Lipitor increases the risk of Type 2 Diabetes?

A study appearing in the Journal of the American College of Cardiology suggests that high doses of Lipitor may be linked to an increased risk in developing Type 2 Diabetes:

We used a standard definition of diabetes and excluded patients with prevalent diabetes at baseline. We identified baseline predictors of new-onset T2DM and compared the event rates in patients with and without new-onset T2DM.

High-dose atorvastatin treatment compared with placebo in the SPARCL trial is associated with a slightly increased risk of new-onset T2DM. Baseline fasting glucose level and features of the metabolic syndrome are predictive of new-onset T2DM across the 3 trials.

Of course, this is not the first study that has suggested this type of connection.  However, consider …

But it also suggests that the risk may largely exist among people who also have the well-known risk factors for type 2 diabetes — including excess weight, high blood sugar, elevated triglycerides (a type of blood fat) and high blood pressure.

Those four factors appear “very good at distinguishing people at high or low risk for developing new-onset diabetes with atorvastatin,” lead researcher Dr. David D. Waters, of the University of California at San Francisco, told Reuters Health in an email.

So managing those risk factors — by shedding excess pounds, for example — would be important for curbing any extra diabetes risk, Waters said.

He also stressed that the diabetes risk tied to statins is small.

“An important point,” Waters said, “is that the risk of developing new-onset diabetes and its complications (is) greatly outweighed by the benefit of statins in reducing cardiac death, heart attack and stroke.”

In other words, Waters claims that the risk of diabetes is less than the risk of cardiac or stroke events if Lipitor is not used.



Victoza Approved for Diabetes Treatment in China

Novo Nordisk announced today that the Chinese State Food and Drug Administration (SFDA) has approved Victoza® for the treatment of type 2 diabetes.

With Western foods and higher incomes, Type 2 Diabetes is a growing problem in the most populated country on the planet.

Victoza, a brandname for liraglutide, is a once-daily human Glucagon-like peptide analogue and is used as an add-on to metformin.


Metformin Remains Number One Type Two Drug

As one of the most widely prescribed diabetes drugs, the preferential application of metformin to treat Type 2 was confirmed by a new study.

The study examined and compared six different types or classes of medications for treatment of Type 2 Diabetes:  DPP-4 inhibitors (Onglyza, Januvia), sulfonylureas (Amaryl, Glucotrol and others), thiazolidinediones (Avandia, Actos), meglitinides (Prandin,Starlix), GLP-1 receptor agonists (Byetta and Victoza),  and metformin (Fortamet, Glucophage,Glumetza, and Riomet).

Metformin was found to be efficacious (reduced hemoglobin A1c), had the fewest side effects and was the cheapest.

Ultra Long Acting Insulin – Degludec – Three Times per Week

We’ve been hearing about Novo Nordisk’s Ultra Long Acting Insulin, Degludec, as a result of the series of preliminary studies that were published last year.

Now a more comprehensive investigation, conduced in India, Canada, US and South Africa, has been completed which compared the insulin to Glargine (or Lantus).  A significant difference between the treatment protocol was the frequency of injection with Glargine requiring a daily administration while Degludec was taken every 48 hours.  However, the total daily dose (TDD) administered was the same for each.

Investigators found Degludec to be equialent to Glargine in terms of effectiveness (similar reductions in HbA1c).  The duration of apparently consistent insulin action is intriguing and I’d like to see a plot comparing the pharmacokinetics of the two insulins.

At last year’s European Association for the Study of Diabetes (EASD) annual meeting, the following was presented:

Despite the poor scaling and 24 rather than 48-hour x-axis, the concentration-time profile is flat.

Novo Nordisk spokesperson reportedly told WebMD that the company plans to seek approval later this year to market the long-acting insulin in both the U.S. and Europe.

So here’s the question…. not knowing the cost of Degludec, let’s just assume it’s more expensive.  If you had to pay more for Degludec but were able to inject every other day would you?

New drug uses SGLT2 inhibition – excess glucose kidney excretion – to lower glucose

This is interesting, perhaps even exciting because it represents an innovative way to manage diabetes independent of insulin (press release emailed to me this AM):

Bristol-Myers today announced that the U.S. Food and Drug Administration (FDA) has accepted for review a New Drug Application (NDA) for dapagliflozin, an investigational compound for the treatment of adults with type 2 diabetes mellitus. A Marketing Authorisation Application (MAA) for dapagliflozin has also been validated by the European Medicines Agency (EMA). The NDA and MAA submissions for dapagliflozin were filed in December 2010. The Prescription Drug User Fee Act (PDUFA) goal
date for the FDA is October 28, 2011.

The U.S. and European submissions included data of up to two years in duration from a global development program involving approximately 6,000 individuals in 40 clinical studies. In accordance with FDA guidelines, the U.S. application also includes data assessing the cardiovascular safety of dapagliflozin in adults with type 2 diabetes.

