associated with it. * How much tirzepatide gets into the bloodstream and how long it takes the body to get rid of it. * How tirzepatide affects the levels of blood sugar. This study includes 3 parts (A, B and C). Part A involves a single dose of tirzepatide taken as a subcutaneous (SC) injection just under the skin and will be approximately 10 weeks in duration, including screening. Parts B and C involve 4 doses of tirzepatide taken once weekly (over 4 weeks) as a SC injection just under the skin and is approximately 12-14 weeks in duration, including screening. Each participant will enroll in only one part. This study is for research purposes only, and is not intended to treat any medical condition.