Rutherford slide

Nov 6, 20121 like355 views

This study assessed the effectiveness and safety of AMG145, a human monoclonal antibody to PCSK9, in patients with heterozygous familial hypercholesterolemia (HeFH) who were on intensive statin therapy but unable to reach LDL-C treatment goals. At 12 weeks, patients receiving 350 mg or 420 mg of AMG145 subcutaneously every 4 weeks saw LDL-C level reductions of 43% and 55% respectively, compared to a 1% increase in the placebo group. No serious adverse events occurred. AMG145 may provide an effective additional treatment to help more HeFH patients reach their LDL-C goals.

Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial
Hypercholesterolemia Disorder (RUTHERFORD): Interim Results from a
Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial
• Background: Heterozygous familial • Results: At week 12, percent change in LDL-C levels
hypercholesterolemia (HeFH) is a common genetic were -43% in the 350 mg AMG145 group, -55% in the
disorder that causes many patients not to reach LDL-C 420 mg AMG145 group and an increase of 1% in the
treatment goals, even with statin therapy. Plasma placebo group. No serious treatment-related adverse
proprotein convertase subtilisin/kexin type 9 (PCSK9) events occurred.
binds LDL receptors, therefore increasing levels of LDL-
• Conclusion: AMG145 may provide effective additional
C in the blood. Phase 1 studies of a human monoclonal
LDL-C lowering treatment in HeFH patients on intensive
antibody to PCSK9, AMG145, have shown tolerance
statin therapy.
and effectiveness in lowering LDL-C.
• Purpose: To assess the effectiveness and safety of Percent of Patients Treated to LDL-C Goal at Week 12
AMG145 in patients with HeFH.
Treatment LDL-C < 100 LDL-C < 70
• Methods: In this 12-week, randomized, double-blind, mg/dL mg/dL
placebo-controlled study, 167 patients were
350 mg AMG145 70% 44%
randomized to one of 3 treatments: 350 mg of
AMG145, 420 mg of AMG145 or placebo administered
420 mg AMG145 89% 65%
subcutaneously every 4 weeks. Primary endpoint was
percent change in LDL-C levels from baseline to 12
Placebo 2% 0%
weeks.

Presented by: Raal F, AHA Scientific Sessions, Los Angeles © 2012, American Heart Association. All rights reserved.

The document summarizes current immunotherapies being developed for the treatment of type 1 diabetes. It describes how autoimmunity leads to the destruction of beta cells and the goals of immunotherapy to slow or stop this process. Several antigen-specific therapies targeting proteins like GAD, insulin, and HSP60 as well as monoclonal antibodies, fusion proteins, and Treg affectors are discussed. Clinical trials for many of these candidates showed only transient effects in preserving beta cell function and glycemic control with no therapy providing a lasting halt to the autoimmune attack. Combination therapies and identifying the best patient populations may improve outcomes but ideal timing and dosing remain unclear.

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New Treatments for Severe HypercholesteremiaAllina Health

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PCSK9 Inhibitors PPVince Netto

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This document discusses PCSK9 inhibitors, which are a new class of drugs for treating hyperlipidemia. It describes three PCSK9 inhibitors in development (alirocumab, evolocumab, bococizumab) and summarizes results from clinical trials of alirocumab and evolocumab. When added to statin therapy, these PCSK9 inhibitors provided additional LDL cholesterol reductions of 30-60% compared to placebo or ezetimibe alone in many trials. Larger outcomes trials are still ongoing to determine if PCSK9 inhibitors can also reduce cardiovascular events when added to statins. Current lipid guidelines prefer high-intensity statins but allow adding non-statin drugs like

Linagliptin Endocrinologist Prespective - Case.pptxAmeetRathod3

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A 63-year-old man with type 2 diabetes and chronic kidney disease visited his doctor with complaints of increased fatigue and two episodes of hypoglycemia. He has a history of diabetes for 11 years and hypertension for 6.5 years. Laboratory tests showed uncontrolled diabetes with an HbA1c of 9.0% and declining renal function, with an eGFR of 51 mL/min/1.73m2 and a urinary albumin-to-creatinine ratio of 435 mg/g, indicating high risk of cardiovascular disease and progression of kidney disease. The patient is currently taking metformin, glimepiride, sitagliptin, and antihypertensive medications.

