New type 2 diabetes treatments.

Scientists Hunting for Breakthrough Diabetes Treatments

Reading Time: 10 minutes. >>

Summary: Recently pharmaceutical firms have released new diabetes treatments, including one in the past week. Moreover, a promising new therapy that attacks the root cause of type 2 diabetes is in the development pipeline. [This article first appeared on the LongevityFacts.com website. Author: Brady Hartman. ]

The CDC recently shocked the public when they reported that 40% of Americans walking around today would develop type 2 diabetes.

Many people develop type 2 diabetes as they age because their body’s response to insulin – the hormone that controls sugar levels – gets weaker.

Fortunately, scientists have discovered new treatments for the disease and have more in the pipeline. One such drug, ertugliflozin (brand name Steglatro) was released less than a week ago.

Moreover, researchers at UCSD are developing a promising new therapy that attacks type 2 diabetes at its cellular roots.

Furthermore, doctors have developed a medication maintenance program, which can help prevent type 2 diabetics from health-robbing complications such as blindness, heart and kidney disease, and peripheral vascular disease.

There is also hope for type 1 diabetics, as scientists are working on improved insulin delivery devices, replacing damaged pancreases with stem cell-derived islet cells and the novel ‘pancreas in a box‘ that may restore normal insulin regulation.

Type 2 Diabetes Epidemic

Diabetes has been a documented human disorder for millennia, but only in recent decades has it developed into an epidemic. Mentions of the condition in ancient medical texts are rare. The primary drivers of the worldwide epidemic are the increasing age of the population, and the obesity epidemic, fed by the growing global adoption of the Western diet.

Obesity – the most significant risk factor for type 2 diabetes – is increasing rapidly as a global epidemic which threatens to offset the many medical advances that increase longevity. The Western diet – high in fat, sugar, and calories – is to blame for the so-called ‘diabesity’ phenomenon, named for the rampant increase in obesity that is often accompanied by diabetes.

Physicians divide diabetes into three categories type 1, type 2, and gestational diabetes. Gestational diabetes is relatively rare and is associated with pregnancy. Type 1 represents less than 5% of all cases while type 2 represents about 95% of diabetes diagnoses.

What Is Type 2 Diabetes?

Type 2 diabetes is a serious health condition in which blood sugar levels rise much higher than normal. The CDC reports that one in eight American adults has diabetes. Type 2 diabetes is often preceded by a condition called prediabetes in which blood-sugar levels are higher than normal, but it’s not high enough to be considered type 2 diabetes. Researchers have documented that prediabetes also shortens lifespans. Prediabetes comes with many of the same health-robbing effects as type 2 diabetes, albeit to a lesser extent.

What Causes Type 2 Diabetes?

The fundamental biological changes underlying type 2 diabetes are lack of sufficient insulin production due to metabolic changes of aging and insulin resistance.

Insulin – the hormone the keeps blood sugar levels down – is at the core of the problem. Two problems happen in type 2 diabetics. First, the body does not make enough insulin. Secondly, the insulin that is made cannot effectively lower blood sugar, a condition known as insulin resistance. Insulin resistance is a consistent factor in type 2 and refers to the body’s inability to use insulin efficiently. As a diabetic’s blood sugar levels go up, the pancreas makes extra insulin at first, but eventually, it can’t keep up, causing blood sugar levels to soar. Excess blood sugar wreaks havoc throughout the body, causing damage to a variety of organs and systems.

Mainstay Type 2 Diabetes Treatments

Type 2 diabetes drugs are mostly designed to reduce blood sugar levels. The generic drug metformin is the first-line treatment for type 2 diabetes. In addition to being a diabetes drug, research has shown that metformin users have reduced rates of cancer. Moreover, some researchers are currently testing metformin as an anti-aging drug, because the Bannister study showed that metformin users lived longer than diabetics taking other drugs.

However, if metformin fails, sitagliptin also increases insulin production by inhibiting the dipeptidyl peptidase 4 (DPP-4) enzyme. Sitagliptin goes by the trade name Januvia and was approved by the FDA) in 2006.  Studies show that metformin by itself is slightly more effective than sitagliptin alone, however, the combination of both drugs is highly effective. In 2007, the FDA approved an oral combination of metformin and sitagliptin, which is marketed in the US under the tradename Janumet.

