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

Metformin more effective than sulfonylurea in controlling type 2 diabetes

In continuation of my update on Metformin

A Vanderbilt study examining the impact of the two most commonly prescribed oraldiabetes medications on the risk for heart attack, stroke and death has found the drug metformin has benefits over sulfonylurea drugs.

It was important to examine the cardiovascular impact of the more commonly used diabetes drugs after recent controversy surrounded another diabetes medication, rosiglitazone, because it was associated with an increased cardiac risk, said lead author, Christianne L. Roumie, M.D., MPH, assistant professor of Internal Medicine and Pediatrics. Smaller studies pointed to a potential advantage of taking the drug metformin but this study confirms this in a large population.

"We demonstrated that for every 1,000 patients who are using metformin for a year there are two fewer heart attacks, strokes or deaths compared with patients who use sulfonylureas. I think this reinforces the recommendation that metformin should be used as the first medication to treat diabetes," Roumie said.

The researchers looked at the charts of more than 250,000 veterans receiving care in Veterans Health Administration hospitals throughout the United States.

More...

Metformin more effective than sulfonylurea in controlling type 2 diabetes

Combination of diabetes and hypertension drugs can effectively treat cancer

In continuation of my update on metformin

  

Syrosingopine

  

                                                                        metformin

A combination of a diabetes medication and an antihypertensive drug can effectively combat cancer cells. The team of researchers led by Prof. Michael Hall at the Biozentrum of the University of Basel has also reported that specific cancer cells respond to this combination of drugs. The results of the study have now been published in "Science Advances".

Metformin is the most widely prescribed drug for the treatment of type 2 diabetes. Besides its blood sugar lowering effect, it also displays anti-cancer properties. The usual therapeutic dose, however, is too low to effectively fight cancer. The research team led by Prof. Michael Hall, at the Biozentrum of the University of Basel, has now made an unexpected discovery: The antihypertensive drug syrosingopine potentiates the anti-cancer efficacy of metformin. Apparently, this drug combination drives cancer cells to programmed "suicide".

Drug cocktail kills tumor cells

At higher doses, the antidiabetic drug inhibits the growth of cancer cells but could also induce unwanted side effects. Therefore, the researchers screened over a thousand drugs for whether they can enhance the anticancer action of metformin. A favorite emerged from this screening: Syrosingopine, an antihypertensive drug. As the study shows, the cocktail of these two drugs is effective in a wide range of cancers.

"For example, in samples from leukemia patients, we demonstrated that almost all tumor cells were killed by this cocktail and at doses that are actually not toxic to normal cells", says the first author, Don Benjamin. "And the effect was exclusively confined to cancer cells, as the blood cells from healthy donors were insensitive to the treatment."

Drugs block "juice" supply to cancer cells

In mice with malignant liver cancer, enlargement of the liver was reduced after the therapy. Also the number of tumor nodules was less - in some animals the tumors disappeared completely. A glance at the molecular processes in the tumor cells explains the drug combination's efficacy: Metformin lowers not only the blood glucose level, but also blocks the respiratory chain in the energy factories of the cell, the mitochondria. The antihypertensive drug syrosingopine inhibits, among other things, the degradation of sugars.

Thus, the drugs interrupt the vital processes which provide energy for the cell. Due to their increased metabolic activity and rapid growth, cancer cells have a particularly high energy consumption, which makes them extremely vulnerable when the energy supply is reduced.

Groundbreaking step towards clinical application

By testing a range of other compounds with the same mode of action, the scientists could demonstrate that the inhibition of the respiratory chain in the mitochondria is a key mechanism. These also reduced cancer cell growth in combination with the antihypertensive drug.

"We have been able to show that the two known drugs lead to more profound effects on cancer cell proliferation than each drug alone," explains Benjamin. "The data from this study support the development of combination approaches for the treatment of cancer patients." This study may have implications for future clinical application of combination scenarios targeting the energy needs of tumor cells.

Metformin could help leaky gut

In continuation of  my update on metformin

A team of researchers from University of California, San Diego, have successfully used gut organoids in their lab to show the effects of medications to treat conditions such as “leaky gut”. The study was titled, “The stress polarity signaling (SPS) pathway serves as a marker and a target in the leaky gut barrier: implications in aging and cancer,” and was published in the journal Life Science Alliance today..

