Revista multidisciplinaria
Investigación Contemporánea 01 - 2025 Vol. 3 - No. 1 ISSN-e: 2960-8015
Bibliographic review. Revista multidisciplinaria investigación Contemporánea.
Vol. 3 - No. 1, pp. 53 - 71. January-June, 2025. e-ISSN: 2960-8015
Sodium glucose cotransporter 2
inhibitors (SGLT2i) in the treatment
of type 2 diabetes mellitus: Literature
review
Inhibidores del cotransportador de sodio y glucosa tipo
2 (SGLT2i) en el tratamiento de la diabetes mellitus tipo
2: revisión de la literatura
1 Universidad de Cuenca; orellana_28@outlook.com. Cuenca, Ecuador.
2 Universidad de Cuenca; anto.1996gm@hotmail.com. Cuenca, Ecuador.
3 Ministry of Public Health; erigabyeo99@gmail.com. Cuenca, Ecuador.
4 Diálisis Prodial Santiago de Chile; pedro.jfb@hotmail.com. Santiago de Chile, Chile.
Bryan Andrés Orellana Tapia 1*, Antonella Fernanda Gallegos Mora 2, Erika Gabriela
Córdova Orellana 3, Pedro José Flores Brito 4
DOI: https://doi.org/10.58995/redlic.rmic.v3.n1.a84
How to cite:
Orellana Tapia BA, Gallegos Mora AF, Córdova Orellana EG, Flores Brito PJ. Sodium glucose cotransporter 2
inhibitors (SGLT2i) in the treatment of type 2 diabetes mellitus: Literature review . REVMIC [Internet]. 2024 Oct.
22 [cited 2024 Oct. 22];3(1). Available at: https://doi.org/10.58995/redlic.rmic.v3.n1.a84
Article information:
Received: 25-04-2024
Accepted: 04-09-2024
Published: 15-01-2025
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and institutional afliations.
Publisher:
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Sources of nancing:
The research was carried out with own resources.
Conicts of interest:
No conicts of interest.
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Revista multidisciplinaria
Investigación Contemporánea 01 - 2025 Vol. 3 - No. 1 ISSN-e: 2960-8015
DOI: https://doi.org/10.58995/redlic.rmic.v3.n1.a84
Sodium glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of
type 2 diabetes mellitus: Literature review 54 - 71
Summary
Diabetes mellitus is a chronic disease that affects the world's population. In Latin America, the
prevalence rates are high and mortality is increasing. In Ecuador, in 2017, 4,895 deaths were
reported due to this disease. Sodium-glucose cotransporter inhibitors (SGLT2 inhibitors)
have been shown to be suitable for the treatment of diabetes mellitus. They help reduce body
weight and glycosylated hemoglobin, especially in patients with good kidney function. SGLT2
inhibitors, approved in recent years, block the renal reabsorption of glucose, promoting its
excretion through urine. This reduces blood glucose and offers additional benets such as
kidney protection and decreased cardiovascular risks. Methodology: non-experimental,
bibliographic review. Objective: To analyze the overall benets of SGLT2 transporter
inhibitors in the treatment of type 2 diabetes mellitus. Results : The main SGLT2 inhibitors
each with specic pharmacokinetic characteristics and therapeutic applications that can
be taken advantage of when treating patients with diabetes mellitus. Conclusions : Type 2
diabetes mellitus is a chronic pathology that merits timely and adequate treatment with drugs
that have clinical benets for the patient. Taking into account SGLT2 inhibitors, diabetic
patients can be provided with a novel treatment that is generally well tolerated according to
the patient's conditions.
Keywords : Diabetes mellitus, diabetes complications, ISGLT2.
Resumen
La diabetes mellitus es una enfermedad crónica que afecta a la población mundial. En
América Latina, las tasas de prevalencia son altas y la mortalidad va en aumento. En
Ecuador, en 2017, se reportaron 4.895 muertes por esta enfermedad. Los inhibidores
del cotransportador de sodio-glucosa (inhibidores de SGLT2) han demostrado ser
adecuados para el tratamiento de la diabetes mellitus. Ayudan a reducir el peso
corporal y la hemoglobina glicosilada, especialmente en pacientes con buena
función renal. Los inhibidores de SGLT2, aprobados en los últimos años, bloquean
la reabsorción renal de glucosa, promoviendo su excreción a través de la orina.