New Type 2 Diabetes Treatments

Newer type 2 diabetes treatments include drugs called incretin mimetics. Three have been approved for use in the U.S., including exenatide (brand name Byetta), liraglutide (Victoza), and extended-release exenatide (Bydureon).  The main disadvantage of these drugs is they must be administered by subcutaneous injection. Incretins are a group of metabolic hormones naturally found in the body that stimulate a decrease in blood sugar levels. The body releases incretins after eating, and the hormones augment the secretion of insulin released from pancreatic beta cells. They also slow the rate of absorption of nutrients into the bloodstream by reducing gastric emptying and may directly reduce food intake.

In 2013, pharmaceutical firms introduced a new class of diabetes treatments called gliflozins that reduce blood glucose levels. These drugs go by the brand names of Farxiga, Invokana, and Jardiance. Ertugliflozin (brand name Steglatro) is the most recent addition to the family of gliflozins and was approved in the United States on December 19, 2017. Gliflozins inhibit reabsorption of glucose in the kidney and therefore lower blood sugar. They are also called SGLT2 inhibitors because they act by inhibiting sodium-glucose transport protein 2 (SGLT2). As studied on canagliflozin, a member of this class, gliflozins enhance blood sugar control as well as reduce body weight and systolic and diastolic blood pressure.

Studies have shown that SGLT2 inhibitors reduce the risk of death by as much as a third in diabetics. Moreover, SGLT2 inhibitors are associated with reduced cardiac disease, weight loss, and reduced hypoglycemia, except when taken with insulin. Unfortunately, gliflozins carry the double the risk of too much acid in the blood, a condition called ketoacidosis, and the FDA has recently highlighted this potentially adverse effect.

UCSD's LMPTP inhibitor is a promising type 2 diabetes treatment.
UCSD’s LMPTP inhibitor is a promising type 2 diabetes treatment. Credit: Darryl Leja, NHGRI.

Type 2 Diabetes Treatments in the Pipeline

The future looks bright as researchers at the University of California in San Diego (UCSD) have shown that a drug reverses diabetes symptoms in mice, by attacking insulin resistance, the root cause of type 2 diabetes.

The team led by Stephanie Stanford at UCSD found that giving diabetic mice a once-daily oral drug that affects insulin signaling restored their ability to control their blood sugar levels. The rodents had developed the condition after a high-fat diet had made them obese. According to the researchers involved with the project, the drug did not seem to produce any side effects in the mice.

The novel therapy inhibits LMPTP, an acronym for ‘low molecular weight protein tyrosine phosphatase.’ LMPTP is an enzyme that is encoded by the ACP1 gene in humans. LMPTP promotes insulin resistance, and the UCSD researchers are testing out the theory that inhibiting the enzyme could be a way of treating type 2 diabetes. By blocking LMPTP, the compound reawakens insulin receptors on the surface of cells – especially in the liver – which normally absorb excess sugar from the blood when they detect insulin.

So far, the compound has only been tested in mice, and the UCSD team needs to perform more research before they know if the treatment will work on people with type 2 diabetes. The UCSD team is beginning safety testing in animals.

Weight Loss Treatments

Weight loss is one of the most effective ways to treat type diabetes, and some patients have had to resort to the drastic measure of gastric surgery, although nonsurgical options are also available.

Researchers have shown that gastric band surgery is an effective diabetes treatment, and can reverse the disease in many cases.

The Elipse gastric balloon manufactured by Allurion Technologies is a nonsurgical solution which accomplishes the same effect. With the Elipse Device, no surgery, endoscopy, or anesthesia is required.

Scientists are working on ways to cure Type 1 diabetes.
Scientists are working on Type 1 diabetes treatments. Credit: Getty Images.

Type 1 Diabetes Treatments

While the bulk of research and promising innovations are for type 2 diabetes, the discoveries for the rarer type 1 lag far behind. The encouraging developments in type 1 diabetes treatments include improved insulin delivery devices, stem cell therapies and the novel pancreas in a box.