Evolocumab in hyperlipidemianiteshpansari

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1) The document describes a 52-week placebo-controlled trial that compared evolocumab (a monoclonal antibody that inhibits PCSK9) to placebo in patients with hyperlipidemia receiving background lipid-lowering therapy. 2) The primary endpoint was the percent change from baseline in LDL-C levels at week 52. Evolocumab produced a 57% reduction in LDL-C on average compared to placebo. 3) Evolocumab also significantly reduced levels of other atherogenic lipids like apolipoprotein B and lipoprotein(a) while modestly increasing HDL cholesterol. More than 80% of patients receiving evolocumab achieved a target LDL-C level of under 70 mg/dL.

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Dr. Vivek Baliga discusses diabetic dyslipidemia and emerging concepts in its management. Non-HDL cholesterol is a better indicator of cardiovascular risk than LDL cholesterol. It encompasses all potentially atherogenic lipoproteins. Dual PPAR alpha/gamma agonists like saroglitazar can effectively control dyslipidemia and maintain glycemic control in patients with diabetes by reducing triglycerides and non-HDL cholesterol while improving other lipid and glucose parameters. Saroglitazar is approved in India for the treatment of diabetic dyslipidemia.

Target ldl levels in extreme high risk acs. acheiving the goalDr MD TALHA KHAN ABID

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- The document discusses guidelines for lowering LDL cholesterol levels in patients at extreme high risk of cardiovascular events based on recent studies. - Studies such as IMPROVE-IT, ODYSSEY OUTCOMES, and FOURIER showed that adding ezetimibe, alirocumab (PCSK9 inhibitor), or evolocumab (PCSK9 inhibitor) to statin therapy provided additional reduction in LDL cholesterol and reduced cardiovascular events compared to statin therapy alone in high-risk patients. - Other studies found medications like inclisiran, bempedoic acid, and the combination of bempedoic acid and ezetimibe also significantly lowered LDL cholesterol

Design and Synthesis of some Pyrimidine as DPP-IV Inhibitorsmohd imran Ahmad

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This document presents the work plan for designing and synthesizing novel pyrimidine derivatives as DPP-IV inhibitors for the treatment of type 2 diabetes. The plan involves performing in silico molecular docking studies to design compounds with good binding affinity for DPP-IV. Five series of compounds will be synthesized and characterized. The aim is to develop potent and selective DPP-IV inhibitors with improved pharmacological properties compared to existing drugs like sitagliptin. Molecular docking studies identified compounds from each series with binding scores comparable or better than sitagliptin, indicating promise as antidiabetic agents. The synthesized compounds will help advance the treatment of type 2 diabetes.

UPDATE ON THE PCKS9 INHIBITION TO LOWER LDL CHOLESTEROLPraveen Nagula

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1) Evolocumab, a PCSK9 inhibitor monoclonal antibody, significantly lowered LDL cholesterol in multiple clinical trials across different patient populations and background lipid-lowering therapies. 2) While evolocumab demonstrated generally favorable safety and significant LDL reductions, its ability to improve cardiovascular outcomes requires confirmation from long-term outcomes trials like FOURIER. 3) First generation sirolimus-eluting stents demonstrated better outcomes than a second generation zotarolimus-eluting stent at 1 year follow up, but this advantage was lost by 5 years due to higher rates of late stent thrombosis and target vessel revascularization with the first generation stent.