Esto reduce la glucosa en sangre y ofrece benecios adicionales como protección
renal y disminución de riesgos cardiovasculares. Metodología: revisión de literatura
no experimental. Objetivo: Analizar los benecios globales de los inhibidores del
transportador SGLT2 en el tratamiento de la diabetes mellitus tipo 2. Resultados: Los
principales inhibidores de SGLT2 tienen cada uno características farmacocinéticas
especícas y aplicaciones terapéuticas que pueden aprovecharse al tratar a pacientes
con diabetes mellitus. Conclusiones: La diabetes mellitus tipo 2 es una patología
crónica que amerita un tratamiento oportuno y adecuado con fármacos que aporten
benecios clínicos al paciente. Teniendo en cuenta los inhibidores de SGLT2, se puede
brindar a los pacientes diabéticos un tratamiento novedoso que en general es bien
tolerado de acuerdo a la condición del paciente.
Palabras clave: Diabetes mellitus, complicaciones de la diabetes, ISGLT2.
Revista multidisciplinaria
Investigación Contemporánea 01 - 2025 Vol. 3 - No. 1 ISSN-e: 2960-8015
DOI: https://doi.org/10.58995/redlic.rmic.v3.n1.a84
Sodium glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of
type 2 diabetes mellitus: Literature review 55 - 71
1. Introduction
Diabetes mellitus is a serious public health problem that brings with it multiple
complications that can even be fatal. Currently, approximately 463,000,000
people between 20 and 79 years of age suffer from this pathology, which
represents 9.3% of the population around the world. It is expected that by 2030
this number will increase to 578,000,000 (10.2%) and in 2045 to 700,000,000
(10.9%). The importance of prevalence lies in identifying the population that
has the highest risk of developing the disease, greater impact on their quality of
life and premature mortality (1).
It is a pathology of great signicance, since in Latin America and the
Caribbean the prevalence is high, for example, Mexico has a prevalence of 10.7%,
Bogotá 10%, Guatemala 8%. In Ecuador the mortality rate has increased in
recent years due to this pathology, in 2017 a total of 4895 deaths were reported
(2).
Likewise, according to data from the WHO (World Health Organization),
66% of diabetics suffer from some type of disability compared to 29% who do
not suffer from this pathology, demonstrating its importance in the quality of
life of the population that suffers from it. Gomezcoello et al (3) showed that the
prevalence of diabetes mellitus in the Enrique Garcés General Hospital in older
adults was 14%, it is worth mentioning that the majority presented chronic
complications that were related to longer duration of the disease along with
higher values of H b A1C (glycosylated hemoglobin).
Sodium-glucose cotransporter inhibitors, also known by their acronyms
as iSGLT, are drugs that have a series of benets for the body of a diabetic
patient. Lytvyn et al. (4) indicate that iSGLT help to reduce 2-3kg of body weight
by blocking glucose reabsorption, and also reduce glycosylated hemoglobin
values by an average of 0.7%. It should be noted that this reduction is more
evident in patients who have proper kidney function.
In the search for drugs that provide protection in renal function, trials
have been carried out with inhibitors of the renin-angiotensin-aldosterone
system and endothelin receptor antagonists, the results of which were not
favorable, which is why the use of iSGLT is motivated since these do provide
renal protection. High levels of glycemia or insulinemia can cause kidney
Revista multidisciplinaria
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Sodium glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of
type 2 diabetes mellitus: Literature review 56 - 71
damage due to hyperltration of the nephron or intraglomerular hypertension,
iSGLT2 by reducing glucose can prevent these entities that are common in
diabetic patients, taking into account that 40% of this group develops end-stage
renal disease (4).
The importance of knowing the therapeutic options for diabetes lies in the
high global prevalence and the public health problem that it entails.
The fact that doctors have the ability to make the diagnosis and provide
correct management is essential since it would be reected in a controlled
chronic disease and possible complications are minimized (5).
