Muraglitazar (proposed tradename Pargluva) is a dual

peroxisome proliferator-activated receptor agonist PPAR agonists are drugs which act upon the peroxisome proliferator-activated receptor. They are used for the treatment of symptoms of the metabolic syndrome, mainly for lowering triglycerides and blood sugar. Classification PPAR-alpha and PPAR-g ...

with affinity to

PPARα Peroxisome proliferator-activated receptor alpha (PPAR-α), also known as NR1C1 (nuclear receptor subfamily 1, group C, member 1), is a nuclear receptor protein functioning as a transcription factor that in humans is encoded by the ''PPARA'' gen ...

and

PPARγ Peroxisome proliferator- activated receptor gamma (PPAR-γ or PPARG), also known as the glitazone reverse insulin resistance receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor functioning as a tran ...

. The drug had completed

phase III clinical trial The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...

s, however in May, 2006

Bristol-Myers Squibb The Bristol Myers Squibb Company (BMS) is an American multinational pharmaceutical company. Headquartered in New York City, BMS is one of the world's largest pharmaceutical companies and consistently ranks on the ''Fortune'' 500 list of the lar ...

announced that it had discontinued further development. Data on muraglitazar is relatively sparse due to the recent introduction of this agent. One double-blind randomized clinical trial comparing muraglitazar and

pioglitazone Pioglitazone, sold under the brand name Actos among others, is an anti-diabetic medication used to treat type 2 diabetes. It may be used with metformin, a sulfonylurea, or insulin. Use is recommended together with exercise and diet. It is not re ...

found that the effects of the former were favourable in terms of

HDL-C High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are t ...

increase, decrease in total

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

apolipoprotein B Apolipoprotein B (ApoB) is a protein that in humans is encoded by the gene. Function Apolipoprotein B is the primary apolipoprotein of chylomicrons, VLDL, Lp(a), IDL, and LDL particles (LDL—commonly known as "bad cholesterol" when in refer ...

triglyceride A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''tri-'' and ''glyceride''). Triglycerides are the main constituents of body fat in humans and other vertebrates, as w ...

s and a greater reduction in HbA_1c ( ''p'' <0.0001 for all comparisons). However, the muraglitazar group had a higher all-cause mortality, greater incidence of

edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...

and

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

and more weight gain compared to the pioglitazone group. A

meta-analysis A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...

of the phase II and III clinical trials of muraglitazar revealed that it was associated with a greater incidence of

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

transient ischemic attack A transient ischemic attack (TIA), commonly known as a mini-stroke, is a minor stroke whose noticeable symptoms usually end in less than an hour. TIA causes the same Symptoms of stroke, symptoms associated with strokes, such as weakness or numbn ...

s and congestive heart failure (CHF) when compared to placebo or pioglitazone. By calling attention to adverse events made public through the FDA advisory committee process, Dr Nissen came upon a mechanism to steer FDA from the outside. This mechanism came to fruition with rosiglitazone (Avandia)and led to FDA requiring demonstration of cardiac safety for new drugs to treat type 2 diabetes. This process is described by Dr Robert Misbin in INSULIN-History from an FDA Insider, published June 1, 2020 on Amazon.

References

Abandoned drugs Oxazoles Carbamates Phenol ethers PPAR agonists {{gastrointestinal-drug-stub