Alogliptin A Review of its Use in Management of Type 2 Diabetes Mellitus.pptxKashish Goyal

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DIABETES Y ENFERMEDAD CARDIOVASCULAR 23NOVIEMBRE18 CRISTOBAL MORALES PORTILLO

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PCSK9 InhibitorsTerri Newman

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Novel approaches in Lipid ManagementShashikiran Umakanth

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Statins are highly effective LDL-c lowering agents that actually reduce clinical cardiovascular events. The 2013 ACC/AHA guidelines on the management of blood cholesterol recommend high-intensity statin therapy in individuals with high cardiovascular risk as assessed by the 10-year atherosclerotic cardiovascular disease risk calculator. However, a significant number of individuals do not tolerate or respond adequately to statins, and continue to have residual risk in spite of high intensity statin therapy. There are some exciting developments in the field of lipidology. This decade has been labeled “The PCSK9 decade”. A new class of monoclonal antibodies directed against the PCSK9 glycoproteins appears very promising in further lowering LDL cholesterol and thereby cardiovascular risk. Evolocumab and alirucomab are novel PCSK9 inhibitors that can be given subcutaneously once or twice in a month, and have the potential to reduce LDL-cholesterol to very low levels without any major adverse effects. Other classes of drugs like Apo-B antisense oligonucleotides (mipomersen), CETP inhibitors (especially anacetrapib), microsomal transfer protein inhibitors (lomitapide) also hold some promise. The future of lipid lowering therapy looks reassuring with these new developments. Shashikiran Umakanth presented this at the Egyptian Association of Endocrinology, Diabetes & Atherosclerosis (EAEDA) 2014 conference at Alexandria, Egypt. This conference was help in association with Endocrine Society, USA and the European Association for the Study of Diabetes (EASD).

Confidence_Alogliptin_13_Mar_2023 (1).pptxsaleemaitm

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Dr. Tinahones - Simposio lanzamiento alirocumabCampus Sanofi

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The document discusses PCSK9 inhibitors and their potential role in treating patients with diabetes. It summarizes several key studies on alirocumab, a PCSK9 inhibitor, in patients with diabetes. Results showed that alirocumab significantly reduced LDL-C levels in patients with diabetes, with an efficacy and safety profile similar to patients without diabetes. Further studies are exploring the effects of alirocumab on glycemic control and progression from prediabetes to diabetes. The document concludes that alirocumab may have an important role in treating hypercholesterolemia in patients with diabetes according to new guidelines.

New microsoft power point presentationDr Bikash Chandra Paul

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Mrs. Asma Khatun, a 45-year-old woman, was admitted to the hospital with generalized weakness, fever, and cough. Tests revealed she had severe anemia with a hemoglobin level of 5.6 gm/dl, and inflammatory lesions in her lungs. She received multiple blood transfusions. Further tests showed she has multiple myeloma, with over 80% plasma cells in her bone marrow. She was diagnosed with multiple myeloma and autoimmune hemolytic anemia. Treatment for multiple myeloma may include combinations of drugs like lenalidomide, bortezomib, and dexamethasone. Prognosis depends on factors like age, kidney function, and myeloma stage.

Recent advances in dyslipidemiaSeth GSMC and KEM Municipal Hospital

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Linagliptin Endocrinologist Prespective - Case.pptxAmeetRathod3

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Linagliptin in DKD.pptxAmeetRathod3

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Linagliptin is a DPP-4 inhibitor that provides long-lasting inhibition of DPP-4 and modestly increases GLP-1 levels. Studies have shown linagliptin to have neutral effects on glomerular filtration rate and renal plasma flow compared to glimepiride in patients with type 2 diabetes without renal impairment. Additionally, linagliptin tended to reduce urinary albumin-to-creatinine ratio compared to glimepiride with no significant between-group differences. These renal effects are consistent with previous placebo-controlled trials, demonstrating linagliptin's neutral impact on renal hemodynamics.

