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2.
Drugs ; 84(2): 227-238, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38388874

RESUMO

Tirzepatide (Mounjaro®), a first-in-class dual incretin agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, is approved for use as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus (T2DM) in the USA, EU, Japan and other countries. It comes as single-dose prefilled pens and single-dose vials. In phase III SURPASS trials, once-weekly subcutaneous tirzepatide, as monotherapy or add-on-therapy to oral glucose-lowering medications and insulin, was superior to the GLP-1 receptor agonists (RAs) dulaglutide 0.75 mg and semaglutide 1 mg as well as basal and prandial insulin for glycaemic control and weight loss in adults with inadequately controlled T2DM. Tirzepatide was generally well tolerated, with a safety profile consistent with that of GLP-1 RAs. Tirzepatide was associated with a low risk of clinically significant or severe hypoglycaemia and no increased risk of major adverse cardiovascular events. Adverse events were mostly mild to moderate in severity, with the most common being gastrointestinal events including nausea, diarrhoea, decreased appetite and vomiting. In conclusion, tirzepatide is a valuable addition to the treatment options for T2DM.


Many people with type 2 diabetes mellitus (T2DM) do not achieve and maintain glycaemic and weight management goals using currently available treatments. Tirzepatide (Mounjaro®) is the first incretin-based glucose-lowering medication to be approved as an add-on to diet and exercise in adults with T2DM that targets both the glucose-dependent insulinotropic polypeptide receptor (GIP) and the glucagon-like peptide-1 (GLP-1) receptor. In patients with inadequately controlled T2DM, tirzepatide improved glycaemic control and body weight more so than dulaglutide 0.75 mg, semaglutide 1 mg and insulin when used on its own or in combination with other medications. Tirzepatide was generally well tolerated and had a low risk of hypoglycaemia. The most common adverse events were usually short-lived gastrointestinal-related events, which were generally mild to moderate in nature, including nausea, diarrhoea, decreased appetite and vomiting. Tirzepatide is a valuable addition to the treatment options for people with inadequately controlled T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Polipeptídeo Inibidor Gástrico , Receptor do Peptídeo Semelhante ao Glucagon 2 , Adulto , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina , Receptor do Peptídeo Semelhante ao Glucagon 1 , Glucose , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico
3.
Target Oncol ; 19(1): 115-123, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38236364

RESUMO

Tremelimumab (tremelimumab-actl; Imjudo®) is a monoclonal antibody and immune checkpoint inhibitor (ICI) that blocks cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). A single, priming dose of intravenous tremelimumab is used in combination with durvalumab, an ICI that blocks programmed cell-death ligand 1, in a regimen known as STRIDE (Single Tremelimumab Regular Interval Durvalumab). STRIDE is approved for the treatment of adults with unresectable hepatocellular carcinoma (HCC) in the USA and Japan and for the first-line treatment of adults with advanced or unresectable HCC in Europe. In the phase III HIMALAYA trial, STRIDE significantly improved overall survival (OS) compared with sorafenib in adults with unresectable HCC and no prior systemic therapy. A higher proportion of STRIDE versus sorafenib recipients had an objective response to treatment. The OS benefit associated with STRIDE was sustained with 4 years' follow-up. STRIDE had a manageable safety profile that differed from that of sorafenib. Grade 3 or 4 treatment-related adverse events occurred in a lower proportion of STRIDE versus sorafenib recipients. Based on the available evidence, tremelimumab used as part of the STRIDE regimen is a valuable first-line agent that expands the treatment options available to patients with advanced or unresectable HCC.


Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a leading cause of cancer death worldwide. HCC is commonly associated with cirrhosis linked to chronic viral hepatitis and non-alcoholic fatty liver disease. Tremelimumab (tremelimumab-actl; Imjudo®) is a type of immunotherapy that helps the body's immune system attack HCC cells by binding to and blocking the action of an immune-checkpoint protein called cytotoxic T lymphocyte-associated antigen-4. A single dose of intravenous tremelimumab is used in combination with treatment with durvalumab, in a regimen known as STRIDE (Single Tremelimumab Regular Interval Durvalumab), for adults with unresectable HCC in the USA and Japan and as a first-line treatment for adults with advanced or unresectable HCC in the EU. In patients with unresectable HCC, STRIDE improved overall survival more than sorafenib, including at 4 years' follow-up. A higher proportion of patients responded to treatment with STRIDE compared with sorafenib. STRIDE had manageable adverse events. Tremelimumab used as part of the STRIDE regimen is a valuable first-line agent that expands the treatment options available to patients with HCC that is advanced or unable to be removed with surgery.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico
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