In patients suffering from diabetes, the incidence of myocardial infarction
and cerebrovascular events has decreased in the last 30 years; on the contrary,
terminal renal disease remains and its most frequent cause is diabetic
nephropathy (4).
2. Methodology
A literature research study was conducted using a bibliographic review method
with a qualitative approach of descriptive linking and with a non-experimental
design in which bibliographic sources such as PubMed, ScienceDirect and
Google Scholar were used. The information search was carried out using
keywords, which were taken from MES and DeCS. The terms that were selected
in DeCS were "Diabetes mellitus" AND "Diabetes complications" AND "ISGLT",
then the MESH terms "Diabetes mellitus" AND "Diabetes complications" AND
"ISGLT" were selected. After this, the review of the scientic articles according
to the research was carried out, the most relevant for the present study was
chosen and its results were evidenced to capture the present research. It is worth
mentioning that observational, descriptive, retrospective, prospective studies,
systematic reviews, bibliographic reviews and meta-analysis were used.
3. Development
Diabetes is a chronic metabolic disease associated with an unsatisfactory
prognosis and a high cost in controlling the disease. This disease is classied
into type 1 and type 2. Type 2 diabetes is a nutritional disorder generated by the
lack of response to the action of insulin resulting in high serum glucose levels,
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Sodium glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of
type 2 diabetes mellitus: Literature review 57 - 71
which could have complications such as kidney failure, diabetic retinopathy or
a high cardiovascular risk (6).
In 2017, its annual prevalence was 425 million worldwide and type 2
diabetes corresponds to more than 85% of the total cases. It is expected that by
2045 it will affect approximately 629 million people (6,7). It is widely distributed
throughout the world, however, there are certain patterns that determine a
greater or lesser prevalence, among these stand out age, sex, genes, ethnicity,
residence; these also inuence the type of diabetes to be presented, whether 1
or 2 (7).
In relation to the above mentioned, Forouhi & Wareham (7) establish
that diabetes is a public health problem that increases over time, and they also
indicate that this increase is due to the concomitance of a growing prevalence
of obesity, also associated with bad eating habits and low physical activity.
For this reason, numerous drugs have been developed in order to treat this
disease, however, it must be kept in mind that every treatment has its pros and
cons, which is why through the following research work, the characteristics,
pharmacokinetics, pharmacodynamics, mechanism of action, indications,
contraindications and adverse reactions that it produces will be analyzed (8).
The industrial revolution is advancing and the new thing on the market
is the sodium-glucose cotransporter 2 inhibitors, this type of drugs will reduce
the levels of glucose in the blood by blocking the renal reabsorption of glucose,
and its protective effect at the renal and cardiac level has also been recognized
(9).
In the 19th century, researchers discovered a substance extracted from the
apple tree that produces glucosuria, this is phlorizin. Interest in this compound
began around the 1950s, since it was shown that it blocks the transport of glucose
to some tissues, in which the kidney was found, which is why it was later used
to study the function of SGLT transporters. Phlorizin began to be evaluated for
therapeutic purposes when it was shown that there is excessive reabsorption of
glucose by the kidney, and this plays a role in the pathology of type 2 diabetes
mellitus, thus giving rise to selective SGLT2 inhibitor drugs (10).
Sodium-glucose cotransporter 2 inhibitors play important roles in the
aforementioned pathology such as glomerular hyperltration, renal hypoxia,
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Sodium glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of
type 2 diabetes mellitus: Literature review 58 - 71
its effect of reversibly reducing the glomerular ltration rate, in addition to
preserving the glomerular ltration rate in the future (9).
We must not forget that SGLT2 and SGLT1 are secondary active
cotransporters. SGLT2 perform reabsorption in the S1 and S2 segments of the
proximal tubule, unlike SGLT1, which do so in the S3 segment (9,11).(11)
SGLT2 transporter inhibitors
They are drugs capable of selectively and reversibly inhibiting the sodium-
glucose cotransporter (SGLT2), thus decreasing post-prandial hyperglycemia
(12). It is known that the kidney helps control plasma concentration levels,
physiologically the glomerular tuft lters 180 g /day/1.7m2 (healthy patient) and
represents 30% of the daily energy demand, which is absorbed in the proximal
tubules and returns to the blood mainly thanks to the type two glucose-sodium
cotransporters known as SGLT2 (8,9).
