Olbetam (acipimox) / Pfizer - LARVOL DELTA

Ketones, SGLT2, HFrEF (clinicaltrials.gov) - P1 | N=71 | Suspended | Sponsor: The University of Texas Health Science Center at San Antonio | Recruiting ➔ Suspended

Trial suspension • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Type 2 Diabetes Mellitus

Burns results in profound muscle protein wasting in Sprague Dawley rats that is not resolved using the lipolysis inhibitor, acipimox. (PubMed, PLoS One) - "In a rodent model of burns, the loss of muscle mass primarily occurs due to the acceleration of muscle proteolysis, independent of any change in muscle lipid content."

Journal • Preclinical • Targeted Protein Degradation • Thermal Injury

Superimposition of increased Beta Oxidation due to Insulin deficiency is the principal molecular mechanism of diabetic ketoacidosis: A proportional hazard model (ESPE-ESE 2025) - "This can be blocked by anti-lipolysis agents such as Nicotinic acid or Acipimox. Increased activity of ATGL, HSL augmented by loss of inhibition of Perilipin-1 causes high load of Acetyl-CoA within the mitochondria that overrides its clearing potential. Acids leak out of it and the cytoplasm has no enzymatic weapon to counteract it. Extrusion of acid into the circulation re-established cytoplasmic milieu at the expense of generalized acidity."

Infectious Disease • Metabolic Disorders

Acipimox mitigates depression like behavior following high fat rich diet in rats. (PubMed, Brain Res Bull) - "In conclusion, HFRD-induced behavioral deficits (depression like behavior) mitigated by ACPX through its antioxidant, anti-inflammatory, and neuromodulatory properties. It is recommended that use of ACPX could be helpful for HFRD-induced behavioral impairment i.e. depression."

Journal • Preclinical • CNS Disorders • Depression • Inflammation • Mood Disorders • Psychiatry

SAFETY AND EFFICACY OF ACIPIMOX IN COMBINATION WITH STATINS IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION AND ELEVATED TRIGLYCERIDE LEVELS - Tianshu Gu (ACC 2025) - "The addition of acipimox to statin therapy shows a significant reduction in the risk of MACCE and NACE within the first year in AMI patients with elevated triglyceride levels."

Clinical • Combination therapy • Cardiovascular • Myocardial Infarction

Effect of acipimox on skeletal muscle biochemistry, structure and function in older people with probable sarcopenia: an experimental medicine study. (PubMed, Geroscience) - "Participants received acipimox 250 mg orally (twice or thrice daily according to creatinine clearance) + aspirin 75 mg daily (to prevent facial flushing) for 4 weeks. Although the study protocol was feasible and well tolerated, acipimox did not improve skeletal muscle NAD concentration, biochemical markers or physical function in people with probable sarcopenia. gov Identifier: ISRCTN (ISRCTN87404878)."

Journal • Sarcopenia

SSY Group Limited provides update on its product development [Google translation] (Zonebourse) - "The Board of Directors of SSY Group Limited announced that the Group has obtained approval for the production and registration of Tranexamic Acid Tablets (0.5g) from the National Medical Products Administration of China (the 'NMPA'), which is a Type 4 chemical drug, deemed to have passed the consistency assessment and the third such approval for PRC entities. Tranexamic Acid Tablets are mainly used to treat various types of bleeding caused by acute or chronic, localized or systemic primary hyperfibrinolysis. The Board of Directors is also pleased to announce that the Group has obtained approval for the production and registration of Acipimox Capsules (0.25g) from the NMPA, which is a Type 4 chemical drug, deemed to have passed the consistency assessment and the fourth such approval for PRC entities. Acipimox Capsule is mainly used to reduce triglyceride levels in patients who do not respond adequately to other treatments (such as statins or fibrates)."

China approval • Dyslipidemia • Women's Health

Co-Feedback Action of Growth Hormone, PP and PYY on Ghrelin in Bulimia (clinicaltrials.gov) - P2 | N=24 | Enrolling by invitation | Sponsor: Charles University, Czech Republic | Trial completion date: Dec 2023 ➔ Dec 2026

Trial completion date • Bulimia

The Role of Serum Free Fatty Acids in Endothelium-Dependent Microvascular Function. (PubMed, Endocrinol Diabetes Metab) - P2/3 | "Short-term reduction of FFA concentration does not improve insulin-stimulated vasodilation in patients with metabolic syndrome."