Sglt 2 inhibiors in cardiovascular diseasesYogesh Shilimkar

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This document summarizes the history and mechanisms of action of SGLT2 inhibitors, a class of diabetes medications. Key points include: - SGLT2 inhibitors work by blocking glucose reabsorption in the kidney, inducing glucosuria and lowering blood glucose levels. - Several large clinical trials demonstrated SGLT2 inhibitors effectively lower HbA1c and blood glucose with a low risk of hypoglycemia compared to other diabetes medications. - Beyond glycemic control, SGLT2 inhibitors provide additional benefits like weight loss, blood pressure reduction, and improved cardiac outcomes.

Saroglitazar in nash Journal Dr Priya.pptxSyedFurqan30

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Acute complications of diabetes mellitusGofasefer

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Ezzahti sijbrands mulder roeters van lennep familial hypercholesterolemia new...Marilyn Mann

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This document summarizes new treatment options for familial hypercholesterolemia (FH), a genetic disorder associated with high cholesterol and increased risk of heart disease. It describes recent clinical trial results of monoclonal antibodies against PCSK9 (REGN727 and AMG145) that lowered LDL cholesterol by up to 68% with minimal side effects. It also discusses mipomersen, an inhibitor of apolipoprotein B synthesis that lowered LDL by 21-47% but was associated with elevated liver enzymes in 6-15% of patients, raising safety concerns. The new drugs show promise for improving cholesterol levels in FH patients but require further study of their long-term safety and impact on heart disease outcomes.

Two phase 3 trials of inclisiran in patients-1.pptxseethu300996

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Clinical trail drugAlFahadUlIslam1

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Ueda2015 lilly.the art of insulin dr.mesbah sayedueda2015

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This document discusses the treatment of a 52-year-old patient with type 2 diabetes who has an HbA1c of 9.4% despite treatment with oral medications. It considers adding insulin therapy to help control the patient's blood glucose levels and reach treatment targets. Specifically, it compares the effectiveness of premixed insulin versus basal insulin when initiating insulin in type 2 diabetes patients. A study is summarized that found premixed insulin administered twice daily in combination with metformin was more effective at reducing HbA1c and post-prandial blood glucose compared to a basal insulin administered once daily plus metformin. The document advocates for patient-centered treatment approaches and discusses factors to consider when choosing between premixed versus basal-bolus insulin reg

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Rutherford slide

1. Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD): Interim Results from a Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial • Background: Heterozygous familial • Results: At week 12, percent change in LDL-C levels hypercholesterolemia (HeFH) is a common genetic were -43% in the 350 mg AMG145 group, -55% in the disorder that causes many patients not to reach LDL-C 420 mg AMG145 group and an increase of 1% in the treatment goals, even with statin therapy. Plasma placebo group. No serious treatment-related adverse proprotein convertase subtilisin/kexin type 9 (PCSK9) events occurred. binds LDL receptors, therefore increasing levels of LDL- • Conclusion: AMG145 may provide effective additional C in the blood. Phase 1 studies of a human monoclonal LDL-C lowering treatment in HeFH patients on intensive antibody to PCSK9, AMG145, have shown tolerance statin therapy. and effectiveness in lowering LDL-C. • Purpose: To assess the effectiveness and safety of Percent of Patients Treated to LDL-C Goal at Week 12 AMG145 in patients with HeFH. Treatment LDL-C < 100 LDL-C < 70 • Methods: In this 12-week, randomized, double-blind, mg/dL mg/dL placebo-controlled study, 167 patients were 350 mg AMG145 70% 44% randomized to one of 3 treatments: 350 mg of AMG145, 420 mg of AMG145 or placebo administered 420 mg AMG145 89% 65% subcutaneously every 4 weeks. Primary endpoint was percent change in LDL-C levels from baseline to 12 Placebo 2% 0% weeks. Presented by: Raal F, AHA Scientific Sessions, Los Angeles © 2012, American Heart Association. All rights reserved.

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Rutherford slide

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