The team found that they could use 3 dimensional gut cells in a Petri dish in the form of a gut organoids and test the drugs for their efficacy on leaky guts. These organoids can successfully recreate the molecular system within the lab including intestinal lining cells etc. These cells are normally sealed to prevent leakage. In certain disease conditions, the seals may be dysfunctional leading to leaky guts, wrote the researchers. These conditions are commonly seen in cancers and among the elderly, they explained. In this condition there may be leakage of microbes as well as vital molecules from the intestines into the abdominal cavities.

To create these organoids the team used donated intestinal cells from the patients. The intestines typically have crests and crypts with peaks and valleys. From the crypts they could isolate stem cells. These cells were used to create the three dimensional organoids within the labs, the team wrote. The stem cells grew to become four types of cells that normally are noted within the gut. These cells then rolled up to become mini guts within the Petri dishes they wrote. Now the organoids were capable of being tested.

University of California San Diego School of Medicine researchers thus used 3D models of human intestines in the petri dishes. These cells were donated by real patients suffering from leaky gut. The cells were created into 3D mini organoids so that they could mimic the real intestines. The team then found certain biomarkers that were characteristic of intestines that had the leakage problem. The team speculates that these markers could help researchers diagnose this condition early and also track the progression of the disease over a course of time.

For their study they used a commonly used diabetes medicine Metformin to try and plug the leaks within the intestinal walls. The study led by Pradipta Ghosh, MD, professor of cellular and molecular medicine at UC San Diego School of Medicine and Moores Cancer Center, and senior author Soumita Das, PhD, associate professor of pathology at UC San Diego School of Medicine, revealed that this commonly used drug could help patients with a leaky gut.

Ghosh and Das had earlier, in another study showed that a mechanism called the stress-polarity signaling pathway could help close the gaps between the cells and prevent the leakage. In that study they had also noted that the connections and bonds between the cells came apart due to the stress.

This new study revealed that Metformin may work to activate certain chemical reactions that could tighten these junctions and thus prevent the leakage. The team says that their success has been seen only in the Petri dishes on the mini organoids of the gut yet. They need to replicate it in humans to see if the drug could actually help patients with leaky gut conditions. They added however that the success of the drug in these organoids is a big step in proving that the drug could actually help. Metformin, they wrote raise the levels of a protein called occluding that can tighten the junctions between cells. If successful, this could help a large number of patients, they explained.

Ghosh said, “Lots of research is done in mice that are inbred so that they are genetically identical, all in the same cage, eating the same diet, in order to remove these variables from the studies. But lab mice are far more standardized than the same human from day to day, or patients we see in the clinics. Here, our model is a better representation of humanity. On the other hand, it also means that each organoid is its own unique experiment. We have to test many organoids to be able to make any claim, which we did in our study.” Das added, “I think you'd be hard pressed to find a disease in which systemic inflammation is not a driver. That's why, even though there are so many things we still don't know, we're excited about the broad potential this model and these findings open for developing personalized leaky gut therapeutics that target AMPK and the stress-polarity signaling pathway.”

There may be several disease conditions that lead to weakening of the bonds between the cells and the junctional cells between two intestinal cells, wrote the researchers. This leads to leakage of the molecules from within the intestines as well as leakage of microbes. This can trigger the immune system leading to a state of chronic inflammation. Inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease as well as other conditions such as liver damage, cancers, diabetes, atherosclerosis, arthritis and even dementia could be associated with leaky gut cells say researchers. Till date there have been no way this problem could be studied, let alone solved, wrote the researchers. This new study finally paves a way where the condition could be replicated in the lab and studied at its molecular level.

