Darapladib drug can protect against vision loss in diabetic patients

Researchers at Queen's University Belfast and University College London have discovered that a drug, originally developed to treat cardiovascular disease, has the potential to reduce diabetes related blindness.

According to recent WHO global estimates, 422 million people have diabetes. One of the most common complications of this disease is vision loss.  Diabetic Macular Oedema occurs in approximately 7 per cent of patients with diabetes and is one of the most common causes of blindness in the Western World. In the UK, this sight-threatening complication of diabetic retinopathy is associated with estimated health and social care costs of £116 million. The socio-economic burden will only increase with prevalence of diabetes rising by more than 50 per cent by 2030.

Queen's and UCL researchers, in partnership with  GlaxoSmithKline, found that the drug Darapladib inhibits an enzyme which is increased in people with diabetes and causes blood vessel leakage in the eye which leads to swelling of the retina and severe vision loss.

Currently, the most common treatments for patients with Diabetic Macular Oedema is an injection of a drug directly into to the eye every 4-6 weeks.  This therapy is very expensive and not effective for about half of all patients with Diabetic Macular Oedema.

The discovery by the Queen's and UCL teams demonstrates that Darapladib in form of a tablet has potential to reduce the need for monthly injections and provide protection against vision loss in a much wider group of patients with diabetes.

Speaking about the breakthrough, Professor Alan Stitt, from the Centre for Experimental Medicine at Queen's University, said: "Diabetes-related blindness is caused by high blood sugar levels damaging the blood vessels in the retina.  We have found that an enzyme called Lp-PLA2 which metabolises fats in the blood contributes to blood vessel damage and leakiness in the retina. The drug Darapladib acts as inhibitor of Lp-PLA2, and was originally developed for cardiovascular disease. Based on our break-though we are now planning a clinical trial and if successful we could soon see an alternative, pain-free and cost effective treatment for diabetic related blindness."

Dr Patric Turowski from the UCL Institute of Ophthalmology said: "With our study we show that a blood lipid produced by Lp-PLA2 constitutes a novel trigger factor in diabetic macular oedema and that use of Darapladib may not only constitute an cost-effective alternative to current DMO treatments but has the potential to be effective for patients that currently do not respond to standard treatment."

FDA Approves Eylea (aflibercept) Injection Prefilled Syringe

Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN)  announced the U.S. Food and Drug Administration (FDA)   approval the Chemistry, Manufacturing and Controls (CMC) Prior-Approval Supplement (PAS) for the Eylea (aflibercept) Injection prefilled syringe. The 2 mg, single-dose, sterilized prefilled syringe provides physicians with a new way to administer Eylea that requires fewer preparation steps compared to vials. Market supply of the Eylea prefilled syringe is expected to be available to physicians and patients this year.

"With eight pivotal Phase 3 trials and millions of injections used around the world, Eylea sets a high bar for visual acuity and safety across multiple retinal diseases, including wet age-related macular degeneration and diabetic eye diseases," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer of Regeneron. "This approval may help doctors more conveniently and efficiently deliver Eylea to appropriate patients."

The sterilized prefilled syringe offers the same medicine as the currently available Eylea, in an easier to use and administer presentation.

In the U.S., Eylea is indicated to treat neovascular (wet) age-related macular degeneration (Wet AMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME) and diabetic retinopathy (DR).

About Eylea (aflibercept) Injection

Eylea (aflibercept) Injection is a vascular endothelial growth factor (VEGF) inhibitor formulated as an injection for the eye. It is designed to block the growth of new blood vessels and decrease the ability of fluid to pass through blood vessels (vascular permeability) in the eye by blocking VEGF-A and placental growth factor (PLGF), two growth factors involved in angiogenesis. In the U.S., Eylea is the market-leading, FDA-approved anti-VEGF treatment for its approved indications and is supported by a robust body of research that includes eight pivotal Phase 3 trials.

IMPORTANT SAFETY INFORMATION

• Eylea (aflibercept) Injection is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to aflibercept or to any of the excipients in Eylea.
• Intravitreal injections, including those with Eylea, have been associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering Eylea. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately. Intraocular inflammation has been reported with the use of Eylea.
• Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with Eylea. Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with VEGF inhibitors. Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately.
• There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including Eylea. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The incidence of reported thromboembolic events in wet AMD studies during the first year was 1.8% (32 out of 1824) in the combined group of patients treated with Eylea compared with 1.5% (9 out of 595) in patients treated with ranibizumab; through 96 weeks, the incidence was 3.3% (60 out of 1824) in the Eylea group compared with 3.2% (19 out of 595) in the ranibizumab group. The incidence in the DME studies from baseline to week 52 was 3.3% (19 out of 578) in the combined group of patients treated with Eylea compared with 2.8% (8 out of 287) in the control group; from baseline to week 100, the incidence was 6.4% (37 out of 578) in the combined group of patients treated with Eylea compared with 4.2% (12 out of 287) in the control group. There were no reported thromboembolic events in the patients treated with Eylea in the first six months of the RVO studies.
• Serious adverse reactions related to the injection procedure have occurred in <0.1% of intravitreal injections with Eylea including endophthalmitis and retinal detachment.
• The most common adverse reactions (≥5%) reported in patients receiving Eylea were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and intraocular pressure increased.