If approved, dapagliflozin would potentially be the first in a class of novel agents for diabetes that inhibit sodium-glucose cotransporter-2 (SGLT2), a specific target located in the kidney. Through this mechanism, dapagliflozin is designed to help control glycemia independently of insulin pathways, leading to the excretion of excess glucose and associated calories in the urine.

How does it work?

The renal SGLT system plays a major role in overall glucose balance in the body. Normally, the kidney filters ~180g of glucose each day, and virtually all is reabsorbed back into circulation. Glucose reabsorption occurs in the proximal tubule of the kidney via the SGLT system. Selective inhibition of SGLT2 by an insulin independent mechanism of action is designed to lead to the excretion of excess glucose and associated calories in the urine, thereby lowering blood glucose levels.

I’ll research and update later.  Comments?

Good Side Affects?

Usually drugs for disease treatment are listed with serious side affects. However, researchers have noted that certain certain drugs for type II diabetes also appear to lower patients’ blood pressure. Drugs called thiazolidinediones (TDZs), which are used to treat type 2 diabetes appear to lower blood pressure. Since most individuals with Type 2 diabetes are at risk for serious cardiovascular problems, including atherosclerosis, heart attack, stroke and hypertension.

Cardiac Drug may Provide Treatment for Diabetes

Reuters is reporting breaking news about a drug that dramatically reduces the risk of developing diabetes from the American College of Cardiology scientific meeting in New Orleans
Although AtheroGenics Inc.’s experimental heart drug actually missed its primary goal during a the 6,144-patient trial, it did dramatically reduce the risk patients would develop diabetes. In addition, the drug improved glycemic control among those with diabetes:

Patients in ARISE taking AGI-1067 were 64 percent less likely to develop new onset diabetes (p < 0.0001). In patients with diabetes, AGI-1067 improved glycemic control as measured by reductions in HbA1c of 0.5 percent at 12 months (p < 0.0001). These patients had a mean baseline HbA1c of 7.2 percent.

The reduced risk of developing diabetes is significant but as I look at these results, the HbA1c levels seem somewhat low – my understanding is that the “average” diabetic has levels between 9 and 10 percent. In fact, at 7.2%, the patient population had a close to ideal glycemic control. I’m wondering if the secondary outcome is somewhat biased by an exclusion criteria which led to a population of diabetic subjects with lower than average levels.
To put the result in perspective, studies have shown that there is a 10% decrease in relative risk for every 1 % eduction in A1c. So, the 0.5% drop in HbA1c could be used to suggest a potential 5% drop in the risk of developing complications. This seems quite modest.
The medication itself is an anti-oxidant, anti-inflammatory drug, the first of its kind. Obviously, having missed the primary goal, further research will be necessary to confirm application in other areas.
“In diabetes there was a profound effect, and that needs to be followed,” said Dr. Marc Pfeffer, a co-principal investigator of the study. “I’m pretty bullish that we need to go to the next step.”

Appetite-Fighting Molecule May Fight Obesity

Obesity is global epidemic in both developing as well as developed nations, and according to the World Health Organization, of the estimated 1 billion adults worldwide who are overweight, about 300 million are considered obese. Obesity is a major risk factor for type 2 diabetes, cardiovascular disease, hypertension and stroke, and some forms of cancer. Now, Japanese researchers are hopeful that they have found a class of molecules, such as nesfatin-1, that will offer future promise in treating obesity.

Study Says Tequin Could Produce Diabetes

prod_shot.gif A Canadian study urges doctors to stop prescribing the Bristol Myers Squibb antibiotic, Tequin (gatifloxacin), saying it can have “life threatening” side effects, including diabetes.
Elderly people who took the medication were 17 times more likely to develop serious diabetes than if they took a different antibiotic, and were four times more likely to be hospitalized for low blood sugar.
The study was slated for a March 30 publication date in The New England Journal of Medicine, but was released earlier due to the importance of its findings.
A research Study using rats indicates that Gatifloxacin-induced secretion of insulin and epinephrine would contribute to the abnormalities in glucose homeostasis (see link below).
Related: Effects of gatifloxacin on serum glucose concentration in normal and diabetic rats.

Diabetes Patients Report Drug Side Effects

Avandia and Avandamet reportedly have caused blurry vision and swelling of the legs and feet of some patients. The information comes from the Food and Drug Administration and manufacturer GlaxoSmithKline.
The majority of those patients also reported peripheral edema, or swelling of the legs, ankles and feet, the company said in a letter sent last month to doctors. In some cases, stopping treatment or reducing the dose eliminated or improved the condition, it added.
Avandia, in addition to diet and exercise, improves blood sugar control in adults with type 2 (non-insulin-dependent) diabetes. The drug can be used alone or in combination with a sulfonylurea, metformin, or insulin when diet, exercise, and one of these agents or diet, exercise, plus Avandia alone are not enough to control blood sugar.
more from the FDA here.