For this study the team took the mini organoids and opened up the rolled balls to expose the intestinal surface. Over these they used bacteria and other stressors to weaken the junctional cells and create leaky openings. Now they could study the molecular mechanisms as well as the drugs which could help tightening these bonds between the cells to prevent leakage.

https://www.life-science-alliance.org/content/3/3/e201900481

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

Metformin could serve as radiosensitizer to treat patients with stage III non-small cell lung cancer

In continuation of my update on metformin

Treating aggressive lung cancer with the diabetes drug metformin along with radiation and chemotherapy may slow tumor growth and recurrence, suggests new preliminary findings from researchers at the Perelman School of Medicine at the University of Pennsylvania being presented during an oral abstract session October 28 at the 15th World Conference on Lung Cancer.

The pre clinical and clinical results, which have set the stage for a first-of-its-kind prospective study, point to metformin as an effective radiosensitizer-a drug that makes tumor cells more sensitive to radiation therapy-to treat stage III non-small cell lung cancer (NSCLC). Because of poor local response and five-year survival rates around 15 percent in late-stage NSCLC patients, well-tolerated, combination therapies are greatly needed.

The abstract is being presented by Ildiko Csiki, MD, PhD, an assistant professor of Radiation Oncology at Penn's Abramson Cancer Center.

Metformin, the most-widely used drug for type-2 diabetes, has been shown to have anti-cancer effects on a number of cancers, including prostate and colon. It activates AMP-related pathways, leading to inactivation of mTOR and suppression of its downstream effectors, a crucial signaling pathway for proliferation and survival of cancer. However, little data exists to support its role in NSCLC. And its role as a radiosensitizer in lung cancer is even less understood.

Metformin could serve as radiosensitizer to treat patients with stage III non-small cell lung cancer

Biguanide mechanism discovered

For fifty years, one of the few classes of therapeutics effective in reducing glucose production has been the biguanides, which include phenformin and metformin, the latter the most frequently prescribed drug for type-2 diabetes. Nonetheless, the mechanism of action of biguanides remains imperfectly understood. The suggestion a decade ago that metformin reduces glucose synthesis through activation of the enzyme AMP-activated protein kinase (AMPK) has recently been challenged by genetic loss-of-function experiments. Here we provide a novel mechanism by which metformin antagonizes the action of glucagon, thus reducing fasting glucose levels. In mouse hepatocytes, metformin leads to the accumulation of AMP and related nucleotides, which inhibit adenylate cyclase, reduce levels of cyclic AMP and protein kinase A (PKA) activity, abrogate phosphorylation of critical protein targets of PKA, and block glucagon-dependent glucose output from hepatocytes. These data support a mechanism of action for metformin involving antagonism of glucagon, and suggest an approach for the development of antidiabetic drugs....

Biguanide mechanism discovered

Two drugs better than one to treat youth with type 2 diabetes, study suggests

Two drugs better than one to treat youth with type 2 diabetes, study suggests: A combination of two diabetes drugs, metformin and rosiglitazone, was more effective in treating youth with recent-onset type 2 diabetes than metformin alone, a new study has found. Adding an intensive lifestyle intervention to metformin provided no more benefit than metformin therapy alone.

Study finds no added benefit of empagliflozin alone or in combination for type 2 diabetes

In continuation of my update on Empagliflozin

Empagliflozin (trade name: Jardiance) has been approved since May 2014 for adults with type 2 diabetes mellitus in whom diet and exercise alone do not provide adequate glycaemic control. In 2014, the German Institute for Quality and Efficiency in Health Care (IQWiG) concluded in its dossier assessment that an added benefit of the drug in comparison with the appropriate comparator therapies was not proven. Partly, the drug manufacturer had presented no relevant data; partly not only the drugs, but also the therapeutic strategies differed; in addition, the indirect comparisons were based on studies unsuitable for the assessment.

The manufacturer now requested a new benefit assessment due to "new scientific findings", and submitted two dossiers: one for empagliflozin alone, and one for empagliflozin in combination with metformin. IQWiG determined in both early benefit assessments that the dossiers still contained no data and analyses relevant or suitable for the research questions. Hence an added benefit of empagliflozin alone or in combination with metformin in comparison with the appropriate comparator therapies is still not proven. The analyses of the large study EMPA-REG-Outcome additionally submitted were unsuitable for an assessment of the added benefit in Germany.

