Dialogue and Diagnosis - American Osteopathic Association

missed and the next scheduled dose
is less than 3 days from the current
time, the patient should wait until
the next regularly scheduled dose to
restart the medication. 44
Are there oral forms
of GLP-1 receptor
agonists?
Many patients are aware that several
new drugs are available to manage
the hyperglycemia of T2DM. Represented
prominently in the AACE
treatment algorithm 9 are DPP-4
inhibitors, primarily because of their
good tolerability and low risk of
hypoglycemia. However, important
differences exist between that class
of incretin-based medications and
GLP-1 receptor agonists. The DPP-4
inhibitors work to inhibit the enzyme
that degrades GLP-1. Although DPP-4
inhibitors may inhibit the degrada -
tion of GLP-1, many patients with
T2DM have an impaired incretin
effect, so ambient GLP-1 levels may
already be compromised in these
individuals. 49 This compromised
condition may partly explain the difference
in glucose-lowering potential
between DPP-4 inhibitors and GLP-1
receptor agonists, in favor of GLP-1
receptor agonists, 29,50,51 which
directly provide GLP-1 agonism at
pharmacologic or supraphysiologic
levels. 52 The DPP-4 inhibitors primarily
affect postprandial glucose
levels. 53
The differences in effects on GLP-1
levels may partly explain the
differences in weight effects between
GLP-1 receptor agonists and DPP-4
inhibitors. 29,33 Recent data suggest
that a reduced incretin effect and
fasting hyperglucagonemia may constitute
early steps in the pathophysiologic
development of T2DM,
detectable even in obese people who,
despite their insulin-resistant state,
have normal glucose tolerance. 54
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