This news release from Newcastle University reports on a small pilot study testing whether type 1 diabetes patients who add the drug metformin to their daily regimen reduce their risk of cardiovascular disease. Based on a reduction in markers indicating blood vessel damage, and an increase in markers indicating blood vessel repair, the researchers conclude the risk is lowered, but the study wasn’t designed in a way that would show an actual risk reduction. Thus, claims such as this one by the study researchers — “this study has shown metformin has additional benefit beyond improving diabetes control when given to patients with relatively well controlled Type 1 diabetes” — represent an overreach, because the study wasn’t capable of showing a benefit on any outcome that would actually matter to a patient. Additionally, the release offers no numerical data on changes in levels of the measured markers — only general statements. Nor does it mention the cost of the drug, which is nominal, but which could garner a large sales market. Lastly, it offers a patient testimonial by way of anecdotal information which may or may not be representative of the experiences of others.
Type I diabetes is a serious lifelong disease that places patients in a constant state of risk, depending on their blood sugar levels. People with the disease are more prone to cardiovascular disease so any treatment that might lower that risk, slowing that degradation, should benefit the 400,000 people in the United Kingdom who have this disease, as well as similar patient populations around the world. Because of that, people deserve quantitative information about how treatments affect patient outcomes improvements in treating the disease, and this release, sadly, offers little. Because the study reports on disease oriented outcome but doesn’t measure any patient oriented outcomes, it should be followed by a large randomized clinical trial conducted over a very long period of time.
The release makes no mention of costs at all, although the unit cost of the drug is both quite low and readily available. Diabetic patients already spend a substantive amount for their medications over their lives and knowing that the addition of this other drug would not be an undue financial burden would be a welcome piece of information. Since the study was done in the UK, one might have expected some comment on the effect of the use of this drug in a large number of type I diabetics on the health care system.
The release makes clear that cardiovascular disease is a major risk for patients with diabetes and the study was intended to show whether the additional drug, metformin, could lower that risk. The release states that the study showed a decrease in markers indicating damaged blood vessels and an increase in markers showing blood vessel repair, among other findings. But the release falls short by not providing any numerical data suggesting the degree of improvement in these markers, and therefore denies readers the ability to make their own determination as to the importance of this research.
The release makes no mention of any side effects or harms to participants from the use of metformin, although a host of minor-to-moderate side effects may be routinely seen with this drug. The research paper itself limits discussion of side effects to “any major or severe episodes of hypoglycemia,” which it defines as instances of low blood sugar “requiring intervention of another person to resolve the event,” or any episode of hypoglycemia “resulting in a loss of consciousness.” Although none were reported, both instances seem substantively more serious than minor side effects. Gastrointestinal side effects, for example, are commonly reported by patients taking metformin. And there are some relatively commonly found metabolic adverse effects of metformin (metabolic acidosis) that could have been looked for to determine if there is an increased incidence in this ‘vulnerable’ group.
While the research paper goes into substantial detail in providing numerical data on the levels of markers measured in this study, the news release offers none of that. It does state that this was a pilot study comparing a small number of patients split between the standard treatment for type 1 diabetes and those receiving additional doses of metformin. It also states that findings from these patients were compared to those from a group of healthy volunteers. But again, the findings reported in the release are general statements that offer readers no way to gauge change.
Perhaps more importantly, the release never directly cautions that the outcomes studied are surrogate markers of risk, and that the study wasn’t capable of showing an actual reduction in the number of cardiovascular events — something which may or may not be demonstrated in additional studies.
Lastly, there is a feature of the study that raised some questions. There was a “run-in” period (often used by drug sponsors to select or exclude patients based on their potential response to the drug) that was not clearly or comprehensively described. There is no description of what was measured here and what the criteria were for “passing” the run-in period.
The release does not appear to commit disease mongering.
The release mentions that the study was funded by the Diabetes Research and Wellness Foundation and the Diabetes Research Fund in Gateshead. Neither the news release or published study address potential conflicts of interest. The funding foundation lists only its board of directors and no background information on the group is readily available.
There are no mentions in the release of possible alternatives to metformin as a means to reduce the risk of cardiovascular disease in type 1 diabetes patients. It would be of interest to patients to know if intensive dietary and exercise counseling had been studied and what the results were.
Since metformin is readily available and currently used in treating type 2 diabetes, the release gets a satisfactory rating in this category.
Since cardiovascular disease is a major risk for diabetic patients, research indicating that an existing (presumably inexpensive) drug may lower that risk clearly qualifies as significant enough to warrant a release, in spite of the fact that this was only a small, limited pilot study.
This release does not appear to offer any unjustifiable language per se. However, the release seems to point only towards this being totally beneficial without any statement about the likelihood that this “basic science” study would translate to clinically important patient centered outcomes.
And there are statements that are clearly overreaching. For example, “We have established the drug increases patients own vascular stem cells, which will help delay or slowdown heart disease.” It’s not at all clear that increasing vascular stem cells will delay or slow down heart disease. We’d need another much larger larger study to show that.
Finally, use of anecdotal statements from a trial participant offers little of value for readers. We don’t know if his was the best experience among all the participants, or the worst, or somewhere in between.