Clinical • Journal • Inflammation • Metabolic Disorders

Nicotinic acid improves mitochondrial function and associated transcriptional pathways in older inactive males. (PubMed, Transl Exerc Biomed) - "In a double-blind, randomised, placebo-controlled design, 18 sedentary yet otherwise healthy older (65-75 y) males were assigned to 2-weeks of NA (acipimox; 250 mg × 3 daily, n=8) or placebo (PLA, n=10) supplementation...NAD+-specific pathways (e.g., de novo NAD+ biosynthetic processes) and genes (e.g., NADSYN1) were uniquely regulated by NA. NA might be an effective strategy for improving ageing muscle mitochondrial health."

Journal • Inflammation • SDHB

Evaluation of Clinical Variables Affecting Myocardial Glucose Uptake in Cardiac FDG PET. (PubMed, Diagnostics (Basel)) - "Among several clinical variables, BMI and HbA1c levels were related to myocardial glucose uptake. A prospective study would be needed to examine whether a protocol that additionally considers BMI and HbA1c levels is necessary for the current cardiac FDG PET protocol."

FDG PET • Journal • Cardiovascular • Coronary Artery Disease • Genetic Disorders • Heart Failure • Obesity

Integrating myocardial metabolic imaging and stress myocardial contrast echocardiography to improve the diagnosis of coronary microvascular diseases in rabbits. (PubMed, Quant Imaging Med Surg) - "In this study, we established five distinct pretreatment groups, each consisting of nine male rabbit: a fasted group, a nonfasted group, a sugar load group, an acipimox group, and a combination group of nonfasted rabbits administered insulin...Our study demonstrated the feasibility of a simple premedication approach involving free feeding and intravenous insulin in producing high-quality gated heart 18F-FDG PET/CT images in adult male New Zealand white rabbits. This technique holds considerable potential for ischemic heart disease research in rabbits and can enhance CMVD diagnosis via the comprehensive assessment of myocardial metabolism and perfusion."

Journal • Preclinical • Cardiovascular • Coronary Artery Disease • Heart Failure

Catecholamine-Induced Adipose Lipolysis Drives Hepatic Steatosis in Pnpla3I148M Knockin Mice (ADA 2024) - "Acipimox, an inhibitor of WAT lipolysis, similarly had no effect on WT hepatic steatosis and markedly decreased hepatic triglyceride in Pnpla3I148M mice (WT: VEH 46 ± 5 mg/g; ACI 49 ± 10 mg/g... WAT catecholamine responsiveness is increased in Pnpla3I148M mice contributing to hepatic steatosis in these mice. As human hepatic triglyceride biosynthesis is strongly weighted towards esterification of preformed fatty acids from extrahepatic sources, this biology may contribute to the increased susceptibility to fatty liver seen in patients with the PNPLA3I148M mutation."

Preclinical • Metabolic Disorders • Obesity • PNPLA3 • WT1

Electronic-cigarette Exposure Induces Hyperglycemia With A Fibrotic Phenotype In Skeletal Muscle In Mice Subjected To A High-fat Diet (ENDO 2024) - "These harmful changes in the liver and heart are prevented by the lipolysis inhibitor Acipimox (Acip)...These findings suggest the detrimental effects of e-cigarettes on glycemia and SkM health in mice, with implications for long-term health outcomes, particularly among obese individuals and e-cigarette users. Further research is necessary for understanding these adverse effects and promoting youth health.GRANT SUPPORT: U54MD007598, SC2GM135127, U54MD007598-14S2, PR190942, DA050723, and R25DA050723 grants."

Late-breaking abstract • Preclinical • Diabetes • Fibrosis • Genetic Disorders • Immunology • Obesity • IGF1 • PAX7

Acipimox Normalizes Pro-inflammatory Effects Of Electronic Cigarettes And High Fat Diet On Adipose Tissue. (ENDO 2024) - "Abstract is embargoed at this time."

Late-breaking abstract

Clinical Analysis of Atorvastatin Calcium, Fenofibrate, and Acipimox in the Treatment of Hypertriglyceridemia-induced Acute Pancreatitis. (PubMed, Altern Ther Health Med) - "The patients were grouped: atorvastatin calcium, acipimox, fenofibrate, fenofibrate + Atorvastatin calcium, fenofibrate + acipimox, and no drug. Moreover, this study provides valuable insights into the management of HTG-AP and suggests that lipid-lowering agents, such as atorvastatin calcium and fenofibrate, play a crucial role in the treatment of this condition. However, further research is needed to explore the optimal dosages, treatment durations, and potential side effects of these medications in HTG-AP patients."

