I’m a big fan – a devotee you
might say – of Jason Fung, MD, a Canadian nephrologist, blogger, and author.
His very good book, “The Obesity Code” (2016), has been hugely popular in large
part because it is comprehensible to the lay reader. He is also a frequent
blogger, and his 2016 post, “Futility of Blood
Sugar Lowering in T2D,” like a previous one, “Obesity is Protective,”
Retrospective #341, got my attention.
All reasonably well-informed
students of diabetes – including clinicians who treat diabetics,
endocrinologists, diabetologists, as well as Certified Diabetes Educators
(CDEs) and Registered Dieticians (RDs) – are familiar with two large, long-term
UK studies, the DCCT and the UKPDS, and the US follow-up, the ACCORD study.
What Fung did in his recent blog post was succinctly summarize the findings of
those studies and posit, in conclusion, “…that blood glucose lowering in type 2
diabetes is largely useless.” That was a pretty stunning conclusion.
His logic, however, is impeccable.
“The DCCT study…had already established the paradigm of tight blood sugar
control in Type 1, but whether this held true for Type 2 remained to be seen,”
he said. In UKPDS33, he went on, a large cohort of “newly diagnosed T2D
patients who failed a 3 month lifestyle therapy trial were enrolled into an
intensive group of sulfonylureas or insulin vs. conventional control.”
“The drugs certainly were
successful in lowering blood sugars” [to 7.0% vs. 7.9% in the diet group], he
said, “but there was a price too. Weight gain was far worse on the drug
group….” But over the 10 years of the study, they found no “benefits for the
end points that everybody was interested in, i.e., cardiovascular disease (CV).
Despite reducing blood sugars, CV disease showed no benefits,” he averred.
“Since the majority of deaths are due to CV disease, the primary goal of
therapy was reduction in deaths and CV disease, not microvascular disease.”
In a sub-study called UKPDS34,
overweight patients with T2D were randomized to either metformin or diet
control alone. “Once again, over the space of over 10 years, the average blood
sugar was lowered by metformin to 7.4% compared to an average A1c of 8% in the
conventional group,” he said, but,
“In contrast to the previous study, intensive control with metformin showed a
substantial improvement in clinically important outcomes – there was a 36% decrease in death (all cause mortality)
as well as a 39% decrease in risk of
heart attack.”
“Metformin performed far better than the insulin/SU group
despite the fact that average blood sugar control was worse,” Dr. Fung
concluded (emphasis his). “What’s the major difference between the two
medication groups,” he asked? “Insulin! Insulin and sulfonylureas (SU) increase
insulin levels. Metformin does not.”
Refrain, all together now: “Because
it does not raise insulin, and insulin drives obesity, metformin does not cause
weight gain.”
Troubled by the failure of the
original UHPDS study to show a benefit from reducing high blood sugar in Type
2s, the U.S. National Institutes of Health (NIH) undertook “an ambitious large
trial called the ACCORD study (Action to Control Cardiac Risk in Diabetes).”
Two groups with an average A1c of 7.5% were randomly assigned, the 1st
to “standard therapy,” the 2nd to “intensive drug therapy,” “…with
the goal of seeing whether this intervention would reduce disease.” They were
successful in lowering their A1c to 6.5%.
But that was not the primary end
point. They “wanted to know whether this made any difference. It sure did,” Dr.
Fung says. “When the trial results broke, there was a media firestorm. Why?
Because the intensive treatment was killing people! The risk of death increased by a horrifying 21% in the
intensively treated group,” he wrote. Then, with 17 months before the
scheduled end of the trial, “the safety committee looked at the available data
and forced the premature end of the [ACCORD] trial.”
Was the study design flawed
because there was no specification of which medications to use to intensify
treatment, and the drug Avandia,
which was very popular at the time, was included? I took Avandia briefly before
I began to eat VLC. Avandia now carries a black label warning that it
may cause heart attacks, angina, and heart failure. “Yet, here we sit
in 2016, with no better idea of how to treat type 2 diabetes than to lower
blood sugars,” Dr. Fung concludes.
But Dr. Fung doesn’t leave the matter there. Check in tomorrow to see
what he suggests be done about it.
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