Prescribing GLP-1 Receptor Agonists for Weight Loss
LEE-SHING CHANG: Hi, my
name is Dr. Lee-Shing Chang and I'm an associate
physician and endocrinologist at Brigham & Women's Hospital
in Boston, Massachusetts. In this video, we'll be talking
about GLP-1 receptor agonists and their use in weight loss. Key takeaway points
from this video are– to understand indications,
contraindications, and cautions for use of GLP-1 receptor
agonists in weight loss; and to understand the
dosing, administration, and side effects of
GLP-1 receptor agonists when used for weight loss. Liraglutide and
semaglutide are approved as an adjunct to a reduced
calorie diet and increased physical activity for
chronic weight management in adults with an
initial BMI, or Body Mass Index, in the obesity category,
which is considered at least 30 kilograms per meter squared,
or the overweight category with at least one weight
related comorbid condition such as hypertension, type
2 diabetes, or dyslipidemia.
There are several
conditions to be aware of that are
contraindications, or reasons to be cautious about
GLP-1 receptor agonist use. MEN2 which stands for multiple
endocrine neoplasia 2, or medullary thyroid
cancer, abbreviated as MTC are contraindications for use. This is because in
a rat model that was used to study GLP-1
receptor agonists, GLP-1 receptor agonist were
associated with an increased risk of C cell
cancer such as that seen in MEN2 or medullary
thyroid cancer correlates in humans. This has not been definitively
shown in humans, but because of this finding
in the rat model, there remains a warning
for use of GLP-1 receptor agonists in these populations.
Pregnancy is also
a contraindication for use of GLP-1
receptor agonists, because there are insufficient
data on their safety for use in pregnancy. There are also
several conditions to be aware of for which
GLP-1 receptor agonist should be used with caution. In patients with known or
active gallbladder disease, caution should be exercised
because GLP-1 receptor agonists are associated
with a higher risk of gallbladder-related
adverse events, including cholecystitis
and cholelithiasis. In patients with a
history of pancreatitis, GLP-1 receptor
agonist should also be used with caution
because some studies showed a potential increase signal for
adverse pancreatitis related events, although this has
not been definitively proven. In patients with retinopathy,
GLP-1 receptor agonists have been associated
with an increased risk of adverse
retinopathy outcomes.
This is thought to be
related to the rapid decrease and improvement in glucose
in patients treated with GLP-1 receptor agonists. Consider consulting with
a patient's optometrist or ophthalmologist
if you're considering starting a GLP-1 receptor
agonist in someone with retinopathy. GLP-1 receptor agonist
can delay gastric emptying and this is a reason for
caution for use in patients with gastroparesis or
delayed gastric emptying, as GLP-1 receptor agonist
use can potentially worsen symptoms of gastroparesis. And finally, in patients who
are on concurrent insulin or insulin secretagogues,
such as sulfonylureas, you should be aware
of GLP receptor use because it may be associated
with increased hypoglycemia risk. In and of themselves
GLP-1 receptor agonists have a low risk of hypoglycemia,
but when used in combination with medications that
can cause hypoglycemia, GLP-1 receptor agonist may
potentiate hypoglycemia risk. In a patient who has
well-controlled diabetes who's on insulin or a sulfonylurea,
consider proactively reducing the insulin and/or sulfonylurea
doses when starting a GLP-1 receptor agonist. Let's turn to the practical
use and administration of GLP-1 receptor agonists. Liraglutide and semaglutide
for weight management are both subcutaneous
injections given in the abdomen, the thigh, or the upper arm.
If doses are given
in the abdomen, generally we recommend
at least 2 inches away from the belly button. They can be given in
the front of the thighs or the posterior upper
arms, and the upper arm is a particularly good location
if another person is helping administer the injection. Both medications come
in pens, but there are some important
differences between the pens. Liraglutide contains
multiple doses per pen, while semaglutide
for weight management comes in a one time use pen. Liraglutide requires
a separate pen needle to be used each time
an injection is given.
This is screwed on
at the end of the pen and disposed of after each use. Be aware that the pen
needles for liraglutide need to be prescribed
and purchased separately from the pen prescription. Semaglutide has an
auto injector mechanism where the pen needle is built
in and automatically retracts after use. To set the dose for
liraglutide, the pen has a dial that can be twisted
to the appropriate dose. In comparison, semaglutide
for weight management has a preset dose per pen. For both liraglutide
and semaglutide for weight management,
the dose should be started at the lowest
dose and slowly titrated up.
Higher doses are associated
with higher weight loss, but also with a greater risk of
gastrointestinal side effects. For liraglutide, the
daily dose is typically increased by one increment
every one week as shown here. If a patient is doing
well with the medication, they should reach the maximum
dose of 3 milligrams daily by week 5. For semaglutide, the
weekly dose is typically increased by one increment
every four weeks as shown here. If a patient is doing
well with the medication, they should reach the maximum
dose of 2.4 milligrams weekly by week 17. Note that with semaglutide,
a new prescription is needed for each new dose
because the pens are prefilled with a single dose. For your information, the colors
in the semaglutide section here match the
actual pen colors. Gastrointestinal
side effects are very common with GLP-1
receptor agonists. These are likely due to
the central nervous system effects on decreasing
appetite, as well as the gastrointestinal effects
on slowing gastric emptying. Side effects are particularly
common after the initial dose and within the first four or so
weeks of medication initiation. They typically subside
with continued doses of the medication. And these side effects can
include nausea and vomiting, abdominal pain,
bloating, constipation, or on the opposite end, diarrhea
early satiety, and heartburn.
It can be very helpful to set
expectations with the patient and give them
anticipatory guidance about these common
gastrointestinal side effects. They tend to be mild
to moderate, transient, and dose dependent. That's why we start
low and go slow with up titration of the
medications to get the body used to each new
dose of the medication. These gastrointestinal
side effects typically improve over the
first few weeks, for example, the first
four to six weeks of use. Giving patients tips can
also be helpful to reduce the risk of these side effects. For example, eating
smaller portions, counseling them to stop
eating before they feel full, avoiding fried, greasy,
or oily foods which may be more likely to trigger
some of these side effects, and staying well
hydrated with water. Use of GLP-1 receptor
agonist for weight management and treatment of overweight and
obesity is a very hot topic, and it's worthwhile to be on
the lookout for ongoing studies as the field is
rapidly evolving.
I've highlighted a
few specific areas to be aware of in the
coming years here. Cardiovascular outcomes
trials are underway for weight loss medications
such as the SELECT trial for semaglutide to assess
the cardiovascular safety with weight loss
pharmacotherapy. Additionally,
several novel classes of medications incorporating
GLP-1 receptor agonists have shown significant
promise for weight loss. Twincretins are combination
GLP-1 receptor agonists with GIP receptor agonists. And GIP is gastric
inhibitory peptide which is also known as glucose
dependent insulinotropic polypeptide. Combining GIP with
GLP-1 receptor agonists seems to result in even
greater weight loss and the first SURPASS
series of trials was published in 2021
showing significant weight loss with this.
Finally, two other molecules in
combination with GLP-1 receptor agonist seem to also
have potential roles in weight management. These are amylin analogs and
glucagon receptor agonists. For example, cagrilintide is
a long acting amylin analog that is being studied in
combination with semaglutide and shows promising
initial results. Of note, tirzepatide
and cagrilintide have not yet been
FDA approved for use. Thank you so much
for watching, I hope you found
this topic helpful..
