00:01
In this case, a 57-year-old man presents to his
primary care physician for follow-up of his
diabetes. He has been diagnosed with type 2 diabetes
3 months ago and has been started on metformin
and lifestyle modifications. The patient does
not have any current complaints except for occasional
numbness in both hands and feet. His hemoglobin
A1c is 8.5% and his serum glucose is 240 mg/dL.
00:28
What is the best next step for managing this patient?
The best next step is to obviously add a
second agent to treat his diabetes. Once lifestyle
modifications have been initiated and metformin
has been started and dose maximized, if the patient
continues to have elevations of hemoglobin
A1c and serum glucose, a second oral agent is
usually indicated. Second line therapy for type 2
diabetes after dosing metformin. After initiating
metformin, if the hemoglobin A1c remains above
goal, the best next step is to add a basal insulin
or a non-insulin agent. This table overviews
most of the non-insulin diabetes medications
that are important. Starting with the sulfonylureas,
an example being glipizide. Adverse effects with
these agents are weight gain and hypoglycemia
as well as rashes. Effect on weight is to increase
the weight and should be used with caution in
patients whose renal clearance is decreased as in
kidney failure. This will prolong the action
of the medication and result in hypoglycemia.
Metformin is listed here. The adverse effects that
one encounters include diarrhea and abdominal pain.
Also note that lactic acidosis is an unusual
but worrisome side effect of metformin and usually
is increased in the setting of those patients
who are going for intravenous contrast testing.
So please be aware of this and recommend that the
patient stop taking the metformin before their
radiologic procedure. Effect on weight of metformin
is usually to decrease it but taking and aggravating
it is usually neutral. Caution in use of
metformin should also be exercised in patients with
renal dysfunction. But as you can see here,
the glomerular filtration rate has to be fairly low
less than 30 mg/min in order for the metformin
dose to be decreased. In fact, there is evidence
now that dosing patients with moderate or
mild renal insufficiency with metformin improves
their overall outcomes. The alpha glucosidase
inhibitors include agents like acarbose. These are
medications that promote carbohydrate excretion
from the gastrointestinal tract. Unfortunately,
owing to its mechanism of action, adverse effects
include abdominal discomfort. Effect on weight
is neutral and this medication should also be
avoided with kidney dysfunction. The thiazolidinediones,
examples of which include the glitazone
family of medications can cause weight gain,
they can cause heart failure. They have been associated
with macular edema and bone problems as well as
bladder cancer. They also increase weight
and caution should be exercised in patients who
have cardiovascular disease because of a higher
documented mortality in the case of rosiglitazone,
one of the medications within this class of drug.
03:31
The mitiglinides, which include repaglinide,
also has the adverse effect of weight gain and low
glucose and should be moderated in patients whose
kidney is not functioning normally. The
amylinomimetic class of agents have adverse
effects of nausea and vomiting but they do have
a positive effect on weight. They should also
be used with caution in patients who have hypoglycemia
especially in conjunction with insulin.
The glucagon-like peptide mimetics like Exenatide also
have nausea and vomiting as adverse effects
but positive effects on weight. Unfortunately, there is
an increased risk of pancreatitis and kidney
failure with this class of drug. The dipeptidyl
peptidase inhibitors like sitagliptin also cause
nausea, rash, and can lead to the high incidence
of infections. They have a neutral effect on
weight and unfortunately because of their mechanism of
action can cause pancreatitis and heart failure.
And then finally, the sodium glucose transporters
such as the gliflozin family of drugs. They
increase the incidence of fungal infections and can
cause urinary tract infections but have a
positive effect on weight. The caution should be exercise
with using these drugs because of increased
hypoglycemia risk when used in conjunction with insulin.
05:01
Also use caution when patients have a history of
peripheral vascular disease. Choosing agents
for diabetes management. The general principles
here revolve around the patient's weight. As you can
see from the evaluation of all of the medications,
all the different agents have variable effects
on patient's weight control ranging from increasing
weight to decreasing weight to neutral effects.
05:26
The weight-neutral drug classes include
the alpha glycosidase inhibitors like acarbose and the
dipeptidyl peptidase 4 inhibitors. If weight
loss is the desired effect, consider glucagon-like
peptide 1 or the GLP-1 mimetics like pramlintide
or sodium glucose transporter 2 inhibitors like
the Gliflozin family of drugs. Weight gain is
likely with the use of insulin, sulfonylureas,
thiazolidinediones, and mitiglinides.