Journal • Dyslipidemia • Gastrointestinal Disorder • Hypertriglyceridemia • Hypotension • Infectious Disease • Inflammation • Pain • Pancreatitis • CRP

Structure-guided engineering of biased-agonism in the human niacin receptor via single amino acid substitution. (PubMed, Nat Commun) - "Here, we present cryo-EM structures of the GPR109A in complex with dyslipidemia drugs, niacin or acipimox, non-flushing agonists, MK6892 or GSK256073, and recently approved psoriasis drug, monomethyl fumarate (MMF). These structures elucidate the binding mechanism of agonists, molecular basis of receptor activation, and insights into biased signaling elicited by some of the agonists. The structural framework also allows us to engineer receptor mutants that exhibit G-protein signaling bias, and therefore, our study may help in structure-guided drug discovery efforts targeting this receptor."

Journal • Dermatology • Dyslipidemia • Immunology • Metabolic Disorders • Psoriasis

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. (PubMed, BMJ Open) - "Sixteen participants aged 65 and over with probable sarcopenia will receive acipimox 250 mg and aspirin 75 mg orally daily for 4 weeks, with the frequency of acipimox administration being dependent on renal function. Acipimox feasibility study Clinical Trial Protocol V.2 2/11/21. The ISRCTN trial database (ISRCTN87404878)."

Journal • CNS Disorders • Sarcopenia

Ketones, SGLT2, HFrEF (clinicaltrials.gov) - P1 | N=71 | Recruiting | Sponsor: The University of Texas Health Science Center at San Antonio | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Type 2 Diabetes Mellitus

Ketones, SGLT2, HFrEF (clinicaltrials.gov) - P1 | N=71 | Not yet recruiting | Sponsor: The University of Texas Health Science Center at San Antonio

New P1 trial • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Type 2 Diabetes Mellitus

The impact of forearm immobilization and acipimox administration on muscle amino acid metabolism and insulin sensitivity in healthy, young volunteers. (PubMed, Am J Physiol Endocrinol Metab) - "Disuse-induced insulin resistance is accompanied by early signs of negative net muscle amino acid balance, which is driven by accelerated muscle amino acid efflux. Acutely elevated NEFA availability worsened muscle insulin resistance without affecting amino acid kinetics, suggesting increased muscle NEFA uptake may contribute to inactivity-induced insulin resistance but does not cause anabolic resistance."

Journal • Metabolic Disorders • Muscular Atrophy

The role of empagliflozin-induced metabolic changes for cardiac function in patients with type 2 diabetes. A randomized cross-over magnetic resonance imaging study with insulin as comparator. (PubMed, Cardiovasc Diabetol) - P4 | "Despite significant metabolic differences, cardiac function did not differ on empagliflozin compared with insulin treatment. Impaired cardiac function during acipimox treatment, could suggest greater cardiac reliance on lipid metabolism for proper function during empagliflozin treatment in patients with type 2 diabetes."

Journal • MRI • Cardiovascular • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Can the Health Benefits of a Walking-based Exercise Programme be Enhanced by Co-ingestion of a Lipid-lowering Drug? (clinicaltrials.gov) - P=N/A | N=15 | Completed | Sponsor: Liverpool John Moores University | Suspended ➔ Completed | N=34 ➔ 15 | Trial primary completion date: Dec 2022 ➔ Jul 2023

Enrollment change • Trial completion • Trial primary completion date • Metabolic Disorders

Structural insights into ligand recognition and selectivity of the human hydroxycarboxylic acid receptor HCAR2. (PubMed, Cell Discov) - "Here, we report four cryo-EM structures of human HCAR2-Gi1 complexes with or without agonists, including the drugs niacin (2.69 Å) and acipimox (3.23 Å), the highly subtype-specific agonist MK-6892 (3.25 Å), and apo form (3.28 Å)...In addition, the key residues that determine the ligand selectivity between the HCAR2 and HCAR3 are also illuminated. Our findings provide structural insights into the ligand recognition, selectivity, activation, and G protein coupling mechanism of HCAR2, which shed light on the design of new HCAR2-targeting drugs for greater efficacy, higher selectivity, and fewer or no side effects."

Journal • Cardiovascular • CNS Disorders • Immunology • Metabolic Disorders • Oncology

Acipimox Does Not Improve Endothelial Function and Insulin-Stimulated Vasodilation in Patients With Metabolic Syndrome (AHA 2023) - P2/3 | "Acipimox did not improve insulin sensitivity and had no effect on microvascular endothelial dysfunction assessed by insulin-stimulated FBF. This suggests that FFA modulation does not reverse microvascular dysfunction in patients with metabolic syndrome."

Clinical • Metabolic Disorders