Type 1 has a genetic cause and results from the pancreas’s inability to produce enough insulin. While the odds of getting type 2 diabetes increase with age, type 1 manifests earlier in life. Type 1 diabetics control their disease with regular injections of insulin. Injecting insulin is inherently dangerous and carries a higher lifetime risk of death.

The problem for most type 1 diabetics is getting the dose right. Too much insulin can be deadly and too little isn’t too healthy either. Pharmaceutical firms are working on smart insulin devices which automatically increase insulin supply when the blood sugar level is too high, and switch it off when levels are normal. If either firm develops a successful product, it would significantly reduce the risk of hypoglycemia, a severe risk for insulin-injecting diabetics.

Doctors have attempted pancreas transplants on a small number of patients, but this is an impractical and prohibitively expensive solution. The promising developments include using stem cell therapies to grow new pancreatic beta cells and providing a lab-grown substitute called the pancreas in a box.

Diabetes is a Disease of Aging

Type 2 diabetes and prediabetes are chronic diseases of aging and the odds of getting the condition grow with each passing year. These two diseases are rapidly increasing problems among America’s Seniors. According to the CDC, 26% of Americans 65 and older currently have diabetes, and an additional 51% have prediabetes. Taken together, 77% of Americans over 65 have one of the two conditions.

The numbers of people over 65 with diabetes are predicted to almost double. Using information from the CDC, the Institute for Alternative Futures diabetes model estimated that the number of American Seniors living with diabetes would increase to 41% by 2025.

Health Risks of Type 2 Diabetes

Left untreated, the soaring blood sugar caused by diabetes creates serious health problems throughout the body, including blindness, kidney failure, cancer, stroke, heart disease, loss of limbs and double the risk of death.

There is some evidence that high blood sugar itself can contribute to aging. Researchers have linked high blood sugar with high levels of advanced glycation end-products (AGEs). AGEs are thought to contribute to diabetes complications, including cardiovascular disease, eye disease, nerve disease, and kidney disease. Diabetes complications can also speed up the aging process.

Reducing Complications of Type 2 Diabetes

A recent Lancet study found that diabetics are living longer than a quarter of a century ago, due to better drugs for both the disease and its complications. For example, let’s take an average adult diagnosed with type 2 diabetes for the first time at age 40.

According to the Lancet study, the average male diagnosed at age 40 in the 1990’s was expected to lose eight years of life. With the advent of better diabetes treatments in the 2000’s the situation had improved for that same man who was expected to lose about six years.

Women have also seen an improvement in life expectancies. In the 1990’s, a 40-year-old woman was expected to lose nine years of life expectancy. However, with new diabetes treatments a decade later in the 2000s, she was expected to lose just under seven years.

Preventing Type 2 Diabetes

There are many promising new treatments coming into the market for type 2 diabetics. However, the best strategy is to delay or prevent type diabetes.  Moreover, studies show that people with type 2 diabetes can avoid some its deadlier effects with early action. People with prediabetes are high risk for the diseases, and scientists have developed a lifestyle change program that has been shown to significantly reduce the odds of conversion into full-blown diabetes. For prediabetics that are unable or unwilling to make lifestyle changes, the drug metformin has also shown to be effective at reducing diabetes, although to a lesser extent.  Said in another way, prediabetics can avoid becoming full-blown diabetics with the medication metformin, although weight loss through exercise and proper diet are far more effective.

Additionally, a diet rich in fruit in vegetables can help people to lose weight and reduce blood sugar. Studies show that people who eat ten servings of fruits and vegetables every day stay healthier and live longer. In fact, the DASH diet – the US News & World Report’s 2017 top choice for diabetes – is rich in plant foods.

Bottom Line

Reducing the health risks of type 2 diabetes involves many components. Losing weight is one of the best ways to quash diabetes. Moreover, a prevention strategy that tests for prediabetes and then aggressively works to prevent full-blown diabetes also shows impressive results. Furthermore, early detection and treatment of type 2 diabetes can save many more lives. Even for those diagnosed with the disease, medical science has drummed up effective type 2 diabetes treatments and lifestyle changes which can significantly reduce the health-robbing effects of this condition.

