Clinical Analysis of Atorvastatin Calcium, Fenofibrate, and Acipimox in the Treatment of Hypertriglyceridemia-induced Acute Pancreatitis. Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is an increasingly recognized and potentially severe form of acute pancreatitis. The effective management of HTG-AP is critical due to its association with significant morbidity and mortality. HTG-AP aims to evaluate the efficacy of atorvastatin calcium, fenofibrate, and acipimox, either individually or in combination, in the treatment of HTG-AP, providing insights into more effective management strategies. 150 HTG-AP patients admitted to the first hospital of Putian from June 2020 to December 2022 were selected. The age range of the patients included in the study was between 30 and 70 years
A study protocol to investigate if acipimox improves muscle function and sarcopenia: an open-label, uncontrolled, before-and-after experimental medicine feasibility study in community-dwelling older adults. Sarcopenia is the age-associated loss of muscle mass and strength. Nicotinamide adenine dinucleotide (NAD) plays a central role in both mitochondrial function and cellular ageing processes implicated in sarcopenia. NAD concentrations are low in older people with sarcopenia, and increasing skeletal muscle NAD concentrations may offer a novel therapy for this condition. Acipimox is a licensed lipid-lowering agent known to act as an NAD precursor. This open-label, uncontrolled, before-and-after proof-of-concept experimental medicine study will test whether daily supplementation with acipimox
Acipimox in Mitochondrial Myopathy (AIMM): study protocol for a randomised, double-blinded, placebo-controlled, adaptive design trial of the efficacy of acipimox in adult patients with mitochondrial myopathy. Mitochondrial disease is a heterogenous group of rare, complex neurometabolic disorders. Despite their individual rarity, collectively mitochondrial diseases represent the most common cause in patients with mitochondrial disease. Currently, there are no effective licensed treatments and consequently, there is an urgent clinical need to find an effective drug therapy. To investigate the efficacy of 12-week treatment with acipimox on the adenosine triphosphate (ATP) content of skeletal muscle in patients with mitochondrial disease and myopathy. AIMM is a single-centre, double blind, placebo
The impact of short-term forearm immobilization and acipimox administration on muscle amino acid metabolism and insulin sensitivity in healthy, young volunteers. The mechanisms underpinning short-term muscle disuse atrophy remain to be elucidated, but perturbations in lipid metabolism may be involved. Specifically, positive muscle non-esterified fatty acid (NEFA) balance has been implicated in the development of disuse-induced insulin and anabolic resistance. Our aim was to determine the impact of acipimox administration (i.e. pharmacologically lowering circulating NEFA availability) on muscle amino acid metabolism and insulin sensitivity during short-term disuse. Eighteen healthy individuals (age 22±1 years, BMI 24.0±0.6 kg·m) underwent 2 days of forearm cast immobilization with placebo (PLA; =9, 5M
Investigation of the clinical effects of acipimox in patients with vulnerable carotid atherosclerosis. To investigate the clinical effects of acipimox in patients with vulnerable carotid atherosclerosis. 80 patients with vulnerable carotid atherosclerosis who were admitted to the Department of Cardiology in Wuxi Second People's Hospital between February 2020 and October 2021 were enrolled in this study. All of these patients were randomly divided into an observation group ( = 40), who were given acipimox and conventional treatment, and a control group ( = 40), who were given conventional treatment. The levels of blood lipids and adiponectin (APN), the carotid intima-media thickness (IMT), the area, thickness and number of CAS, peak systolic velocities (PSV) and end-diastolic blood velocity
Impact of Acipimox Therapy on Free Fatty Acid Efflux and Endothelial Function in the Metabolic Syndrome: A Randomized Trial. Insulin resistance is associated with increased lipolysis and elevated concentrations of free fatty acids (FFA), which in turn contribute to impaired vascular function. It was hypothesized that lowering FFA with acipimox, a nicotinic acid derivative that impairs FFA efflux , would improve endothelial function, measured by flow-mediated dilation (FMD), in individuals with metabolic syndrome. A total of 18 participants with metabolic syndrome and 17 healthy controls were enrolled and treated with acipimox 250 mg orally every 6 hours or placebo for 7 days in a randomized, double-blind, crossover trial. Acipimox reduced FFA concentrations among individuals with metabolic
Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients. Glucagon-like peptide-1 (GLP-1) is an incretin hormone used therapeutically in type 2 diabetes and obesity. The interplay between ambient free fatty acids (FFAs) and GLP-1 remains unclear. Acipimox suppresses adipose tissue lipolysis via activation of the PUMA-G (also known as HCA2 and GPR109a ) receptor. To investigate whether lowering of serum FFA level with acipimox affects GLP-1 secretion. Two randomized crossover studies were performed in human subjects. Rat intestine was perfused intra-arterially and intraluminally, and l-cells were incubated with acipimox. The participants were healthy overweight subjects and hypopituitary adult patients. The overweight participants received acipimox 250
Acipimox Administration With Exercise Induces a Co-feedback Action of the GH, PP, and PYY on Ghrelin Associated With a Reduction of Peripheral Lipolysis in Bulimic and Healthy-Weight Czech Women: A Randomized Study. Anti-lipolytic drugs and exercise are enhancers of growth hormone (GH) secretion. Decreased circulating free fatty acids (FFA) have been proposed to exert ghrelin-GH feedback loop after administration of an anti-lipolytic longer-acting analog of nicotinic acid, Acipimox (OLB, 5-Methylpyrazine-2-carboxylic acid 4-oxide, molecular weight of 154.1 Da). OLB administration strongly suppresses plasma FFA during exercise. Neuroendocrine perturbations of the adipose tissue (AT), gut, and brain peptides may be involved in the etiopathogenesis of eating disorders including bulimia
Shortâ€term acipimox treatment is associated with decreased cardiac parasympathetic modulation The nicotinic acid analogue acipimox is an antilipolytic agent, which acutely inhibits lipolysis and suppresses systemic levels of free fatty acids (FFA) and improves insulin sensitivity in obese patients. These effects of acipimox are transient due to a counter-regulatory increase in growth hormone levels that reverse the antilipolytic effect of acipimox. Hypopituitary patients constitute a viable model to study the growth hormone-independent effects of acipimox and the impact of isolated changes in FFA concentrations and insulin sensitivity on parasympathetic nervous activity. The aim of the present study was to investigate if pharmacological antilipolysis with acipimox acutely affects autonomic
Effect of Dapagliflozin With and Without Acipimox on Insulin Sensitivity and Insulin Secretion in T2DM Males. To investigate the effect of lowering the plasma glucose and free fatty acid (FFA) concentrations with dapagliflozin and acipimox, respectively, on insulin sensitivity and insulin secretion in T2DM individuals. Fourteen male T2DM patients received an oral glucose tolerance test and euglycemic hyperinsulinemic clamp at baseline and were treated for 3 weeks with dapagliflozin (10 mg per day). During week 3, acipimox (250 mg four times per day) treatment was added to dapagliflozin. The oral glucose tolerance test and insulin clamp were repeated at the end of weeks 2 and 3. Dapagliflozin caused glucosuria and significantly lowered the plasma glucose concentration (by 35 mg/dL; P < .01
Metabolic Effects of Long-term Reduction in Free Fatty Acids with Acipimox in Obesity: A Randomized Trial. Increased circulating free fatty acids (FFAs) have been proposed to contribute to insulin resistance in obesity. Short-term studies have investigated the effects of acipimox, an inhibitor of hormone-sensitive lipase, on glucose homeostasis, but longer-term studies have not been performed . To test the hypothesis that long-term treatment with acipimox would reduce FFA and improve insulin sensitivity among nondiabetic, insulin-resistant, obese subjects. At an academic medical center, 39 obese men and women were randomized to acipimox 250 mg thrice-daily vs identical placebo for 6 months. Plasma lipids, insulin sensitivity, adiponectin, and mitochondrial function via assessment of the rate
Kinetics and utilization of lipid sources during acute exercise and acipimox. Overweight is associated with abnormalities of lipid metabolism, many of which are reversed by exercise. We investigated the impact of experimental antilipolysis and acute exercise on lipid kinetics and oxidation from VLDL-TG, plasma FFA, and "residual lipids" in overweight men (n = 8) using VLDL-TG and palmitate tracers in combination with muscle biopsies in a randomized, placebo-controlled design. Participants received placebo or acipimox on each study day (4 h of rest, 90 min of exercise at 50% V(O(2 max))). Exercise suppressed VLDL-TG secretion significantly during placebo but not acipimox (placebo-rest: 64.2 ± 9.4; placebo-exercise: 48.3 ± 8.0; acipimox-rest: 55.2 ± 13.4; acipimox-exercise: 52.0 ± 10.9