Same studies, same problems

Both the single agent and the combination of empagliflozin with metformin are approved alone or in combination with other blood-glucose lowering drugs including insulin. According to the Federal Joint Committee (G-BA), this resulted in three and four research questions respectively. The manufacturer again presented no relevant data for five of these seven research questions so that an added benefit is not proven. One study of direct comparison as well as several studies for indirect comparisons, all of which had already been cited in the dossier or in the commenting procedure in 2014, were available for the other two research questions.

The assessment of the data from the indirect comparison was incomplete with regard to content, although it had been known to the manufacturer since the first dossier assessment which patient-relevant outcomes were important. In particular, there was no information on specific adverse events for which a disadvantage of empagliflozin versus the comparator therapy was shown. The information provided on one of the indirect comparisons had the same deficiency; furthermore, there were contradictions to the clinical study reports. The second indirect comparison was not evaluable because the studies compared were not sufficiently similar and because therapeutic strategies instead of drugs were compared with one another again.

Hence there was no hint of an added benefit of empagliflozin in comparison with the appropriate comparator therapies for the single agent or for the fixed combination.

Study EMPA-REG-Outcome unsuitable for the assessment of the added benefit

Both dossiers additionally contained a description of the EMPA-REG-Outcome study used by the manufacturer to answer a question posed by the manufacturer itself, i.e. whether empagliflozin (alone or with metformin) in addition to standard treatment offers an added benefit for patients at high cardiovascular risk in comparison with standard treatment alone plus placebo.

The antidiabetic therapy in this study cannot be considered standard treatment, however: The blood-glucose lowering treatment was not escalated appropriately and the upper threshold values mentioned in guidelines were not consistently respected. And even if treatment was escalated, this was mostly done as emergency treatment, but not as part of a planned treatment expansion.

Effects in favour of empagliflozin mainly in Latin America and Asia

Moreover, marked regional differences were notable: Effects in favour of empagliflozin mainly occurred in study centres in Latin America and Asia, whereas in Europe, partly advantages and partly disadvantages of empagliflozin were shown. Finally, the study addressed neither the G-BA's research questions nor the appropriate comparator therapies specified there.

Thomas Kaiser, Head of the IQWiG Drug Assessment Department, commented on this attempt by the manufacturer to prove an added benefit for at least certain patients: "This is a wasted opportunity. It should be welcomed that studies of this size and this duration, which are therefore potentially informative, are conducted. But it was conducted with obvious deficiencies. Experts had pinned high hopes on this study, particularly as, in contrast to other large outcome studies, it appeared to produce positive results at first glance. A thorough analysis of the study and the results in European participants did not confirm this impression, however."

FDA Approves Jentadueto ((linagliptin/metformin hydrochloride)).....

In continuation of my update on linagliptin and metformin hydrochloride

U.S. Food and Drug Administration (FDA) has approved Jentadueto (linagliptin/metformin hydrochloride) tablets, a new tablet combining the dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin, and metformin. Jentadueto provides a new, single-tablet treatment option, taken twice-daily, for patients who need to control their blood sugar. Linagliptin (5 mg, once-daily) is marketed in the U.S. as Tradjenta (linagliptin) tablets....

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Phenformin decreases size of lung tumors and increases survival in mice

In continuation of my update on metformin and phenformin
In a new study in the journal Cancer Cell, Shaw and a team of scientists at the Salk Institute for Biological Studies found that phenformin, a derivative of the widely-used diabetes drug metformin, decreased the size of lung tumors in mice and increased the animals' survival. The findings may give hope to the nearly 30 percent of patients with non-small cell lung cancer (NSCLC) whose tumors lack LKB1 (also called STK11).

The LKB1 gene turns on a metabolic enzyme called AMPK when energy levels of ATP, molecules that store the energy we need for just about everything we do, run low in cells. In a previous study, Shaw, an associate professor in Salk's Molecular and Cell Biology Laboratory and researcher in the Institute's new Helmsley Center for Genomic Medicine, demonstrated that cells lacking a normal copy of the LKB1 gene fail to activate AMPK in response to low energy levels. LKB1-dependent activation of AMPK serves as a low-energy checkpoint in the cell. Cells that lack LKB1 are unable to sense such metabolic stress and initiate the process to restore their ATP levels following a metabolic change. As a result, these LKB1-mutant cells run out of cellular energy and undergo apoptosis, or programmed cell death, whereas cells with intact LKB1 are alerted to the crisis and re-correct their metabolism.