INDICATIONS

Eylea (aflibercept) Injection 2 mg (0.05 mL) is indicated for the treatment of patients with Neovascular (Wet) Age-related Macular Degeneration (AMD), Macular Edema following Retinal Vein Occlusion (RVO), Diabetic Macular Edema (DME), and Diabetic Retinopathy (DR).

https://en.wikipedia.org/wiki/Aflibercept

https://www.eylea.us/

Mecamylamine may help to treat diabetic macular edema ......

We know that mecamylamine (see structure) has been used as a  ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool. It is also sometimes used as an anti-addictive drug to help people stop smoking tobacco, and is now more widely used for this application than it is for lowering blood pressure. This effect is thought to be due to it blocking α3β4 nicotinic receptors in the brain.

Now researchers from the Wilmer Eye Institute of Johns Hopkins University School of Medicine in Maryland have come up with an interesting finding from an early-stage human clinical trials. i.e.,  the drug  'mecamylamine'  was safe and had biological effects in a type of diabetic eye disease, and may offer researchers a new approach to prevent and treat diabetic macular edema. 

Diabetic macular edema is a complication of a specific region of the retina in the eye, called the macula, that develops when small blood vessels become leaky such that fluid accumulates. Without treatment, diabetic macular edema can cause vision impairment, blurriness, or blindness.

As per the claim by the researcers,  approximately 40% of the participants showed significant improvement in overall vision and/or the thickness of the retina. The treatment also showed biological effects in the retina indicating that the drug was able to gain access to the retinal vessels.

"The safety and early signals of treatment effect arising from this study may create a strong interest in the development of multiple treatment options that are affordable and can be self-administered, helping to ease the burden of healthcare delivery and compliance," said Barbara Araneo, Director of Complications Research for JDRF. ...

Ref : http://www.jdrf.org/index.cfm?fuseaction=home.viewPage&page_id=9065027A-1321-C844-137596CDA72C825B 

Experimental lipid-lowering drug improves glucose control in diabetic patients

High triglycerides -- a type of fat, or lipid, in the blood -- increase the risk of heart disease and perhaps type 2 diabetes. For the first time, it has been shown that profoundly lowering triglycerides in diabetics improves their insulin sensitivity over time, which helps them maintain healthy glucose - blood sugar -- levels. Volanesorsen, an experimental lipid-lowering medication, improved insulin sensitivity and glucose control by significantly decreasing patients' overall hemoglobin A1c -- the standard clinical measurement of blood glucose levels for diabetics -- in a new study reported by researchers from the Perelman School of Medicine at the University of Pennsylvania. The results are published online this month in Diabetes Care.

Researchers enrolled 15 adult patients with type 2 diabetes and hypertriglyceridemia who had been taking metformin - an oral medication that helps control blood sugar levels - for their diabetes. Patients were randomly assigned to two groups: one to receive volanesorsen and the other a placebo. After taking the medication for 12 weeks, researchers found that patients on volanesorsen experienced a 69 percent reduction in triglycerides, and a 57 percent improvement in whole-body insulin sensitivity. Several tests of glucose control, including hemoglobin A1c, were also significantly improved. Researchers concluded that the drop in triglycerides was strongly related to improved insulin sensitivity and improved hemoglobin A1c.

"These results prove volanesorsen to be an effective treatment method for improving insulin sensitivity, but what's most interesting, and perhaps most encouraging, is that this drug also significantly improved patients' hemoglobin A1c levels," said the study's lead co-author, Richard Dunbar, MD, an assistant professor of Cardiovascular Medicine at Penn. "In most cases, it takes many months of therapy to improve the hemoglobin A1c, so to move the needle so significantly in a fairly short time is very promising. Scientifically, these results provide important proof that profoundly lowering triglycerides improves insulin sensitivity. And clinically, the results go a step further and show that doing so improves the underlying metabolic problems enough to actually improve diabetes."

To quantify the effects of the drug, researchers used a very sophisticated test of insulin sensitivity, the hyperinsulinemic-euglycemic clamp or "the clamp," which is largely regarded as the gold standard in insulin sensitivity measurement. This technique infuses insulin at fixed rates, and infuses glucose at a varying rate to keep blood glucose constant, in order to determine how well a patient responds to insulin.

For many years, researchers had suspected that high triglycerides worsened diabetes, but there had not been powerful tool to prove this concept.

