I had to
laugh. Of course, by “everyone” the title of this
Medscape
piece meant, I thought, as the “Initial Choice of Oral
Glucose-Lowering Medication” for [treatment of type 2] Diabetes Mellitus.” But
for a moment I thought that the authors meant “everyone everyone.”
That’s the way the
new guidelines for prescribing statins are being interpreted, at least
for everyone over 39 years of age (and under 76),
and that for the very dubious, almost exclusive purpose of lowering
LDL-C. But if you want to read about that, you can go to The Nutrition Debate #
180, “The
AHA/ACC Cholesterol Guidelines.”
No, this
story, published in JAMA
Internal Medicine, was an “observational cohort study [that] sought to
determine the effect of initial oral glucose-lowering class on subsequent need
to additional anti-hyperglycemia therapy.” The 15,516 participants, none of
whom had previously been treated for diabetes, were started on 1) metformin, 2)
a sulfonylurea, like glyburide or glipizide, 3) a TZD like Avandia, or 4) a
DPP4, like Januvia and Onglyza. “The primary outcome was time to treatment
intensification, defined as initiation of a different class of oral
glucose-lowering medication,” Medscape
said.
“Secondary
outcomes included time to composite cardiovascular event (coronary heart
disease, congestive heart failure, unstable angina, ischemic stroke, acute
myocardial infarction [heart attack], or a revascularization procedure),
congestive heart failure alone, an emergency department visit or hospital visit
for hypoglycemia, and any other diabetes related emergency department visit.”
That’s one heck of a scary list of secondary outcomes. Something to think
about…
“The
Winner, and Still Champion: Metformin,” the Medscape
sub-head declared. Well, there should be no surprise there. But if you are now
pre-diabetic, or when first diagnosed a type 2 diabetic, you aren’t (weren’t)
started on Metformin, you might want to print this post out – better yet, go to
the Medscape and JAMA Internal Medicine links above, print them out, and give them to your doctor and ask why you were not. I’d be interested to hear his or her answer.
The
FINDINGS: “58% of the patients began therapy with metformin, 23% with a SU
[sulfonylurea], 6% with a TZD and 13% with a DPP4.” During the “median
follow-up of slightly more than 1 year, subsequent treatment intensification
differed significantly by drug class. Of patients prescribed metformin, 25%
required a second oral agent, compared to 37% of SU recipients, 40% of TZD
recipients, and 36% of patients taking a DPP4.” This implies significantly
different effectiveness.
The
Medscape piece amplifies this finding: “Relative to metformin uses, the risk of
treatment intensification was 68% greater among SU users, 61% greater among TZD
users, and 62% greater among DPP4 users.” That’s really significant.
As to the
“secondary outcomes,” Medscape states this simple but dramatic finding: “Also
relative to metformin, SU use was
associated with an increased risk for composite cardiovascular events,
congestive heart failure, and hypoglycemia.”
Then this
Medscape analysis of comparative effectiveness took an interesting turn. It
began with this question, posed by another
study: “Can People With Type 2 Diabetes Live Longer Than Those
Without? A Comparison of Mortality in People Initiated With Metformin or Sulphonylurea
Monotherapy and Matched Non-diabetic Controls.” This British study, which
appeared in Diabetes Obesity and
Metabolism, essentially asked, “Does Metformin Reduce Mortality?” Hmmm…
Maybe the title of the Medscape piece
was intended to mean “everyone everyone.” I read on to find
out.
In this
study, “patients initiating metformin therapy were compared with those
initiating treatment with a SU, and both diabetic groups were compared with
their matched nondiabetic controls.” Subsequent mortality was tracked for up to
5.5 years. The FINDINGS: “Crude death rates were substantially lower for
metformin users that SU users” and, “All subgroup comparisons favored metformin
over SU and were statistically significant.” But here’s the zinger.
“Perhaps
the most striking finding was that survival time for controls [the
non-diabetics who were not taking
metformin] was 15% shorter than for matched metformin users. This finding was
consistent across all subgroups, nearly all of which demonstrated statistical
significance, and was particularly strong among patients with high
comorbidity.”
“The
protective effect of metformin relative to SUs was not a surprise,” the
Medscape piece says. The remarkable finding was an apparent protective effect
of metformin compared with nondiabetic individuals. Because of metformin’s
favorable results among people with diabetes, it has been postulated that the
drug may also provide benefit to people without diabetes.” Sort of like statin
therapy… What are they saying? What am I saying? Everyone should take
metformin??
The main problem I have seen with Metformin for T2 diabetics is a total lack of education about what it can actually DO. I see people who think it works like insulin - "If I eat 2 cookies, I'll just taken an extra pill today." So they take the medication and still keep on eating high carb crap and...oh my...they just keep getting worse. Guess that calls for more medication, right? I think a better way to go than simply say everyone could benefit from metformin would be to find out why that seems to be, then figure out a way to duplicate the effect without the drug. I found I could no longer take metformin on a strict LCHF diet because the drug exacerbated very bad cramps. Why? Maybe because I wasn't storing glycogen in my liver on that diet, and the metformin compounded the problem? I don't know, and of course the doctor wasn't interested in finding out.
ReplyDeleteI completely agree with your first point. Doctor’s are partly to blame, of course. They think, like Mr. Gruber, that Americans are too stupid to understand the principal mechanism of action of metformin, or at least the one most understood at the moment.
DeleteMy understanding is that the full mechanism and range of action of metformin is not understood. I haven’t studied this recently, but I always say that the main reason I take metformin is to deal with gluconeogenesis from eating too much PROTEIN at dinner. I want to suppress this unwanted glucose production from unused amino acids returned to the liver and stored there for this explicit purpose, as a backup source of glucose production when glycogen stores are low and nearly exhausted. After all, the body does require some glucose for various purposes where cells do not contain ATP.
But patients think, as you say, that if they are being medicated for prediabetes or frank T2DM that that medication will suppress serum glucose from ingested CARBOHYDRATES. It does not.
Of course, metformin apparently has other lesser and lesser known mechanisms of action, but suppression of gluconeogenesis is the one that needs to be told to patients so that they can understand that difference (between PROTEIN and CARBOHYDRATES), but most patients are low-information consumers of health information. They just want their doctors to be in charge of their healthcare. They are essentially in denial, and continue to be so at their own peril. But doctors also have a responsibility, and I’m not sure they are doing their part.
Of course, my blog post was reproting on a epidemiological study that suggested that metformin has a benefit in terms of all cause mortality over a population of non- diabetics not taking it compared to a population that was taking it, which is an interesting finding and suggests yet another mechanism of action that I think does support further research. Of course, I like your idea too that once the mechanism is better understood, we could duplicate it in a way that did not require taking a drug. I am with you on that 100% as well.
This is my first time I visit here. This is really awesome post ! please try to publish some more like this one.
ReplyDeleteThanks
cardiology fellowship
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