"The driving idea behind the research is knowing that AMPK serves as a sensor for low energy loss in cells and that LKB1-deficient cells lack the ability to activate AMPK and sense energy loss," says David Shackelford, a postdoctoral researcher at Salk who spearheaded the study in Shaw's lab and is now an assistant professor at UCLA's David Geffen School of Medicine.

That led Shaw and his team to a class of drugs called biguanides, which lower cellular energy levels by attacking the power stations of the cell, called mitochondria. Metformin and phenformin both inhibit mitochondria; however, phenformin is nearly 50 times as potent as metformin. In the study, the researchers tested phenformin as a chemotherapy agent in genetically-engineered mice lacking LKB1 and which had advanced stage lung tumors. After three weeks of treatment, Shaw and his team saw a modest reduction in tumor burden in the mice.

Ref : https://www.cell.com/cancer-cell/abstract/S1535-6108%2812%2900518-1

Phenformin decreases size of lung tumors and increases survival in mice

Takeda Receives FDA Approval for Kazano (alogliptin and metformin) for Type 2 Diabetes

Takeda Pharmaceuticals U.S.A., Inc. today announced that the United States (U.S.) Food and Drug Administration (FDA) has approved Kazano (alogliptin and metformin HCl) for the treatment of type 2 diabetes in adults as adjuncts to diet and exercise. 

Kazano contains alogliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i) that is designed to slow the inactivation of incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide). Kazano combines alogliptin with metformin HCl, a widely used anti-diabetes medication, in a single tablet.

The most common adverse events (greater than or equal to 4%) reported with alogliptin include nasopharyngitis, headache and upper respiratory tract infection. Common adverse events (greater than or equal to 4%) reported with Kazano include upper respiratory tract infection, nasopharyngitis, diarrhea, hypertension, headache, back pain and urinary tract infection.

Takeda is committed to providing type 2 diabetes patients with treatment options that help address their needs, and is planning to commercially launch Kazano in the summer of 2013.

Takeda's consolidated financial statements for the 2012 fiscal year will not be impacted by the FDA approvals.

Takeda Receives FDA Approval for Kazano (alogliptin and metformin) for Type 2 Diabetes

New clinical study to evaluate inexpensive drug to prevent type 1 diabetes

 

In continuation of my update on metformin

New trial aims to prevent type 1 diabetes

A clinical study evaluating a new hypothesis that an inexpensive drug with a simple treatment regimen can prevent type 1 diabetes will be launched in Dundee tomorrow.

The autoimmune diabetes Accelerator Prevention Trial (adAPT) is led by Professor Terence Wilkin, of the University of Exeter Medical School, with support from colleagues at the University of Dundee and NHS Tayside. It will be launched at Ninewells Hospital, Dundee, on Tuesday, 19th April.

Initial funding of $1.7 million is being provided by JDRF, the leading global organisation backing type 1 diabetes research. The study aims to contact all 6,400 families in Scotland affected by the condition, with a view to expanding into England at a later date. Children aged 5 to 16 who have a sibling or parent with type 1 diabetes will be invited for a blood test to establish whether they are at high risk of developing the disease. If so, they will be invited to take part in the trial.

Researchers will then examine the impact of administering metformin, the world's most commonly prescribed diabetes medicine, to young people in the high-risk category. If successful, the large-scale trial could explain why the incidence of type 1 diabetes has risen five-fold in the last 40 years, and provide a means of preventing it.

Researchers have previously hypothesised that type 1 diabetes is an autoimmune disease caused by a faulty immune system which attacks and destroys insulin-producing beta cells in the pancreas. Clinical trials have tried drugs that supress the immune system to attempt to subdue the attack, but the results have so far been disappointing.

The Accelerator Prevention Trial is the first to test an alternative explanation for type 1 diabetes, and is based on the accelerator hypothesis, proposed in 2001 by Professor Wilkin.