"While we were able to determine the effectiveness of this medication in a very specific group of diabetic patients, it will be important to evaluate this drug in a broader diabetic population," Dunbar said. "The next phase will be to determine clinical success in patients with type 2 diabetes on the whole range of diabetic medications or perhaps with less severe lipid problems. It will also be important to conduct longer studies, as glucose control may improve even further with longer exposures to the drug."

Several other classes of medications that profoundly lower triglycerides are also in development. If improved insulin sensitivity and improved glucose control are truly the result of lowering triglycerides, researchers suggest these other novel drugs should show the same effect.

Dunbar added, "after a long dry spell, there is a lot of activity right now for triglyceride-lowering therapies. Penn Medicine has been conducting several clinical trials evaluating this and other novel triglyceride-lowering drugs. Not only do we have a variety of very potent options emerging, we may be able to help improve glucose at the same time. Both of these developments would be great news for our patients with high triglycerides, including diabetics."

FDA Approves Trijardy XR (empagliflozin/linagliptin/metformin) for Type 2 Diabetes in Adults

In continuation of my update on empagliflozin/linagliptin/metformin 

    

The U.S. Food and Drug Administration (FDA) has approved Trijardy XR (empagliflozin/linagliptin/metformin hydrochloride extended release tablets) to lower blood sugar in adults with type 2 diabetes, along with diet and exercise. Trijardy XR provides three type 2 diabetes medicines in one pill, including Jardiance® (empagliflozin), Tradjenta® (linagliptin) and metformin hydrochloride extended release. Trijardy XR is marketed by Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company (NYSE: LLY).

"Many adults living with type 2 diabetes who are already on a treatment plan including multiple medications still struggle to keep their blood sugar under control, and may require additional agents to reach their A1C targets," said Ralph DeFronzo, M.D., professor and diabetes division chief, UT Health San Antonio. "Adding new medicines to an individual's plan can be challenging for some, which is why new treatment options that can help improve blood sugar without the burden of an increased pill count are important. In addition, type 2 diabetes is a complex disease that often requires the use of multiple antidiabetic medications to improve glycemic control. Having three different diabetes medications in a single tablet is an important advance in diabetes treatment."

In the U.S., both Jardiance and Tradjenta are once-daily tablets used along with diet and exercise to lower blood sugar in adults with type 2 diabetes. Jardiance is also approved to reduce the risk of cardiovascular death in adults with type 2 diabetes who have known cardiovascular disease. Jardiance is not for people with type 1 diabetes or for people with diabetic ketoacidosis (increased ketones in the blood or urine). Tradjenta is not for people with type 1 diabetes or for the treatment of diabetic ketoacidosis. Tradjenta has not been studied in people with a history of pancreatitis and it is unknown if using Tradjenta increases the risk of developing pancreatitis in these people. 

"We are proud to offer Trijardy XR as a new once-daily option combining three well-established medicines, including an extended-release version of metformin, the most commonly prescribed initial treatment for type 2 diabetes, Jardiance, the most prescribed SGLT2 inhibitor, and Tradjenta, the only single-dose DPP-4 inhibitor," said Mohamed Eid, M.D., M.P.H., M.H.A., vice president, Clinical Development & Medical Affairs, Cardio-Metabolism & Respiratory Medicine, Boehringer Ingelheim Pharmaceuticals, Inc. "We believe Trijardy XR has the potential to help adults with type 2 diabetes conveniently manage their treatment, especially those who are taking other medications and working on the necessary lifestyle changes."

Trijardy XR is not recommended for people with type 1 diabetes or diabetic ketoacidosis (increased ketones in the blood or urine). Trijardy XR has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at an increased risk for the development of pancreatitis while using Trijardy XR. The labeling for Trijardy XR contains a warning for lactic acidosis, a rare but serious complication that can occur due to metformin accumulation, and is common to all products containing metformin.

The FDA approval of Trijardy XR is based on two randomized open-label trials that assessed the bioequivalence of empagliflozin, linagliptin and metformin hydrochloride extended release fixed-dose combination tablets and their individual components in healthy adults. The safety profile of Trijardy XR was found to be consistent with its individual components.

"The approval of Trijardy XR reflects our commitment to the diabetes community and to innovation that addresses evolving needs," said Jeff Emmick, M.D. Ph.D., vice president, Product Development, Lilly. "We developed Trijardy XR because many people with type 2 diabetes need help managing this complex condition without adding more pills to their treatment plan. We look forward to making this new option available soon."

Trijardy XR is not for people who have severe kidney problems, end stage renal disease, or are on dialysis, have a serious condition called metabolic acidosis or diabetic ketoacidosis (increased ketones in the blood or urine), or are allergic to Jardiance, Tradjenta, metformin, or any of the ingredients in Trijardy XR. There have been postmarketing reports of acute pancreatitis, including fatal pancreatitis, in patients taking linagliptin, a component of Trijardy XR. Take careful notice of potential signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue Trijardy XR and initiate appropriate management. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using Trijardy XR.