New Diabetes Pill Deemed Dangerous

A new diabetes pill that was headed for government approval has been linked to deaths, heart attacks and strokes, a medical journal reported Thursday in an analysis it said was rushed online to head off a Vioxx-like fiasco
The study by leading heart researchers found twice as many deaths and cardiovascular problems in diabetic adults taking the drug Pargluva as those on dummy pills or a competing drug.

[Read more...]

US Panel Recommends Exubera inhaled insulin

Good news for insulin users: an advisory panel voted 7-2 to urge the Food and Drug Administration to approve an inhaled insulin (Exubera).

[Read more...]

Biovail, Depomed Announce Regulatory Approval of Glumetza to Treat Type II Diabetes in Canada

More options are available for individuals with Type II diabetes as Biovail Corp.’s diabetes drug Glumetza received approval in Canada. Approval has been granted for two dosage strengths of the drug, a formulation of metformin hydrochloride, and are taken once-daily.

Glumetza offers a significant advantage to both physicians and patients by simplifying the dosage regimen of twice-a-day or three-times-a-day metformin to once a day,” the firm said.
more from the National Post.

[Read more...]

Reports of Blindness Surface Related to use of Viagra

The U.S. Food and Drug Administration said it has received about 38 reports of the rare condition among users of Viagra, four reports of blindness among users of Eli Lilly and Co.’s Cialis and one report of the condition in men talking Levitra, made by GlaxoSmithKline Plc.
Pfizer said outside of clinical trials, Viagra has been used by more than 23 million men worldwide over the past seven years. It said reports are extremely rare of visual loss due to the condition known as non-arteritic anterior ischemic optic neuropathy (NAION).
“FDA is aware of these reports but has not determined there is a cause and effect due to use of Viagra … We’re working with the company to make sure this information is available to doctors and patients,” FDA spokeswoman Susan Cruzan told Reuters.

Byetta (exenatide) Continues to Make the News

The latest story is from Reuters:

For people with type 2 diabetes whose blood sugar is inadequately controlled when they’re on two oral anti-diabetes medicines, the addition of an injected drug called exenatide is helpful, researchers report.
Dr. Alain D. Baron told Reuters Health that exenatide is the first in a new class of diabetes drugs and “is now approved for marketing under the name Byetta.”

See my prior post for more information: FDA has approved a diabetes drug derived from lizard saliva

Firms Compete for future Inhaled-Insulin Market

With Type 2 diabetes skyrocketing (thee American Diabetes Association suggests 18.3 million U.S. residents — 6.3% of the population — have the disease) and newly diagnosed adults reluctanct to use insulin injections four times a day, companies are hoping to capitalize on the potential $3 billion inhaled insulin market. As several firms seek FDA approval, analysts wonder if insurance companies reimburse the expensive product.

[Read more...]

FDA has approved a diabetes drug derived from lizard saliva

The FDA has approved a diabetes drug derived from lizard saliva for patients who have not responded to other treatments. Exenatide, developed by Eli Lilly and Co. and Amylin Pharmaceuticals Inc., is an injectable drug to be sold under the brand name Byetta, as an additional therapy for patients with Type II diabetes whose blood sugars are not sufficiently controlled by two oral medications.
Interestingly, exenatide is a synthetic version of saliva of the Gila monster lizard that lives in the Arizona desert and is the first of a new class of drugs known as incretin mimetics. It mimics hormones, released in the human gut in response to food, that help regulate glucose levels.
Analysts expect the drug could eventually generate sales of about $1 billion to $2 billion.
more from Reuters
Speed of Thought has more.

[Read more...]

Inhaled Insulin Said to Be ‘Safe’ and ‘Effective’

Test results presented at the Diabetes UK annual conference in Glasgow showed that for people with Type 2 diabetes already on tablets, inhaled insulin gave better blood glucose control than taking more tablets as treatment.
Among patients with Type 1 diabetes, four years of inhaled insulin treatment combined with a daily long-lasting insulin injection was shown to be effective, with no serious side effects:

Douglas Smallwood, chief executive of Diabetes UK, said: “Since insulin was discovered in the 1920s, injections have been the only option. That can be difficult for some people.
“Many attempts have been made to come up with new treatments and at last we appear to be close to
success,” he said.
“While it will not be suitable for everyone this could make a real difference to the daily lives of many people with diabetes.”
Pfizer and Sanofi-Aventis Group were seeking approval to market Exubera, their inhaled insulin powder, from both the European Medicines Evaluation Agency and the US Food and Drug Administration, Pfizer said.

Source: IOL Medical