This hypothesis theorises that autoimmunity occurs as a response to damaged beta cells. It believes that beta cells, stressed by being made to work too hard in a modern environment, send out signals that switch on the immune system. adAPT will test whether metformin, which is known to protect the beta cells from stress, can stop the immune response that goes on to destroy them.

Professor Wilkin said, "We still have no means of preventing type 1 diabetes, which, at all ages, results from insufficient insulin. We all lose beta cells over the course of our lives, but most of us have enough for normal function.

"However, if the rate of beta cell loss is accelerated, type 1 diabetes develops, and the faster the loss, the younger the onset of the condition. The accelerator hypothesis talks of fast and slow type 1 diabetes - beta cell loss which progresses at different rates in different people, and appears at different ages as a result."

New use of old drugs (Metformin & AICAR ) in treating hepatitis C...

In continuation of my update on Metformin...

Researchers from  University of Leeds have found drugs such as antidiabetic  drug  Metformin  (right  structure)  and                AICAR, (5-Amino-4-imidazole carboxamide ribonucleotide) below right structure) used to combat obesity, can prevent the hepatitis C virus from replicating in the body.

Drugs such as Metformin and AICAR work by stimulating an enzyme called AMP kinase (AMPK) which regulates energy within our cells,  the very enzyme that hepatitis C virus represses to enable it to replicate. As per the claim by the researchers, the hepatitis C virus switches off AMPK so that the cell continues production of lipids and membranes, both of which are vital to its survival. 

AMPK's usual function is to conserve the energy balance in cells (it does by temporarily shutting down the production of lipids (fats) and membranes) when it senses an increase in energy requirements. Researchers  claim that, when a cell becomes infected by a virus,  AMPK gets activated and  shuts down certain functions of the cell temporarily until the cell's energy is rebalanced. 

Building on this finding, the research team were able to examine how cells would react when treated with common drugs that stimulate AMPK. They found that in infected cells, the drugs were able to halt virus replication, enabling cells to clear the infection...

"We're very excited about these findings," says Professor Mark Harris from the University's Faculty of Biological Sciences. "These drugs are already on the market, and whilst substantial clinical trials still need to take place before they can be used to treat hepatitis C infection, we think it could be an enormous step forward in the battle against the virus."  ....

Ref : http://www.leeds.ac.uk/news/article/825/new_use_for_old_drugs_in_treating_hepatitis_c?research

Metformin may protect against liver cancer

In continuation of my update on Metformin

Metformin may protect against liver cancer: Metformin, a widely used, well-tolerated drug prescribed for patients with diabetes, may protect against liver cancer, according to a new study.

FDA Approves Jentaduet ((sitagliptin and metformin hydrochloride (HCl) )...

In continuation of my update on sitagliptin and metformin hydrochloride (HCl)

U.S. Food and Drug Administration (FDA) approved JANUMET^® XR    ((sitagliptin and metformin hydrochloride (HCl) ) extended-release) tablets, a new treatment for type 2 diabetes that combines sitagliptin, which is the active component of JANUVIA^® (sitagliptin), with extended-release metformin. JANUMET XR provides a convenient once-daily treatment option for healthcare providers and patients who need help to control their blood sugar.

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Is Okra Good for Diabetes?

According to a handful of recent studies, okra may reduce symptoms of diabetes - a group of diseases that includes type 1 diabetes, type 2 diabetes, and gestational diabetes.

 

Diabetes claimed the lives of 75,578 Americans in 2013, according to the United States Centers for Disease Control and Prevention (CDC). In 2014,8.5 percent of adults worldwide had the condition, the World Health Organization (WHO) report. By 2030, diabetes may be the seventh leading cause of death.

A number of factors increase a person's risk of developing diabetes, including a family history of the disease. Lifestyle factors also play a role, so doctors routinely recommend diet changes and increased exercise to reduce blood sugar levels.

Okra may help reduce blood sugar levels in some people with diabetes. Research into the effects of this seedy vegetable is still in the early stages, but the results are promising.

Okra thrives in temperate climates, producing large hibiscus-like flowers that eventually give rise to green seed pods. It is a member of the mallow family, which includes a number of other popular plants, including hibiscus, cocoa, and cotton.