Trijardy XR will be available in four different dosages, including: 5 mg empagliflozin/2.5 mg linagliptin/1000 mg metformin HCl extended-release; 10 mg empagliflozin/5 mg linagliptin/1000 mg metformin HCl extended-release; 12.5 mg empagliflozin/2.5 mg linagliptin/1000 mg metformin HCl extended-release; and 25 mg empagliflozin/5 mg linagliptin/1000 mg metformin HCl extended-release.

What is Trijardy XR?

Trijardy XR is a prescription medicine that contains 3 diabetes medicines, empagliflozin (JARDIANCE), linagliptin (TRADJENTA), and metformin hydrochloride. Trijardy XR can be used along with diet and exercise to lower blood sugar in adults with type 2 diabetes, and in adults with type 2 diabetes who have known cardiovascular disease when empagliflozin (JARDIANCE), one of the medicines in Trijardy XR, is needed to reduce the risk of cardiovascular death.

Trijardy XR is not for people with type 1 diabetes, or for people with diabetic ketoacidosis (increased ketones in the blood or urine).

If you have had pancreatitis (inflammation of the pancreas) in the past, it is not known if you have a higher chance of getting pancreatitis while you take Trijardy XR.

https://www.drugs.com/history/trijardy-xr.html

Cashew Seed Extract an Effective Anti-Diabetic ?

Cashew seed extract (hydroethanolic extract) shows promise as an effective anti-diabetic, according to a new study from the University of Montreal (Canada) and the Université de Yaoundé (Cameroun). The investigation analyzed the reputed health benefits of cashew tree products on diabetes, notably whether cashew extracts could improve the body's response to its own insulin.

The researchers claims that hydroethanolic extract of cashew seed (CSE) and its active component, anacardic acid (see structure), stimulated glucose transport into C2C12 myotubes in a concentration-dependent manner. Extracts of other parts (leaves, bark and apple) of cashew plant were inactive. Significant synergistic effect on glucose uptake with insulin was noticed at 100 g/mL CSE. CSE and AA caused activation of adenosine monophosphate-activated protein kinase in C2C12 myotubes after 6 h of incubation. No significant effect was noticed on Akt and insulin receptor phosphorylation. Both CSE and AA exerted significant uncoupling of succinate-stimulated respiration in rat liver mitochondria.

"Of all the extracts tested (out of leaves, bark, seeds and apples), only cashew seed extract significantly stimulated blood sugar absorption by muscle cells," says senior author Pierre S. Haddad, a pharmacology professor at the University of Montreal's Faculty of Medicine. "Extracts of other plant parts had no such effect, indicating that cashew seed extract likely contains active compounds, which can have potential anti-diabetic properties."

Researchers conclude that, activation of adenosine monophosphate-activated protein kinase by CSE and AA likely increases plasma membrane glucose transporters, resulting in elevated glucose uptake. In addition, the dysfunction of mitochondrial oxidative phosphorylation may enhance glycolysis and contribute to increased glucose uptake. These results collectively suggest that CSE may be a potential anti-diabetic nutraceutical.

Cashew tree products have long been reported to be effective anti-inflammatory agents, counter high blood sugar and prevent insulin resistance among diabetics. This study validates the traditional use of cashew tree products in diabetes and points to some of its natural components that can serve to create new oral therapies...

Ref  : http://www3.interscience.wiley.com/journal/123573729/abstract?CRETRY=1&SRETRY=0

Unexpected use of former cancer drug, Zebularine...

Researchers at Lund University have unexpectedly discovered that an old cancer drug can be used to prevent rejection of transplanted tissue. The researchers now have high hopes that their discovery could lead to new treatments for both transplant patients and patients with autoimmune diseases.

"Our group were studying the effects of the old tumour drug Zebularine, (see structure) developed in the USA in the 1960s, and by chance we discovered that it had completely unexpected effects on the immune system," says Leif Salford, Senior Professor of Neurosurgery.

"It turned out that Zebularine has the ability to subdue the reaction of the body's immune system. This could be important in situations where tissue or organs are transplanted. We also think it could be used to curb the body's attacks on its own tissue in autoimmune diseases, for instance type 1 diabetes or rheumatoid arthritis," says Dr Nittby.

In studies on animals, the researchers used rats that were made diabetic. The researchers transplanted the islets of Langerhans  cell groups in the pancreas producing insulin -- from healthy rats from another kind of rat into those with diabetes. The diabetic rats were divided into two groups; one group were treated with Zebularine and the other, the control group, did not receive any treatment. The diabetic rats that were treated with Zebularine survived for a significantly longer period than the untreated rats.

"It is very interesting that we only treated them with Zebularine for two weeks, but the effects of the treatment could be observed throughout the 90-day follow-up period.