Evidence for a direct effect of the NAD+ precursor Acipimox on muscle mitochondrial function in humans. Recent preclinical studies showed the potential of nicotinamide adenine dinucleotide (NAD(+)) precursors to increase oxidative phosphorylation and improve metabolic health, but human data are lacking. We hypothesize that the nicotinic acid derivative acipimox, an NAD(+) precursor, would directly affect mitochondrial function independent of reductions in nonesterified fatty acid (NEFA) concentrations. In a multicenter randomized crossover trial, 21 patients with type 2 diabetes (age 57.7 ± 1.1 years, BMI 33.4 ± 0.8 kg/m(2)) received either placebo or acipimox 250 mg three times daily dosage for 2 weeks. Acipimox treatment increased plasma NEFA levels (759 ± 44 vs. 1,135 ± 97 μmol/L
Acute reduction of lipolysis reduces adiponectin and IL-18: evidence from an intervention study with acipimox and insulin. Low-grade inflammation is a feature of chronic diseases such as type 2 diabetes and lipodystrophy. It is associated with abdominal adiposity, increased levels of NEFA, hyperinsulinaemia and low adiponectin levels. However, the causal relationship between impaired metabolism and inflammation is not understood. We explored the anti-lipolytic effect of acipimox and insulin on adiponectin and adipocyte-associated cytokines in patients with lipodystrophy. In a randomised placebo-controlled crossover design using nine patients with non-diabetic, HIV-associated lipodystrophy, we assessed whether (1) overnight administration of a low dose of acipimox and/or (2) insulin-induced suppression
Short-term exercise combined with Acipimox administration induces an increase in plasma ACTH and its subsequent fall in the recovery phase in bulimic women. Free fatty acids (FFA)-adrenocorticotropin (ACTH) feedback loop between adipose tissue and the hypothalamic-pituitary centers in the brain has been suggested to be affected by the exercise and by administration of anti-lipolytic drugs. Also leptin may be affected by exercise. Dysfunction of FFA-leptin-ACTH secretion might be involved in binge eating and subsequent purging as is the case in bulimia nervosa (BN). In the present single-blind, randomized study, we explored responses of plasma ACTH, leptin and FFA concentrations to exercise (45 min, 2 W/kg of lean body mass [LBM]) with Acipimox (Aci), an anti-lipolytic nicotinic acid analog
Pharmacokinetics and bioequivalence evaluation of two acipimox tablets: a single-dose, randomized-sequence, two-way crossover study in healthy chinese male volunteers. The study was designed to compare the pharmacokinetic parameters and relative bioavailability of a newly generic acipimox 250-mg tablets (test formulation) with a branded 250-mg tablets (reference formulation). A single-dose , randomized-sequence, 2-way crossover study was conducted in 20 healthy Chinese male volunteers in the fasted state. Plasma samples were collected over 12 h after a single oral dose of 250-mg acipimox test or reference, followed by a 7-day washout period. Plasma concentrations of acipimox were analyzed by high-performance liquid chromatography. Drug And Statistical-Version 2.0 was used to calculate
The Role of Serum Free Fatty Acids in Endothelium-Dependent Microvascular Function. Elevated serum free fatty acid (FFA) concentration is associated with insulin resistance and is a hallmark of metabolic syndrome. A pathological feature of insulin resistance is impaired endothelial function. To investigate the effect of FFA reduction with either acipimox, a nicotinic acid derivative that impairs lipolysis, or salsalate, a salicylate that reduces basal and inflammation-induced lipolysis, on insulin-mediated endothelium-dependent vasodilation. This was a post hoc, combined analysis of two randomised, double-blind, placebo-controlled crossover trials. Sixteen subjects were recruited (6 with metabolic syndrome and 10 controls) and randomised to acipimox 250 mg orally every 6 h for 7 days or placebo
). Coupling between cardiac function and fatty acid concentrations, was studied on a separate day with a second scan after reduction of plasma fatty acids with acipimox. Data are Mean ± standard error. Between treatment difference (ΔT: E-I) and treatments effects (ΔE: E-WO or ΔI: I -WO) were evaluated using Students' t-test or Wilcoxon signed rank test as appropriate. Glucose concentrations were similar , fatty acids, ketone bodies and lipid oxidation increased while insulin concentrations decreased on empagliflozin compared with insulin treatment. Cardiac diastolic and systolic function were unchanged by either treatment. Acipimox decreased fatty acids with 35% at all visits, and this led to reduced cardiac diastolic (ΔT: -51 ± 22 ml/s (p < 0.05); ΔE: -33 ± 26 ml/s (ns); ΔI: 37 ± 26 (ns, p < 0.05 vs
evaluation is performed before and at the end of each treatment period.The primary endpoint is change (treatment-washout) in left ventricular peak filling rate, as assessed by cardiac MRI with and without acute lowering of plasma FFAs with acipimox. Secondary and explorative endpoints are changes in left atrial passive emptying fraction, left ventricular ejection fraction, central blood volume