Scientifically known as Abelmoschus esculentus, okra may have been grown as long ago as 2000 BCE in Egypt.

Okra's flavor is mild, and the entire seed pod can be eaten. This vegetable-like fruit also has a long history in traditional medicine.

Kew Royal Botanic Gardens report that in Eastern traditional medicine, okra leaves and fruit were used as pain relievers, moisturizers, and to treat urinary disorders. In Congolese medicine, okra is used to encourage a safe delivery during childbirth.

Can okra help with symptoms of diabetes?

Diabetes can often be well-managed with increasing a hormone called insulin and other medical therapies. However, some people with diabetes wish to avoid regular insulin injections. Others experience blood sugar dips and other unpleasant side effects, and diabetes medications do not work for everyone.

The possibility that a readily available seed pod could help control diabetes is an exciting one. But there is no evidence yet that okra can cure diabetes. So far, the research on okra has only looked at its effects on animals. Human bodies are similar to animals, but not all research on animals has worked out in humans.

Increased absorption of sugar by muscles

A 2005 study published in Planta Medica investigated the effects of okra on rats with diabetes. A substance called myricetin is present in okra and some other foods, including red wine and tea.

Researchers isolated myricetin from okra, then administered it to the rat. The treatment increased absorption of sugar in the rats' muscles, lowering their blood sugar.

A 2012 Food Science and Human Wellness review points to a number of other laboratory and animal studies that have linked myricetin to lower blood sugar. The study argues that myricetin may also reduce other risk factors for diabetes.

Reduction in blood sugar spikes after eating

A 2011 study published in ISRN Pharmaceutics found a link between okra and decreased blood sugar spikes after eating.

Researchers fed rats liquid sugar as well as purified okra through a feeding tube. Rats who consumed the okra experienced a reduction in blood sugar spikes after feeding. The study's authors think this is because the okra blocked the absorption of sugar in the intestines.

The study also explored possible interactions between okra and metformin, a drug that can reduce blood sugar in type 2 diabetes. Okra appeared to also block absorption of metformin. This suggests that okra could reduce the effectiveness of metformin, and should therefore not be eaten at the same time as the drug.

Lower blood sugar levels

A 2011 study published in the Journal of Pharmacy and Bioallied Sciences points to a link between eating okra and lower blood sugar. The researchers allowed the blood sugar of rats with diabetes to stay level for 14 days. They then gave the rats powdered okra peel extracts and seeds dosages of up to 2,000 milligrams per kilogram of body weight.

There were no poisonous effects linked with these relatively high doses of okra. The rats that ate okra had reduced blood sugar levels after up to 28 days of eating okra. The study ended on day 28, so it is unclear if the effects on blood sugar levels would have lasted longer.

Considerations for using okra

Few studies have linked okra to negative side effects, but some negative side effects are possible:

• Okra may make the drug metformin less effective.
• Okra is high in substances known as oxalates. Oxalates may increase the risk of kidney stones in people vulnerable to kidney stones.
• Okra can contain bacteria, pesticides, and other dangerous substances if it is not thoroughly washed. People should never consume rotten okra, frozen okra that is past its expiration date, or okra that has not been thoroughly washed.
• People with an okra allergy should not consume okra. Those with an allergy to other plants in the mallow family, such as hibiscus or cotton, may also be allergic to okra.
• Even if okra proves to be ineffective in fighting diabetes, it remains a safe snack for people with diabetes. A single serving of 100 grams contains just 30 calories, but offers a number of nutritional benefits:
  • Okra contains no saturated fats or cholesterol
  • Okra is rich in fiber, containing 9 percent of the recommended daily value (RDV)
  • Okra contains 8 percent of the RDV of calcium, 43 percent of the RDV of manganese, 10 percent of the RDV of iron and copper, and 44 percent of the RDV of vitamin K
  Okra is rich in protective substances known as antioxidants, including myricetin. According to the National Center for Complementary and Integrative Health, antioxidants may reduce oxidative stress, a process that damages cells in the body. Oxidative stress plays a role in the development of diabetes, as well as diseases such as:
  • Parkinson's disease
  • Alzheimer's disease
  • Cataracts
  • Macular degeneration
  • Heart and blood vessel disease
  • Cancer
  In addition to its antioxidant benefits, okra may also reduce tiredness. A 2015 study published in Nutrients found that substances found in okra seeds known as polyphenols and flavonoids could reduce fatigue.