"The findings are very exciting and are a sign that the immune system was not just generally suppressed, but that the treatment was more targeted. Neither did we see any signs of side-effects," said Dr Nittby.

The researchers are now working intensively to further refine the treatment. The next step is to teach certain cells in the immune system -- the dendritic cells -- to accept certain specific proteins using the Zebularine treatment. This would mean that the treatment could be targeted even more.

Unexpected use of former cancer drug

FDA Approves Iluvien for Diabetic Macular Edema

pSivida Corp., a leader in the development of sustained release, drug delivery products for treating eye diseases, today announced that the U.S. Food and Drug Administration (FDA) has approved Iluvien for the treatment of diabetic macular edema (DME). It is indicated for patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure (IOP). A single injection of the Iluvien micro-insert provides sustained treatment of DME for 36 months. Approximately 560,000 people in the U.S. are estimated to have clinically significant DME, the most frequent cause of vision loss in individuals with diabetes and the leading cause of blindness in young and middle-aged adults in developed countries. Iluvien is expected to be commercially available in the U.S. in early 2015.

FDA Approves Iluvien for Diabetic Macular Edema

Chinese Wolfberries (as dietary supplement) may improve vision imperfections caused by Type-2 diabetes..

Wolfberry, commercially called goji berry, is the common name for the  fruit of two very closely related species: Lycium barbarum. 

It is also known as Chinese wolfberry, mede berry, barbary matrimony vine, bocksdorn, Duke of Argyll's tea tree, Murali (in India), red medlar, or matrimony vine.  Unrelated to the plant's geographic origin, the names Tibetan goji and Himalayan goji are in common use in the health food market for products from this plant.

Marketing literature for wolfberry products including several "goji juices" suggest that wolfberry polysaccharides have extensive biological effects and health benefits, although none of these claims have been supported by peer-reviewed research.

Interestingly, now Dingbo "Daniel" Lin a researcher from Kansas State University, is studying wolfberries and their potential to improve damage to the retina. His findings show that the fruit can lower the oxidative stress that the eye undergoes as a result of type-2 diabetes.

Lin and his colleagues have found that wolfberries have high levels of zeaxanthin, lutein, polysaccharides and polyphenolics, which have been shown to improve vision, including the prevention of age-related macular degeneration and diabetic retinopathy. 

By using type-2 diabetic mice, the researchers are studying the effects of wolfberries on oxidative stress, one of the factors that occurs in diabetic retinopathy.

"I would not say that wolfberries are a medicine, but they can be used as a dietary supplement to traditional treatments to improve vision," Lin said. "Wolfberries have high antioxidant activity and are very beneficial to protect against oxidative stress caused by environmental stimuli and genetic mutations."

Ref : http://www.k-state.edu/media/newsreleases/mar10/wolfberry33010.html

Popular diabetes drug does not improve survival rates after cancer

In continuation of my update on metformin

Despite previous scientific studies that suggest diabetes drug metformin has anti-cancer properties, a new, first-of-its-kind study from Women's College Hospital has found the drug may not actually improve survival rates after breast cancer in certain patients.

The study, published in the journal Diabetes Care, failed to show an improved survival rate in older breast cancer patients with diabetes taking the drug metformin, a first-line treatment for diabetes. However, the authors caution further research is necessary to validate the study's findings.

"Metformin is a drug commonly used by diabetic patients to control the amount of glucose in their blood," said the study's lead author Dr. Iliana Lega, a research fellow at Women's College Research Institute. "Although existing scientific literature suggests that drug may prevent new cancers and death from breast cancer, our study found the drug did not significantly impact survival rates in our patients."

Scientific research has found metformin is associated with an up to 30 per cent reduction in new cancers and a reduction in tumour growth in non-diabetic breast cancer patients treated with the drug, Dr. Lega notes in the study.

To test the drug's anti-cancer properties, the authors examined 2,361 women, aged 66 or older who were treated with the drug and diagnosed with breast cancer between April 1, 1997 and March 31, 2008. The women were followed from their date of breast cancer diagnosis until their death or until March 30, 2010. The researchers found no significant statistical correlation between cumulative use of metformin and death from all causes or a significant reduction in deaths due to breast cancer.

"What makes our study so unique is that while the effects of metformin have been well documented, previous research has not examined the cumulative effects of the drug on patients, particularly breast cancer patients with diabetes," Dr. Lega said. "This is important given that diabetic patients may switch drugs over the course of their treatment."

The authors note a lack of data on body mass index, breast cancer stage and a short followup period for breast-cancer specific deaths, limit interpretation of their findings. Further research is necessary in a younger population of patients with breast cancer and diabetes.

"Understanding the effects of metformin on breast cancer patients is critical in helping address the gap in cancer outcomes in patients with and without diabetes," she added. "The findings will help physicians inform treatment plans for patients with diabetes."

