Introduction
Across the world, clinical problems
of obesity and type 2 diabetes (T2D) are crucial from various points of view
[1]. The standard guideline was presented by American Diabetes Association
(ADA) as Standards of Care in Diabetes-2023 in Jan 2023 [2]. Among them, recent
topics include clinical introduction of various types of oral hypoglycemic
agents (OHAs) for T2D and obesity [3]. Among them, these OHAs include
sodium–glucose cotransporter 2 inhibitor (SGLT2i) for T2D, CKD and heart
failure, dipeptidyl peptidase-4 inhibitor (DPP-4i), and oral route of
glucagon-like-peptide 1 receptor agonist (GLP1-RA). Oral semaglutide has been
developed, which seemed to show new era for novel peptide delivery [4]. It was
approved by US Food and Drug Administration (FDA) in US that has been
moderately used for actual medical practice [5].
In recent years, GLP-1RA has shown
higher demands, because of anti-obesity agents for social needs [6].
Consequently, oral semaglutide and liraglutide have led to some shortage and
then T2D treatment is so far prioritized [7]. Concerning clinical efficacy of
oral semaglutide as Rybelsus, large studies have been conducted for SUSTAIN and
PINONEER programs [8]. This fundamental investigation associated with clinical
research had led to the results of PIONEER, which stands for Peptide InnOvatioN
for Early diabEtes tReatment [9].
Authors and research group have
presented lots of reports concerning diabetes and endocrine diseases. Among
them, several themes were included, such as OHAs, diet therapy, meal tolerance
test (MTT), Carbo-70g loading test, low carbohydrate diet (LCD), continuous
glucose monitoring (CGM) and others [10,11]. Furthermore, recent studies were
about the administration of oral semaglutide as brand name Twymeeg [12-14].
During our daily medical practice, we recently experienced an impressive
patient with obesity and T2D. General clinical progress and related
perspectives are described in this article.
Case Presentation
History
and Physicals
The patient is a 41-year-old male working as a hospital staff for years. When he had annual health check in Jan 2020, HbA1c was 7.0% with 102kg in weight, 160cm in height and 39.8 kg/m2 in BMI. After that, HbA1c increased to 7.7% with weight 101kg in June 2020, and then he was advised to start medical treatment (Figure 1). He started nutritional therapy as petite-low carbohydrate diet (LCD), which includes 40% of carbohydrate amount per calorie calculation. Further, he initiated to take metformin 500mg per day. In Jan 2021, his HbA1c was 7.4% with weight 98kg. From his clinical progress, he was advised to start super-LCD meal every day. It means strictly limited LCD and has 12% of carbohydrate in the meal. His glucose variability and weight were improved 8 months later, showing HbA1c 5.7% and weight 91kg. Consequently, his nutritional therapy was changed from super-LCD to standard-LCD, which was 26% of carbohydrate in usual meal.
Figure 1: Clinical progress with HbA1c, weight, biochemistry and treatment.
Figure 2: Clinical progress
with HbA1c, weight, biochemistry and treatment
2a: Fatty liver and Retention of gastric juice is observed.
2b: Pancreas showed no remarkable changes.
2c: Bilateral kidneys were un remarkable.
2d: Visceral fat and subcutaneous fat were increased.
His physicals were as follows: His
consciousness was alert and speech was normal. Vitals were stable with pulse
72, BP 132/ 85 mmHg, BT 36.4, respiration was normal with SpO2 99%.
He showed unremarkable findings as lung, heart, abdomen and neurological exams.
Abdominal circumference was 114 cm.
The blood chemistry of health
check-up in Feb 2022 showed as follows: Hb 14.6 g/dL, RBC 4.70 x 106
/?L, AST 19 U/L, ALT 34 U/L, GGT 38 U/L (-79), total-Cho 243 mg/dL, HDL-C 57
mg/dL,? LDL-C 158 mg/dL, TG 141 mg/dL. Chest X-ray was
negative, and ECG showed within normal limits.
Clinical
progress
This case showed the improvement of
HbA1c and body weight during June 2020 to Jan 2022. However, his HbA1c and
weight have increased again as 6.4% and 92kg in March 2022. Consequently, he
started to take oral semaglutide (Rybelsus) 3mg/day. His general situation was
improved as HbA1c 5.5% weight 88kg and BMI 34.3 kg/m2 in Nov 2022.
