Research was published in the Journal of the American College of Cardiology today with analysis of three different clinical trials that looked at Lipitor (scientific name: atorvastatin). The authors found new evidence that taking Lipitor slightly increased your chance of eventually getting diabetes. There have been several studies before this, and this research increases the evidence of this effect.
“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.”
In the study where Lipitor seemed to increase the risk of diabetes the most, 8.7% of people who received the drug eventually got diabetes whereas only 6.1% of people who received the placebo got the drug. This means that Liptor recipients were 37% more likely to get diabetes.
That said, the overwhelming majority (over 90%) of individuals in all the trials did NOT get diabetes. This research suggests that people on Lipitor should be closely monitored for the development of diabetes – but not that they should discontinue taking it. Lipitor has been shown to help decrease the risk of having a stroke or heart attack – as well as some other forms of heart disease.
The big news in the diabetes world this week is a new article in the New England Journal of Medicine (link here) about how Actos (scientific name: pioglitazone) can help prevent the development of diabetes in folks with prediabetes. The American Diabetes Association has a handy page for helping determine if you have “prediabetes” (link here). If you’re looking at HbA1c, it means that you are between 5.7% and 6.4%.
Dr. Ralph DeFronzo at the University of Texas Health Center – San Antonio was the lead author and researcher on the study. During the clinical trial, they enrolled over 600 individuals who had been diagnosed with prediabetes and assigned them to receive either a placebo or Actos. Following them over the course of several years, 7.6% of individuals on placebo developed to full blown diabetes each year, whereas only 2.1% of individuals on Actos developed the disease. (You should note that this means over 90% of both groups did NOT progress to diabetes each year.)
This sounds very promising – but more work definitely needs to be done prior to prescribing the drug to the 79 million people in the United States who have prediabetes. Matthew Harper at Forbes points out some of the problems:
“But patients on Actos were significantly more likely to have side effects, including fluid buildup and weight gain. There were a few more heart problems, and three deaths in the Actos group compared to one in the placebo group. That doesn’t mean Actos was costing lives, but it was not saving them.”
He also points out that similar results had previously been seen in Avandia. At this point, Avandia’s use in diabetes patients has been severely restricted because of the cardiovascular problems it can cause. Additionally, previously research has shown that lifestyle changes can reduce the incidence of diabetes fairly effectively as well.
Takeda, the manufacturer of Actos, was one of the sponsors of this study. No drug has been approved by the FDA previously for the prevention of diabetes – it will be interesting to see what research is done next and whether or not Takeda pursues such an indication.
Merck is running an incredibly large, international clinical trial examining the long-term effects of using Januvia (scientific name: sitagliptin). (Trial on Corengi site here.)
Patients with type 2 diabetes are enrolled, kept on their current regimen of medications and assigned to receive either Januvia or a placebo. This is a double-blind trial, meaning that neither the patient nor the physician will know whether or not he or she got Januvia or the placebo.
The trial is looking to enroll about 14,000 people – this is a big trial. The trial started in December 2008 and originally didn’t accept patients who were on insulin. They just changed the criteria so that even folks who are on insulin can enroll. Now, in order to qualify, you need:
Have HbA1c between 6.5% and 8.0%
Be on stable mix of diabetes drugs (which may include insulin)
Have cardiovascular disease of some type
I talked to one of the folks involved in the trial at one of the study locations at Washington State University and asked them about the change (allowing folks on insulin to participate). Debbie Weeks, a nurse and research associate there, suggested they changed because diabetes is being treated very aggressively in some areas – and they need to allow patients on insulin to participate.
Interested in finding out more? There’s probably a location nearby (click on the map below and go to the contacts/locations tab). The toll-free number at Merck to get connect with a location near you is 1-888-577-8839
Researchers just published a new analysis of previously published results of 16 studies that involved more than 800,000 patients who had taken either Avandia or Actos. They found that, compared to Actos, Avandia was more likely to cause either heart attacks or congestive heart failure.
“In the new analysis, researchers looked at the results of 16 studies that involved 810,000 users of Avandia or Actos (pioglitazone), a similar diabetes medication. The findings appear online March 17 in the BMJ.
The researchers found a “modest but statistically significant increase” in the odds of certain heart conditions in those who took Avandia. The risk of heart attack rose by 16 percent and increased 23 percent for congestive heart failure. Overall, mortality rates rose 14 percent.”