Ref : http://care.diabetesjournals.org/content/early/2013/04/30/dc12-2535

Popular diabetes drug does not improve survival rates after cancer

Common Diabetes Drug Invokana (canagliflozin) May Also Shield Kidneys, Heart

In continuation of my update on canagliflozin

A common diabetes drug may also greatly reduce the odds for death from kidney failure and heart disease in diabetes patients with kidney disease, a new study finds.

  

The news on Invokana (canagliflozin) is important, experts say, because diabetes and kidney trouble so often go together.

"Diabetes is the leading cause of kidney failure worldwide, but for almost two decades there have been no new treatments to protect kidney function," noted study lead author Vlado Perkovic. He's a professor at The George Institute for Global Health at Oxford University in the United Kingdom.

"This definitive trial result is a major medical breakthrough as people with diabetes and kidney disease are at extremely high risk of kidney failure, heart attack, stroke and death," Perkovic said in a university news release. "We now have a very effective way to reduce this risk using a once-daily pill."

The research was paid for by drug company Janssen, which makes Invokana. The study involved more than 4,400 patients with diabetes and kidney disease across 34 countries. Half took Invokana and half took a "dummy" placebo pill. All of them received care for kidney disease according to current guidelines.

Those who took Invokana had a 30% lower risk of developing kidney failure, a 30% lower risk of dying from kidney failure or heart disease, a 20% lower risk of major heart events such as heart attack, stroke, or heart-related death, and a 39% lower risk of hospitalization for heart failure, the researchers reported.

The findings were published April 15 in the New England Journal of Medicine.

There was no higher risk of major side effects among those who took Invokana, according to the study, which was also due to be presented Monday at the ISN World Congress of Nephrology, in Melbourne, Australia.

Invokana is from a class of diabetes medicines known as sodium glucose transporter 2 (SGLT2) inhibitors.

Study co-author Meg Jardine, associate professor at The George Institute, said, "With 5 million people worldwide predicted to have kidney failure by 2035, this is a major breakthrough."

Two experts in diabetes and renal (kidney) care who read over the new study agreed the findings are significant.

"Upwards of 40% of end-stage renal disease patients have diabetes as the cause of their renal failure," noted Dr. Maria DeVita, chief of nephrology at Lenox Hill Hospital in New York City.

She explained that SGLT2 inhibitor medicines like Invokana work by blocking the "reuptake" of glucose within the kidney. More of this blood sugar, as well as salt, are therefore excreted harmlessly in urine instead of lingering in the kidneys where they can do damage, DeVita said.

So, Invokana "may substantially change the trajectory of kidney decline, preserving kidney function for years longer than we thought possible for the long term," DeVita said. "This is wonderful news for those with diabetic kidney disease."

Dr. Guy Mintz directs cardiovascular health at the Sandra Atlas Bass Heart Hospital in Manhasset, N.Y. He also believes the new findings are "exciting."

"With another impressive study of this family of medications, SGLT2 inhibitors should now be utilized in all type 2 diabetic patients with kidney disease and increased cardiovascular risk," as long as there are no reasons not to do so, Mintz believes.

"This is another tool in our belt to reduce progressive kidney disease and cardiac events in our type 2 diabetic population with kidney disease," he said.    

https://www.drugbank.ca/drugs/DB08907

https://en.wikipedia.org/wiki/Canagliflozin

 



Common Diabetes Drug Invokana (canagliflozin) May Also Shield Kidneys, Heart 

Sildenafil drug may effectively relieve nerve damage in men with long-term diabetes

New animal studies at Henry Ford Hospital found that sildenafil, a drug commonly used to treat erectile dysfunction, may be effective in relieving painful and potentially life-threatening nerve damage in men with long-term diabetes.   

The research targeted diabetic peripheral neuropathy, the most common complication of diabetes, affecting as many as 70 percent of patients.

The study was recently published online in PLOS ONE. Lei Wang, M.D., the Henry Ford neuroscientist who led the research, said that although numerous drugs have been shown to be effective in earlier animal experiments, most have not provided benefits in clinical trials.

"Generally, young diabetic animals with an early stage of peripheral neuropathy are used to investigate various drug treatments," Dr. Wang explains. "But patients with diabetes who are enrolled in clinical trials often are older and have advanced peripheral neuropathy.

"Failure to develop and properly evaluate treatments in the laboratory that properly reflect the target clinical population with diabetic peripheral neuropathy may contribute to the failure of clinical trials."

To mimic clinical trials in which diabetes patients have advanced peripheral neuropathy, the Henry Ford researchers chose male mice with type II diabetes that were 36 weeks old, roughly equivalent to middle age in humans.