Research explains action of drug that may slow aging, related disease

Rapamycin, an antibiotic and immunosuppressant approved for use about 15 years ago, has drawn extensive interest for its apparent ability at least in laboratory animal tests -- to emulate the ability of dietary restriction in helping animals to live both longer and healthier.

However, this medication has some drawbacks, including an increase in insulin resistance that could set the stage for diabetes. The new findings, published in the Journals of Gerontology: Biological Sciences, help to explain why that happens, and what could be done to address it. They suggest that a combination of rapamycin and another drug to offset that increase in insulin resistance might provide the benefits of this medication without the unwanted side effect.

"This could be an important advance if it helps us find a way to gain the apparent benefits of rapamycin without increasing insulin resistance," said Viviana Perez, an assistant professor in the Department of Biochemistry and Biophysics in the OSU College of Science.

"It could provide a way not only to increase lifespan but to address some age-related diseases and improve general health," Perez said. "We might find a way for people not only to live longer, but to live better and with a higher quality of life."

Age-related diseases include many of the degenerative diseases that affect billions of people around the world and are among the leading causes of death: cardiovascular disease, diabetes, Alzheimer's disease and cancer. Laboratory mice that have received rapamycin have reduced the age-dependent decline in spontaneous activity, demonstrated more fitness, improved cognition and cardiovascular health, had less cancer and lived substantially longer than mice fed a normal diet.

Rapamycin, first discovered from the soils of Easter Island, or Rapa Nui in the South Pacific Ocean, is primarily used as an immunosuppressant to prevent rejection of organs and tissues. In recent years it was also observed that it can function as a metabolic "signaler" that inhibits a biological pathway found in almost all higher life forms --     the  ability to  sense when  food  has
been eaten, energy is available and it's okay for cell proliferation, protein synthesis and growth to proceed.

Called mTOR in mammals, for the term "mammalian target of rapamycin," this pathway has a critical evolutionary value -- it helps an organism avoid too much cellular expansion and growth when energy supplies are insufficient. That helps explain why some form of the pathway has been conserved across such a multitude of species, from yeast to fish to humans.

"Dietary restriction is one of the few interventions that inhibits this mTOR pathway," Perez said. "And a restricted diet in laboratory animals has been shown to increase their lifespan about 25-30 percent. Human groups who eat fewer calories, such as some Asian cultures, also live longer."
Aside from a food intake in laboratory mice that's about 40 percent fewer calories than normal, however, it's been found that another way to activate this pathway is with rapamycin, which appears to have a significant impact even when used late in life. Some human clinical trials are already underway exploring this potential.

A big drawback to long-term use of rapamycin, however, is the increase in insulin resistance, observed in both humans and laboratory animals. The new research identified why that is happening. It found that both dietary restriction and rapamycin inhibited lipid synthesis, but only dietary restriction increased the oxidation of those lipids in order to produce energy.

Rapamycin, by contrast, allowed a buildup of fatty acids and eventually an increase in insulin resistance, which in humans can lead to diabetes. However, the drug metformin can address that concern, and is already given to some diabetic patients to increase lipid oxidation. In lab tests, the combined use of rapamycin and metformin prevented the unwanted side effect.

"If proven true, then combined use of metformin and rapamycin for treating aging and age-associated diseases in humans may be possible," the researchers wrote in their conclusion.

This work was supported by the National Institutes of Health. Collaborators included researchers from Oklahoma University Health Science Center, the Oklahoma City VA Medical Center, University of Michigan-Flint, and South Texas Veterans Health Care System.

"There's still substantial work to do, and it may not be realistic to expect with humans what we have been able to accomplish with laboratory animals," Perez said. "People don't live in a cage and eat only the exact diet they are given. 

Nonetheless, the potential of this work is exciting."

Research explains action of drug that may slow aging, related disease