Immunogenicity, efficacy, and safety of biosimilar insulin glargine (Gan & Lee glargine) compared with originator insulin glargine (Lantus®) in patients with type 2 diabetes after 26 weeks' treatment: A randomized open label study.

Aim: To evaluate the equivalence of immunogenicity, safety and efficacy of Gan & Lee (GL) Glargine (Basalin®; Gan & Lee Pharmaceutical) with that of the reference product (Lantus®) in adult participants with type 2 diabetes mellitus.

Methods: This was a phase 3, multicenter, open-label, equivalence trial conducted across 57 sites. In total, 567 participants with type 2 diabetes mellitus were randomized in a 1:1 ratio to undergo treatment with either GL Glargine or Lantus® for 26 weeks.

Effectiveness of a Novel ω-3 Krill Oil Agent in Patients With Severe Hypertriglyceridemia: A Randomized Clinical Trial.

Importance: Intense interest exists in novel ω-3 formulations with high bioavailability to reduce blood triglyceride (TG) levels.

Objective: To determine the phase 3 efficacy and safety of a naturally derived krill oil with eicosapentaenoic acid and docosahexaenoic acid as both phospholipid esters (PLs) and free fatty acids (FFAs) (ω-3-PL/FFA [CaPre]), measured by fasting TG levels and other lipid parameters in severe hypertriglyceridemia.

Design, Setting, And Participants: This study pooled the results of 2 identical randomized, double-blind, placebo-controlled trials.

Icosabutate for the treatment of very high triglycerides: A placebo-controlled, randomized, double-blind, 12-week clinical trial.

Background: Icosabutate is a structurally enhanced omega-3 fatty acid molecule developed with the aim of achieving improved triglyceride (TG)-lowering efficacy, increased potency, and preserved safety compared with conventional prescription omega-3 fatty acid.

Objective: To evaluate the efficacy and safety of icosabutate 600 mg once daily in patients with very high TGs.

Methods: After a 6-8 week run-in period, men and women with TG levels ≥ 500 mg/dL and ≤ 1500 mg/dL were randomized to double-blind treatment with placebo or icosabutate 600 mg for 12 weeks.

JCL Roundtable: Gender differences in risk reduction with lifestyle changes.

The first efforts to uncover the causes of cardiovascular disease focused on the behavioral, now called lifestyle habits of populations. Diet, exercise, and smoking were recognized as important issues with strong relationships in community-based observational studies such as the Seven Countries study, the Framingham Heart Study, and the Western Electric Study in Chicago. The first meaningful intervention in the United States was the dietary recommendations made by the American Heart Association in 1963 and the Surgeon General's Report on Smoking and Health in 1964.

Effects of Xuezhikang in patients with dyslipidemia: a multicenter, randomized, placebo-controlled study.

Background: Xuezhikang (XZK) is an extract of fermented red yeast rice that has lipid-lowering properties.

Objective: To evaluate the effects of XZK on lipids in subjects with dyslipidemia but no coronary heart disease.

Methods: A total of 116 adults with baseline non-high-density lipoprotein cholesterol (non-HDL-C) levels of approximately 208 mg/dL and low-density lipoprotein cholesterol (LDL-C) levels of approximately 175 mg/dL were randomized to either placebo or XZK 1200 or 2400 mg daily and treated for 12 weeks.

Colesevelam, Ezetimibe, and Patients With Type 2 Diabetes Mellitus: Characteristics and Clinical Outcomes From a Health Care Database.

Background: Despite the prevalence of therapies available to patients at highest coronary heart disease risk, only a minority of type 2 diabetes mellitus (T2DM) patients reach desired cholesterol treatment levels, with limited data regarding their outcomes.

Objective: To examine "real-world" effectiveness of initiating treatment with either colesevelam or ezetimibe among individuals with evidence of T2DM and hypercholesterolemia (HCh). Key outcomes included treatment patterns and cardiovascular (CV) events.

Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab.

Objectives: The aim of this study was to compare biweekly and monthly evolocumab with placebo and oral ezetimibe in patients with hypercholesterolemia in a phase III trial.

Background: Evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced LDL-C in phase II trials.

Methods: Patients 18 to 80 years of age with fasting low-density lipoprotein cholesterol (LDL-C) ≥100 and <190 mg/dl and Framingham risk scores ≤10% were randomized (1:1:1:1:2:2) to oral placebo and subcutaneous (SC) placebo biweekly; oral placebo and SC placebo monthly; ezetimibe and SC placebo biweekly; ezetimibe and SC placebo monthly; oral placebo and evolocumab 140 mg biweekly; or oral placebo and evolocumab 420 mg monthly.

Consistency of extended-release niacin/laropiprant effects on Lp(a), ApoB, non-HDL-C, Apo A1, and ApoB/ApoA1 ratio across patient subgroups.

Background: According to prior analyses, extended-release niacin/laropiprant (ERN/LRPT) consistently reduces low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) and increases high-density lipoprotein cholesterol (HDL-C) levels across a wide range of dyslipidemic patient subgroups.