Sildenafil drug may effectively relieve nerve damage in men with long-term diabetes

FDA Approves Revised Indication for Ozurdex for the Treatment of Diabetic Macular Edema

In continuation of my update on dexamethasone

Allergan, Inc., announced today that the U.S. Food and Drug Administration (FDA) has approved Ozurdex (dexamethasone intravitreal implant) 0.7 mg, a sustained-release biodegradable steroid implant, for the treatment of diabetic macular edema (DME). Ozurdex was originally approved in June as a treatment for DME in adult patients who have an artificial lens implant (pseudophakic) or who are scheduled for cataract surgery (phakic). Based on ongoing review of clinical data demonstrating efficacy and safety, the FDA has now approved Ozurdex for use in the general DME patient population.

FDA Approves Revised Indication for Ozurdex for the Treatment of Diabetic Macular Edema

Promising preliminary results for AKB-9778 in diabetic macular oedema

AKB-9778, a small molecule competitive inhibitor of vascular endothelial-protein tyrosine phosphatase (VE-PTP), has a good safety and efficacy profile in patients with diabetic macular oedema, suggests a preliminary dose-escalation study. 

By blocking VE-PTP, AKB-9778 promotes the activation of Tie2, a protein involved in the regulation of vascular permeability, explain the researchers. In preclinical studies, AKB-9778 has been shown to suppress vascular leakage as well as neovascularisation of the retina and choroid, they add.

In this phase Ib trial, four groups of six patients were treated with open-label AKB-9778 self-administered twice daily via subcutaneous injections at doses of 5.0 mg, 15.0 mg, 22.5 mg or 30.0 mg for 4 weeks.

Participants treated with the higher 22.5 mg and 30.0 mg doses, but not those given the 5.0 mg and 15.0 mg doses, experienced headache, dizziness and vasovagal events such as presyncope or syncope – adverse events that are consistent with the anticipated vasodilatory activity of AKB-9778, say the researchers.

“Modest decreases” in resting systolic blood pressure were also observed in the 22.5 mg and 30.0 mg groups, they report, adding that these effects and the adverse events were “transient” and “generally resolved” shortly after dosing.

At 4 weeks, best-corrected visual acuity (BCVA) improved from intake in the 15.0 mg, 22.5 mg and 30.0 mg groups; of 18 participants, 10 achieved an improvement of five to 10 letters, one improved by 11 letters and two by over 15 letters.

Moreover, seven patients who received AKB-9778 at doses of 15.0 mg or more showed decreases in study eye central subfield thickness (CST) from baseline, with reductions of over 100 μm in five patients and of 50 to 100 μm in two patients.

Promising preliminary results for AKB-9778 in diabetic macular oedema

Ancient berry could protect against diabetic retinopathy

In continuation of my update on wolfberry

Ancient berry could protect against diabetic retinopathy: The ancient Tibetan goji berry could help fight blindness caused by long-term diabetes according to studies conducted by University of Sydney researchers.

Team finds that their cancer-fighting compound fights obesity and diabetes, too

Eric Prossnitz, Ph.D., and his team hope to help 93 million obese Americans fight their fat.

In a paper published in Science Translational Medicine, they reported that G-1, a cancer-fighting compound they discovered some years ago, reduces fat in obese mice. Although G-1 is currently in phase 1 clinical trials for cancer, Prossnitz and his team are planning preclinical studies to use G-1 to fight fat in obese people.

Obesity affects 40% of adults in the United States, resulting in health conditions that include heart disease, high blood pressure, type 2 diabetes and some cancers. According to the U.S. Centers for Disease Control and Prevention, obesity and its related conditions far outweigh other causes of death. Current drugs for obesity don't effectively reduce it or have undesirable side effects.

Prossnitz and his team have been studying GPER, the G protein-coupled estrogen receptor that G-1 activates, because GPER affects certain breast cancer cells. When breast cancer drugs like tamoxifen and fulvestrant block estrogen receptors in a cell's nucleus, they also activate GPER, which is found in cell membranes.

Prossnitz's previous studies showed that GPER may play a role in resistance to tamoxifen and similar drugs, and that led him to wonder how G-1 affects non-cancerous cells when estrogen is lacking.

Estrogen is considered a female hormone, although men produce it at low levels. Low estrogen in women is a hallmark of menopause, and postmenopausal women also have higher rates of heart disease, high blood pressure, obesity and diabetes. So to understand whether G-1 might affect metabolism in postmenopausal women, Prossnitz and his team studied mice with low estrogen levels.

In their studies, low-estrogen female mice gained weight rapidly, even on a normal diet, and quickly became obese and diabetic. When the researchers treated these obese female mice with G-1, the mice lost weight and their diabetes went away.

The researchers determined that the weight loss wasn't due to the mice eating less or moving around more; it resulted from what their bodies did with the calories they ate. Instead of storing calories as fat, the mice used them as fuel.

"Their metabolism changed," Prossnitz says. "The mice showed an increased energy expenditure."