Those with type 1 diabetes also have an improved outlook, as science is working on promising treatments that better manage their disease.

Show Us Some Love

  • Share this post on social media and help us spread the word–  It only takes one click on any of the social media links on this page.
  • Follow us on social media –  Google+ | Facebook | Reddit
  • Sign up for our email list – We use your email to notify you of new articles. We will not send you spam, and we will not share your email address. You can cancel at any time.
  • Tell us what you think  – Scroll down to enter your comments below.

References

Cover photo: Dissoid/Getty Images.

Chukwuemeka Nwaneri, Helen Cooper, David Bowen-Jones. Mortality in Type 2 Diabetes Mellitus: magnitude of the evidence from a Systematic Review and Meta-analysis. British Journal of Diabetes & Vascular Disease. 15 July 2013. DOI: 10.1177/1474651413495703. Link to article.

Barone BB, Yeh H, Snyder CF, Peairs KS, Stein KB, Derr RL, Wolff AC, Brancati FL. “Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus A Systematic Review and Meta-analysis.” JAMA. 2008;300(23):2754–2764. doi:10.1001/jama.2008.824. Link to article.

Knowler WC, Barrett-Connor E, Fowler SE, et al. “Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.” New England Journal of Medicine, 2002; 346:393–403. Link to article

The National Institute of Diabetes and Digestive and Kidney Diseases. Diabetes Prevention Program (DPP). Online publication.  Link to article.

Ulrike Hostalek, Mike Gwilt, Steven Hildemann. Therapeutic Use of Metformin in Prediabetes and Diabetes Prevention. Drugs. 2015; 75(10): 1071–1094. doi:  10.1007/s40265-015-0416-8. Link to article.

Stanford, Stephanie M et al. “Diabetes Reversal by Inhibition of the Low Molecular Weight Tyrosine Phosphatase.” Nature chemical biology 13.6 (2017): 624–632. PMC. Web. 22 Dec. 2017. Link.

Alan Morris. “Diabetes: LMPTP inhibitors — potential treatment for type 2 diabetes?” Nature Reviews Endocrinology 13, 316 (2017) DOI:10.1038/nrendo.2017.46. Link.

Disclaimer

Diagnosis, Treatment, and Advice:  This article is intended for educational and informational purposes only and is not a substitute for qualified, professional medical advice.  The information and opinions provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. Consult a qualified and licensed physician for the diagnosis and treatment of any and all medical conditions. Experimental diabetes treatments carry a much higher risk than FDA-approved ones. Call 911, or an equivalent emergency hotline number, for all medical emergencies. As well, consult a licensed, qualified physician before changing your diet, supplement or exercise programs.  Photos, Endorsements, & External Links:  This article is not intended to endorse organizations, companies, or their products. Links to external websites, mention or depiction of company names or brands, are intended for illustration only and do not constitute endorsements.

8 Replies to “Scientists Hunting for Breakthrough Diabetes Treatments”

  1. Alan Green M.D.

    Anyone trying to understand diabetes should start with paper, “TOR-centric view on insulin resistance and diabetic complications: perspective for endocrinologists and gerontologists, Blagosklonny, 2013.
    People with type 2 diabetes die from complications of elevated mTOR. Elevated mTOR is main cause of vascular disease, coronary artery disease, kidney failure, retinopathy causing blindness, neuropathy, leg amputations. High glucose and high insulin both cause elevated mTOR. At time of diagnosis of diabetes, when first have elevated glucose, 25% already have cardiovascular disease, 8% have retinopathy, 10-18% have neuropthy.
    Pre-diabetic need to lower insulin resistance which causes high insulin levels. High insulin levels cause damage to beta cells (indirectly) and high insulin causes high mTOR.
    Biggest factor is overweight and obesity. Exercise important; but overweight much more important.
    People should be focused on prevention, not getting diabetes instead of being treated.

    • Brady Hartman

      Dr. Green – I haven’t read that paper – thanks for pointing that out — as I wasn’t aware of the mTOR angle. Diabetes and dysglycemia are so common, and largely preventable, as you said by reducing overweight.

Comment? Tell us what you think using your Twitter, Facebook, or Google+ account.