His nutritional therapy was continued by standard-LCD. In Jan 2023, ALT as
liver function showed reduced level of 27 U/L, associated with improved HbA1c
and weight.
Concerning his radiological data, he
received abdominal CT scan in Sept 2022. The results were shown in Figure 2, in
which fatty liver, and retention of gastric juice, unremarkable changes in
pancreas, unremarkable bilateral kidneys and increased visceral / subcutaneous
fat were observed.
Ethical Considerations
This case study was carried out along
with the ethical principles from the Declaration of Helsinki. Moreover, several
comments were considered as the Ethical Guideline for Human Research and the
Good Clinical Practice (GCP). Authors et al. have established the current
ethical committee as to this report. This committee is present in our hospital
with several professionals. They include the president of the hospital,
physician in charge, head nurse, pharmacist, registered dietitian, and also
legal specialty. Satisfactory discussion was conducted in their attendance.
Consequently, agreement was fully given for the current protocol. The informed
consent was obtained from the patient by the document.
Discussion
The current case is a 41-year-old man
with obesity and T2D. His general situation was improved for HbA1c and body
weight by continuing LCD and administration of imeglimin (Rybelsus). The
important points for the discussion seem to be as follows: i) clinical effect
of imeglimin, ii) super-LCD and weight reduction, and iii) improvement of
complication such as fatty liver. The discussion will be described in this
order.
First, several OHAs have been used
for T2D in recent medical practice. Among them, a topic includes oral
semaglutide (Rybelsus) as GLP-1RA associated with clinical efficacy [15]. It
was developed for continuous pharmacological research for 30 years [16].
Regarding the important aspect, it can be synthesized by sodium
N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC) which is one of the absorption
enhancers [17]. Because this peptide can be administered per os, it would be
the important cornerstone for novel drug delivery system (DDS) in the future
[18]. Further, clinical effects of Rybelsus include not only anti-diabetic
efficacy but also beneficial efficacy on cardiovascular axis [19]. From mentioned
above, peptide research field can develop associated with such SNAC matter
[20]. For actual practice, Rybelsus was approved by United State FDA, EMA and
PmDA [21]. Various evidence was reported by useful investigation of PIONEER
[8].
Second, authors et al. have developed
LCD development medically and socially for long through Japan LCD promotion
association (JLCDPA) [22]. From historical point of view, Dr. Atkins has
initiated LCD [23]. LCD has been known to be effective from the large
investigation of Dietary Intervention Randomized Controlled Trial (DIRECT)
[24]. Authors and collaborators have presented actually useful LCD meal methods
[25]. Their type are super-LCD, standard-LCD and petite-LCD, in which
carbohydrate amount ratio are 12%, 26% and 40%, respectively. When intake
calorie is 1600kcal per day, carbo calories is calculated as 1600kcal x 0.12 =
168 kcal, and then 168kcal/ 4kcal (carbo 1g) equals 42g of carbohydrate a day.
Third, using super-LCD, we have
achieved remarkable weight reduction in many cases of obesity and T2D [26].
Authors have applied these 3 types of LCD for various patients, and showed
satisfactory results. Among more than 2900 cases, 25% cases have achieved more
than 10% of weight reduction [27]. LCD has remarkably decreased serum level of
triglyceride [28]. In addition, it shows improvement of fatty liver disease
with the study of Randomized Controlled Trial (RCT) [29]. Furthermore, LCD may
be involved in the ketogenesis and ubiquitination [30].
Limitations may the present in the
current report. It is only one case with obesity and T2D for the improvement by
Rybelsus and super-LCD. Future clinical progress would be carefully followed
up, including macroangiopathy, microangiopathy and other complications [31].
In summary, rather younger male patient showed the decrease of HbA1c and
weight. Clinical effects seemed to be from oral semaglutide and super-LCD.
Current report becomes hopefully a useful reference for diabetic research in
the actual practice.
Conflict of Interest
The authors declare no conflict of interest.
Funding
There was no funding received for this paper.