The research was published in the British Medical Journal. Interestingly, there’s an accompanying editorial by Dr. Victor Montori and Dr. Nilay Shaw at the Mayo Clinic that is incredibly critical of how this story has played out (link here). The last paragraph of their editorial is below (by the way, rosiglitazone is the scientific name for Avandia).
The rosiglitazone story says much about how healthcare has become less about promoting patients’ interests, alleviating illness, promoting function and independence, and curing disease, and much more about promoting other interests, including those of the drug industry. Has the corruption of healthcare advanced so far that it is unreasonable, even naive, to expect responsible drug companies, enlightened regulators, and thoughtful prescribers?
The Journal of Diabetes Science and Technology just published research about the initial development of a disposable glucose sensor that uses your tears to determine your glucose level. Scientists from Arizona State University as well as the Mayo Clinic developed a prototype for a device that would be less painful than a finger prick. From the published article (link here):
“An integrated device concept for sampling and sensing of tear glucose, featuring screen-printed electrical leads (A), an insulating layer (B), a silicone fluidics piece (C), a sensing well covering the three electrode system (D), and an absorbent sampling material (E).”
Using funding from BioAccel, the team is now compiling data to apply for human clinical trials of the device, but major challenges remain, including accuracy, efficiency, speed of performing the test, reproducible results, and of course making sure the test sample does not evaporate before it can be read.
Recent research has confirmed the conventional wisdom that metformin is the best choice for initial treatment when diagnosed with type 2 diabetes. Researchers examined over 160 previously published studies that looked at a variety of several different classes of drugs and came to the conclusion that metformin as a single therapy worked better than all the others. The study, soon to be published in The Annals of Internal Medicine, looked at both the benefits of the medications as well as their side effects.
From the new article on Endocrine Today (link here):
Results indicated that most medications used as monotherapy yielded comparable decreases in HbA1c (about one absolute percentage point on average throughout the course of a study). Metformin alone, however, lowered HbA1c more than DPP-4 inhibitors alone, and any type of combination therapy reduced HbA1c by about one absolute percentage point more than monotherapy.
They also wrote:
“Although the long-term benefits and harms of diabetes medications remain unclear, the evidence supports use of metformin as a first-line treatment agent,” the researchers wrote.
Disappointing news from GSK and Tolerx today as they announced that their Defend-1 clinical trial didn’t meet its goals.
These companies were looking to see if a protein called otelixizumabcould help individuals who had just been diagnosed with type 1 diabetes. In this clinical trial, called Defend-1, adult patients diagnosed with type 1 diabetes were given an 8-day course of the protein shortly after diagnosis. Twelve months later, these patients were analyzed to see if the treatment had helped increase something called c-peptide, which is an indicator of insulin production. Unfortunately, they didn’t find that the treatment increased the level of c-peptide at all.
There’s a followup to this trial (cleverly called Defend-2) that has been suspended while further analysis of the data is going on. (More information at the xconomy website here.)
Lantus (scientific name: insulin glargine) is a long-lasting insulin that individuals take once a day. Used for some diabetics taking insulin (but not all), daily insulin can be an important part of keeping your HbA1c in check. (Lantus is manufactured and sold by Sanofi Aventis.)
A different pharmaceutical company, Novo Nordisk, recently studied a 3-times-per-week shot of insulin – called “Insulin Degludec” – and compared it to Lantus. (Full story in Times of India here.) This clinical trial, conducted at 28 sites in the United States, Canada, India, and South Africa over 16 weeks, found that Insulin Degludec was just as effective at controlling HbA1c as Lantus. (Note: it wasn’t more effective – it was just as effective). Still, this might be an important option if approved for those people who don’t like to take daily shots. (Now that I think of it, that might be most people.) From the article:
Dr Anoop Misra, chairman of Fortis Hospital’s centre of excellence for diabetes, said, “This is quite a breakthrough. For the first time, we have a ultra-long acting insulin with stable action. This will lead to lesser injections (once in two days) for the patients with good blood sugar control.”
This was a phase 2 trial (I’m pretty sure it was this one) – with a little over 100 participants. In order for Novo Nordisk to get this approved, they’ll have to conduct a phase 3 trial over a longer time period with more participants. It doesn’t look like they’ve launched any such trial yet – but when they do, it will be listed on the Corengi website (as well as clinicaltrials.gov).