Objectives: This analysis examined ERN/LRPT's consistency across four phase III, randomized, double-blind trials in improving other lipid/lipoprotein parameters associated with cardiovascular risk, across several key dyslipidemic patient subgroups.

Methods: In three of the studies, the randomized population included patients with primary hypercholesterolemia or mixed hyperlipidemia; in the remaining study, the population included patients with type 2 diabetes mellitus.

Phentermine/topiramate for weight reduction and treatment of adverse metabolic consequences in obesity.

Phentermine hydrochloride is a noradrenergic sympathetic amine approved for decades by the U.S. Food and Drug Administration (FDA) at doses as high as 37.

MBX-8025, a novel peroxisome proliferator receptor-delta agonist: lipid and other metabolic effects in dyslipidemic overweight patients treated with and without atorvastatin.

Context: Preclinical and clinical studies suggest that peroxisome proliferator-activated receptor (PPAR)-δ agonists favorably affect multiple metabolic parameters that are otherwise proatherogenic, many that are not optimally managed with statins alone.

Objective: The aim of this study was to evaluate the effects of MBX-8025 (a novel PPAR-δ agonist) on lipid and other metabolic parameters associated with increased atherosclerotic risk, administered alone and in combination with atorvastatin.

Design And Setting: This was a randomized, double-blind, placebo-controlled, parallel group proof-of-concept study conducted at 30 U.

Extended-release niacin/laropiprant lipid-altering consistency across patient subgroups.

Background: In patients with primary hypercholesterolemia or mixed dyslipidemia, extended-release niacin/laropiprant (ERN/LRPT) improves key lipid parameters associated with increased atherosclerotic coronary heart disease (CHD) risk.

Aim: This analysis examined data from four Phase III, randomised, double-blind trials to determine the consistency of ERN/LRPT's lipid-altering efficacy among subgroups of patients.

Methods: Data from four Phase III, randomised, double-blind trials of ERN/LRPT were analysed to determine the consistency of ERN/LRPT's lipid-altering efficacy among subgroups of gender, race (white, non-white), region (US, ex-US), baseline age (<65, ≥65 years), use of statin therapy, CHD risk status (low, multiple, high) and type of hyperlipidemia (primary hypercholesterolemia, mixed dyslipidemia), as well as across baseline low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels.

Effects of coadministered ezetimibe plus fenofibrate in mixed dyslipidemic patients with metabolic syndrome.

Objective: Patients with metabolic syndrome are at increased risk of atherosclerotic coronary heart disease, often have mixed dyslipidemia, and may thus require more aggressive treatment of multiple lipid parameters. The objective of this investigation was to compare the treatment response of ezetimibe co-administered with fenofibrate in mixed dyslipidemic patients with and without metabolic syndrome.

Methods: This post hoc analysis evaluated 625 patients 18-75 years of age with mixed dyslipidemia, defined as elevated low-density lipoprotein cholesterol (LDL-C) levels (130-220 mg/dL) and elevated triglycerides (TG) levels (200-500 mg/dL).

Phentermine, topiramate and their combination for the treatment of adiposopathy ('sick fat') and metabolic disease.

Positive caloric balance often causes pathologic adipocyte and adipose tissue anatomical and functional changes (termed adiposopathy or 'sick fat'), which may lead to pathogenic adipocyte and adipose tissue responses and metabolic disease. Fat weight loss may improve adiposopathy, and thus improve metabolic disease in overweight patients. Unfortunately, the efficacy of non-surgical weight loss therapies is often limited due to redundant physiological systems that help 'protect' against starvation and/or negative caloric balance.

What's the deal with niacin development: is laropiprant add-on therapy a winning strategy to beat a straight flush?

Purpose Of Review: Niacin is a B-complex vitamin used as a lipid-altering drug since the 1950s. Niacin improves multiple lipid parameters. Atherosclerotic coronary heart disease outcome studies support niacin's efficacy in reducing coronary heart disease events, either as monotherapy or when used in combination with other lipid-altering drugs.

Is adiposopathy (sick fat) an endocrine disease?

Objective: To review current consensus and controversy regarding whether obesity is a 'disease', examine the pathogenic potential of adipose tissue to promote metabolic disease and explore the merits of 'adiposopathy' and 'sick fat' as scientifically and clinically useful terms in defining when excessive body fat may represent a 'disease'.

Methods: A group of clinicians and researchers, all with a background in endocrinology, assembled to evaluate the medical literature, as it pertains to the pathologic and pathogenic potential of adipose tissue, with an emphasis on metabolic diseases that are often promoted by excessive body weight.

Results: The data support pathogenic adipose tissue as a disease.

Safety of niacin and simvastatin combination therapy.

Niacin is the most potent lipid-altering agent for raising high-density lipoprotein (HDL) cholesterol levels. Niacin also lowers triglyceride (TG) levels, lowers low-density lipoprotein (LDL) cholesterol levels, and improves lipoprotein particle size and subclass distribution. Niacin's major adverse experience (AE) is flushing.

Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity.

When caloric intake exceeds caloric expenditure, the positive caloric balance and storage of energy in adipose tissue often causes adipocyte hypertrophy and visceral adipose tissue accumulation. These pathogenic anatomic abnormalities may incite metabolic and immune responses that promote Type 2 diabetes mellitus, hypertension and dyslipidemia. These are the most common metabolic diseases managed by clinicians and are all major cardiovascular disease risk factors.

Colesevelam hydrochloride: reducing atherosclerotic coronary heart disease risk factors.

Colesevelam HCl is a bile acid sequestrant (BAS) which has been specifically designed with a unique structure for the purpose of improving tolerability and reducing potential drug interactions compared to older BAS, such as cholestyramine and colestipol. As a class, BAS are known to reduce cholesterol and glucose levels, and to reduce atherosclerotic coronary heart disease (CHD) risk as monotherapy, and in combination with other lipid-altering drug therapies. Colesevelam HCl has specifically been shown to reduce total and low-density lipoprotein (LDL) cholesterol levels, and has been approved as a cholesterol-lowering drug since year 2000.

Adiposopathy: treating pathogenic adipose tissue to reduce cardiovascular disease risk.

Excessive adipose tissue is potentially pathogenic due to its mass effects and through adverse metabolic/immune responses, which may lead to cardiovascular disease risk factors (eg, type 2 diabetes mellitus, hypertension, dyslipidemia, and possibly atherosclerosis itself). Positive caloric balance in genetically/environmentally susceptible patients may result in adipocyte hypertrophy, visceral adipose tissue accumulation, and ectopic fat deposition, all causally associated with metabolic disease, and all anatomic manifestations of "adiposopathy" (a term used to describe adipose tissue pathology). Weight loss through improved nutrition, increased physical activity, and weight loss agents (ie, orlistat and sibutramine) improves adiposopathy and improves many metabolic diseases whose prevalence are directly associated with an increase in body fat and sedentary lifestyle.

Adiposopathy: how do diet, exercise and weight loss drug therapies improve metabolic disease in overweight patients?

An increase in bodyweight is generally associated with an increased risk of excessive fat-related metabolic diseases (EFRMD), including Type 2 diabetes mellitus, hypertension and dyslipidemia. However, not all patients who are overweight have EFRMD, and not all patients with EFRMD are significantly overweight. The adipocentric paradigm provides the basis for a unifying, pathophysiological process whereby fat gain in susceptible patients leads to fat dysfunction ('sick fat'), and wherein pathological abnormalities in fat function (adiposopathy) are more directly related to the onset of EFRMD than increases in fat mass (adiposity) alone.

The melanocortin system as a therapeutic treatment target for adiposity and adiposopathy.

The melanocortin system is an important treatment target towards improving both adiposity (excessive body fat) and adiposopathy (dysfunctional body fat). Melanocortin agonism can be achieved by increasing CNS leptin and/or insulin activity, which is dependent upon peripheral leptin/insulin production, transport across the blood-brain barrier (potentially relevant to inhaled/nasal insulin), and effects upon CNS target receptors. Melanocortin agonism may also be achieved through inhibiting inverse agonists of melanocortin receptors (such as inhibition of agouti-related peptide), and directly through selective melanocortin receptor ligands such as piperazine, piperidine, pyridazinone, tetrahydropyran, thiadiazole and diazole derivatives.

Clinical overview of Omacor: a concentrated formulation of omega-3 polyunsaturated fatty acids.

Omacor (omega-3-acid ethyl esters; Reliant Pharmaceuticals, Inc., Liberty Corner, NJ) is a highly purified, prescription omega-3 fatty acid formulation with high concentrations of eicosapentaenoic acid (EPA) (465 mg) and docosahexaenoic acid (DHA) (375 mg) in each 1-g capsule, along with 4 mg (6 IU) of vitamin E. At a typical dose of 4 capsules/day, Omacor significantly lowers plasma triglyceride levels either as monotherapy or in combination with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) or fibrates.

Adiposopathy is a more rational treatment target for metabolic disease than obesity alone.

Current guidelines recommend that weight-loss therapy should be primarily based upon specific body mass index (BMI) cut-off limits. However, in the adipocentric paradigm, it is acknowledged that co-morbidities, such as type 2 diabetes mellitus, hypertension, and dyslipidemia, occur at all levels of BMI. Excessive fat mass (adiposity) in genetically susceptible individuals results in fat dysfunction (adiposopathy), which then contributes to metabolic disorders that increase the risk of atherosclerotic cardiovascular disease.

Torcetrapib/atorvastatin combination therapy.

Elevated blood levels of low-density lipoprotein cholesterol (LDL-C) are associated with an increased risk for atherosclerotic coronary heart disease (CHD). Atorvastatin is a statin drug that inhibits 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (the rate-limiting step of cholesterol production) and primarily lowers LDL-C levels. Atorvastatin has also been shown to significantly reduce CHD events.