Prossnitz's team also studied male mice, which have naturally low levels of estrogen. The male mice were fed a high-fat diet, which made them obese and diabetic, and then some were treated with G-1. Although the treated mice did not lose weight, they did not gain additional weight either, like the untreated mice. More importantly, their diabetes improved.

"This result suggests that G-1 has separate effects on obesity and diabetes," Prossnitz says. "The G-1-treated male mice were metabolically healthier, even though they were still obese."

Finally, the team also fed a high-fat diet to low-estrogen female mice. These mice became obese very quickly, but just like their sisters on a normal mouse diet, they lost weight and their diabetes improved when they were treated with G-1. These results, says Prossnitz, could point to a sex difference in the effects of the drug or in the way GPER signals in the cells of males and females.

To learn about how G-1 increases energy expenditure, the team studied brown fat cells, which generate heat instead of storing excess calories as fat. What they found surprised them: when treated with G-1, the cells expended more energy.

"This fits nicely with what we saw in mice," Prossnitz says, "and suggests that G-1 may reduce obesity by targeting brown fat cells that burn extra calories."

In a future series of experiments, Prossnitz plans to study how signals from GPER induce the cellular changes that cause more energy to be used. He hopes that one day soon G-1 could revolutionize the treatment of metabolic disorders.

In the meantime, he and his team are starting the long path toward clinical trials that will test the ability G-1 to fight obesity and diabetes in people.

https://stm.sciencemag.org/content/12/528/eaau5956/tab-figures-data

Antidepressant could do double duty as diabetes drug, study shows

We know that, Paroxetine (also known by the trade names Aropax, Paxil, Pexeva, Seroxat, Sereupin) is an antidepressant drug of the SSRItype. Paroxetine is used to treat major depression, obsessive-compulsive disorder, panic disorder, social anxiety, posttraumatic stress disorder and generalized anxiety disorder in adult outpatients.

Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, now GlaxoSmithKline. Genericformulations have been available since 2003 when the patent expired.

In adults, the efficacy of paroxetine for depression is comparable to that of older tricyclic antidepressants, with fewer side effects and lower toxicity.  Differences with newer antidepressants are subtler and mostly confined to side effects. It shares the common side effects and contraindications of other SSRIs, with high rates of nausea, somnolence, and sexual side effects. Paroxetine is associated with clinically significant weight gain. Pediatric trials of paroxetine for depression did not demonstrate statistical efficacy better than placebo.

Now University of Texas Medical Branch at Galveston researchers have  discovered that the commonly used antidepressant drug paroxetine could also become a therapy for the vascular complications of diabetes...

"The future potential of this study is that we may be able to 'repurpose' paroxetine for the experimental therapy of diabetic cardiac complications," Szabo said. "We'll need to carefully characterize its safety profile in diabetic patients, but I think there's definite potential here."

Ref : http://diabetes.diabetesjournals.org/content/early/2012/12/03/db12-0789
Antidepressant could do double duty as diabetes drug, study shows

Study: Type 2 diabetic patients treated with DPP-4 linagliptin experience reductions in blood glucose levels

Data published in The Lancet showed that elderly people with Type 2 Diabetes (T2D) treated for 24 weeks with the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin, marketed by Boehringer Ingelheim and Eli Lilly and Company, experienced significant reductions in blood glucose levels (HbA1c) compared with those receiving placebo. In addition, the overall safety and tolerability profile of linagliptin was similar to placebo, with no significant difference in hypoglycaemia.

Study: Type 2 diabetic patients treated with DPP-4 linagliptin experience reductions in blood glucose levels

Avosentan lower doses for Overt Diabetic Nephropathy ?

Avosentan (see structure) is a potent, selective endothelin A  receptor blocker and there is convincing evidence that the endothelin system contributes to diabetic nephropathy and cardiovascular disease. Many groups are working with this drug.  Now researchers from Schwabing General Hospital and KfH Kidney Centre, in Munchen, Germany have come out with interesting results, as per claim by the lead researcher, Dr.Johannes Mann, the drug avosentan substantially reduces urinary protein loss in people with type 2 diabetes and kidney disease, but the drug causes serious side effects.

Avosentan at either dose (25 & 50 mg) lowered patients' urinary protein excretion by 40%-50% (compared with less than 10% in patients taking placebo), individuals taking the drug experienced a high incidence of serious, sometimes life-threatening side effects. These included complications of fluid overload such as pulmonary edema, as well as congestive heart failure. In addition, there were more deaths in the groups taking avosentan (21 and 17) than in the group taking placebo. 

Dr. Mann noted that the findings from the ASCEND trial highlight the risks and potential benefits of endothelin antagonists in kidney disease patients with proteinuria and will help investigators design future studies to test the drugs' potential. Specifically, lower doses of avosentan may generate more positive results....

Ref : Mann J.F., et. al., J Am Soc Nephrol. 2010 Feb 18.