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Newer doesn’t mean better when it comes to
Type 2 Diabetes Drugs
Newswise, March 16, 2011 — An inexpensive
type 2 diabetes drug that has been around
for more than 15 years works just as well
and has fewer side effects than a half-dozen
other, mostly newer and more expensive
classes of medication used to control the
chronic disease, new Johns Hopkins research
In their report, published online March 14
in the journal Annals of Internal Medicine,
the Hopkins team found that metformin, an
oral drug that was first approved by the
U.S. Food and Drug Administration in 1995,
not only controlled blood sugar, but was
also less likely to cause weight gain or
raise cholesterol levels.
“Metformin works for most people. It’s
cheaper, there’s a generic form — it’s tried
and true,” says study leader Wendy L.
Bennett, M.D., M.P.H., an assistant
professor in the Division of General
Internal Medicine at the Johns Hopkins
University School of Medicine. “Our study
shows that even though there are all these
newer drugs, metformin works just as well
and has fewer side effects.”
The study is an update of Hopkins research
published in 2007 that also showed there
were advantages to metformin.
New classes of medication for adult-onset
diabetes have been approved by the FDA since
then, and Bennett and her colleagues wanted
to know if the newer drugs were any better
than the older crop.
The research team also looked for the first
time at the efficacy of two-drug
combinations to treat the chronic disease,
which has become increasingly common with
more than one-third of diabetes patients
needing multiple medications.
Researchers found that while two drugs
worked better than one in those patients
whose blood sugar remained poorly controlled
on a single medication, there were also side
effects associated with adding a second
“Diabetes is an enormous public health
problem, and patients have difficult
decisions to make about what medications
they should be taking,” Bennett says. “Our
study provides good information comparing
drugs and can be used to inform those
Bennett and her colleagues reviewed 166
previously published medical studies that
examined the effectiveness and safety of
diabetes drugs, as well as their impact on
long-term outcomes including death,
cardiovascular disease, kidney disease and
The team had previously looked at several
popular classes of oral diabetes medication
— metformin (sold as Glucophage, Fortamet
and others), second-generation sulfonylureas
(Amaryl, Glucotrol and more),
thiazolidinediones (Avandia and Actos) and
meglitinides (Starlix and Prandin) — and
added two new classes of drugs, dipeptidyl
peptidase-4 (DPP-4) inhibitors (Januvia and
Onglynza) and glucagon-like peptide-1
(GLP-1) receptor agonists (Byetta and
Victoza), which are given by injection.
No drug or combination of drugs was shown to
have an advantage in improving long-term
outcomes, Bennett says, primarily because
there weren’t enough long-term studies,
particularly of newer medications.
While most drugs reduced blood sugar
similarly, metformin was consistently
associated with fewer side effects.
Though metformin is associated with
increased risk of gastrointestinal side
effects, Bennett, an internist, says she
finds many of her patients can overcome them
by starting with a low dose and taking it
with meals, though patients with severe
kidney disease may avoid it.
The sulfonylureas and meglitinides were
associated with increased risk for
hypoglycemia, or dangerously low blood sugar
levels. The thiazolidinediones increased
risk of heart failure, weight gain and
In September 2010, the FDA placed
restrictions on the use of Avandia because
of concerns that the drug increases the risk
of heart attack.
Meanwhile, the new medications, because
there are no generic options, are
significantly more expensive than older
One hundred metformin pills cost about
$35.57, or 35 cents a pill, while 30 Januvia
pills (a DPP-4 inhibitor) cost $192.52, or
$6.42 a pill — nearly 18 times as much.
While the drugs all reduce blood sugar
levels, Bennett says more research is needed
into whether they actually improve outcomes
for diabetics in the long run.
It remains an open question as to whether
patients with type 2 diabetes who have their
blood sugar controlled by medication will
reduce their chances of having complications
associated with the disease, including eye,
kidney and nerve diseases, she says.
“Some of the drugs haven’t been on the
market long enough to study the long-term
effects or even some of the short-term rare
side effects, so we need longer studies in
patients who are at highest risk for
complications” she says.
More than 25 million Americans have type 2
diabetes, and the number of diagnoses have
been steadily rising, with 1.9 million new
cases diagnosed in 2010. Like many chronic
illnesses, diabetes disproportionately
affects older people, and its prevalence is
higher among racial and ethnic minorities.
The annual economic burden of diabetes is an
estimated $132 billion and increasing,
mostly attributable to costly complications
of the disease.
The study was paid for by the U.S.
Department of Health and Human Services’
Agency for Healthcare Research and Quality.
Along with Bennett, other Hopkins
researchers involved in this work include
Nisa M. Maruthur, M.D., M.H.S.; Sonal Singh,
M.D., M.P.H.; Jodi B. Segal, M.D., M.P.H.;
Lisa M. Wilson, Sc.M.; Spyridon S.
Marinopoulos, M.D., M.B.A.; Milo A. Puhan,
M.D., Ph.D.; Padmini Ranasinghe, M.D.,
M.P.H.; Lauren Block, M.D.; Susan Hutfless,
Ph.D.; and Eric B. Bass, M.D., M.P.H.