Oral semaglutide has been
evaluated to be useful and beneficial agent for the treatment of T2D and
obesity as Rybelsus [11]. It was synthesized by the pharmacological development
with absorption enhancer, that is sodium N-(8-[2-hydroxybenzoyl] amino)
caprylate (SNAC) [12]. It became the cornerstone for historical pharmaceutical
situation, because the peptide can be administered per os [13]. Furthermore,
oral semaglutide revealed cardiovascular (CV) efficacy and safety, and showed
the similar situation compared with subcutaneous administration [14].
Consequently, SNAC may be one of the drastic agent for future drug delivery
system (DDS) [15].
For our actual medical
practice, some GLP-1RAs have been used [16]. Their types were classified in the
following: a) oral semaglutide once daily for novel type of formulation, b)
subcutaneous once weekly as semaglutide, duraglutide and exenatide, c)
subcutaneous twice a day as exenatide, and d) subcutaneous once daiy:
lixenatide and liraglutide. Among these kinds of administration, oral intake
seemed to be simple and useful. From clinical effect point of view, oral
semaglutide has contributed improvement of T2D and also obesity [17]. Large
clinical studies were conducted for Rybelsus, including Peptide InnOvatioN for
Early diabEtes tReatment (PIONEER) and Semaglutide Treatment Effect in People
with Obesity (STEP) [8]. They revealed that the agent has gastrointestinal
adverse events (GIAEs), but the degree was not so severe.
In this case, 72-year-old
male patient has showed gradual elevation of body weight, HbA1c, liver function
of ALT and GGT for a few years. He has medical problems including T2D, fatty
liver, hypertension and orthopedic arthralgia. For the purpose of his
treatment, the improvement of T2D and obesity would be indispensable.
Consequently, oral semaglutide (Rybelsus) was suitable agent. As a matter of
fact, his weight and HbA1c were decreased enough for short period, indicating
satisfactory clinical efficacy. He did not feel any GIAE. He can tolerate
Rybelsus well associated with general improvement. Like this case, T2D patients
often have obesity and fatty liver, and then Rybelsus may contribute clinical
improvement of these problems [18].
This case has T2D and
hypertension, which indicates the existence of arteriosclerotic cardiovascular
disease (ASCVD). Concerning ASCVD and semaglutide, seven cardiovascular outcome
trials (CVOTs) were investigated. It included 56 thousand cases, and
semaglutide group revealed lower odd ratio (OR) for less CV death [19]. The
data showed 0.47 of exenatide, 0.46 of dulaglutide, 0.45 of albiglutide and
0.43 of lixisenatide. These results suggested the beneficial efficacy of
semaglutide for ASCVD. Another report was found as to 9890 cases from 11 RCTs.
They showed the superior clinical effect of semaglutide than other GLP-1Ras
[20]. As a result, the difference of weight and HbA1c was 1.48kg and 0.35%,
compared with empagliflozin, liraglutide and sitagliptin groups. Actual reduction
data in semaglutide group were 2.99kg and 0.89%, respectively which were
satisfactory degree. When this predominance was calculated for OR, which showed
OR 0.55 in CV mortality and OR 0.58 in all-cause mortality.
Clinical efficacy of
semaglutide for CV risk was shown from the data of PIONEER and SUSTAIN [21]. As
to semaglutide group and comparator group, several factors were compared as
hazard ratio (HR). There were 3 risk groups among them as higher 95%, middle
50%, lower 5%, in which HR was 0.84, 0.62, 0.45, respectively. For the middle
CV risk, semaglutide vs comparator groups revealed the results: HbA1c 7.2% vs
10.3%, systolic blood pressure 137 mmHg vs 163 mmHg, LDL-C 124 mg/dL vs 151
mg/dL, eGFR 91.7 mL/min/1.73m2 vs 94.1 mL/min/1.73m2,
respectively. Thus, semaglutide group showed lower risk of major adverse
cardiovascular events (MACE) in the T2D cases [21].
Some limitation may be
found in the case report. This is only one case with T2D, obesity and fatty
liver, who took oral semaglutide. He showed satisfactory clinical improvement
of weight and HbA1c, without any GIAEs. However, longer clinical progress will
be followed up from several points of view in the course. They include T2D,
body mass index (BMI), liver function tests, renal function, macroangiopathy of
cerebral vascular accident (CVA), CVD and peripheral artery disease (PAD) [22].
In summary, elder male revealed remarkable improvement of weight and HbA1c,
liver function by oral semaglutide (Rybelsus). This report is expected to be a useful
reference, beneficial to diabetic research and practice in the future.
Conflict of Interest
The authors declare no
conflict of interest.
Funding
There was no funding
received for this paper.