In patients suffering from diabetes, the glomerulus lters a greater
amount of glucose due to existing hyperglycemia. In this situation, the activity
of SGLT2 increases with the purpose of reabsorbing and returning to the blood
this amount of glucose present in the tubule, maintaining high blood glucose
levels (8,9).
As its name indicates, this type of medication fullls its role in inhibiting
the passage through these glucose-sodium cotransporters, ultimately leading
to the excretion of glucose through urine (8,9).
Thanks to the contribution of SGLT2, patients with type 2 Diabetes Mellitus
can excrete around 80% of glucose per day. Two things must be clear: rst, that
glucose reabsorption is carried out by SGLT2 in the proximal convoluted tubule
around 80-90%, second, that only the remaining 10% is done by SGLT1, which
has a lower afnity and concentration capacity, which is why there is a 100%
glucose recovery (9,11).
The use of SGLT2 is indicated exclusively for the management of type
2 diabetes mellitus, especially in the early stages of the disease. Nespoux (9)
mentions the use of empagliozin in diabetic patients with high cardiovascular
risks and in patients with an estimated glomerular ltration rate >30m L / min
/1.73m2. Finally, the role of SGLT2 is recognized, rst as a kidney protection
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Sodium glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of
type 2 diabetes mellitus: Literature review 59 - 71
agent and second, to prevent cardiovascular problems in patients with type
2 diabetes mellitus with a high risk. It can be used as dual therapies or triple
therapies together with insulin to treat patients with type 2 diabetes mellitus.
The use of SGLT2 inhibitors is contraindicated in the treatment of type 1
mellitus, and is not recommended for use in patients with severe renal failure,
or in patients with a glomerular ltration rate of less than 60 mL/min. (8). It
is important not to administer this type of medication in pregnant women,
which is why the FDA classies it within category C (medications that can be
used during pregnancy), leading to the development of kidney damage in the
fetus (8). Patients who use ASA or Pioglitazone diuretics are associated with
developing marked dehydration and even hypotension (9). It has been shown
that Dapagliozin should be contraindicated during breastfeeding (8).
Empagliozina
It is a drug that has a high selectivity in relation to SGTL2, an approximate half-
life of 23 hours, oral bioavailability greater than 60%, metabolism occurs thanks
to the glucuronidation process and around 75 grams of glucose are excreted
daily through urine (8,9).
Romera et al (13) analyzed the safety and efcacy of empagliozin plus
other oral hypoglycemic agents in an analysis of 3 trials that are in phase III
in patients with type 2 diabetes mellitus, they received placebo, empagliozin
10 or 25 mg every day for 24 hours in combination with metformin, metformin
± pioglitazone or metformin + sulfonylurea. It was shown that Empagliozin
in combination with other oral antidiabetics vs placebo helped to signicantly
reduce HbA1c, blood pressure, body weight with adequate tolerance and good
safety prole.
García et al (14) conducted a longitudinal, prospective study with 25
patients to whom empagliozin was administered gradually starting with a
dose of 10 mg orally every day for 4 weeks. Weight loss, elevated blood glucose
and decreased glycosylated hemoglobin were observed.
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Sodium glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of
type 2 diabetes mellitus: Literature review 60 - 71
Dapagliozin
It is the greatest exponent of the ISLGT2, it has been shown to be useful in
reducing HbAc1 and fasting glycemia in the long term having benecial results
for the patient, it has also been shown to reduce weight by causing glucosuria,
in addition to reducing systolic blood pressure by 5 mmHg. At doses of 2.5 -
50 mg every day for 12 weeks in patients with Diabetes Mellitus 2, it excretes
glucose in 52 - 85 mg. Caution should be taken when administering to patients
with cardiovascular diseases, moderate renal failure, shock or hypotension,
moderate dehydration (15).
The pharmacokinetic and pharmacodynamic characteristics are:
maximum plasma concentration at two hours, oral bioavailability at doses of
10 mg is 80% , the interaction of dapagliozin with high-fat foods reduces the
plasma concentration by half, and also prolongs the effect, it has the ability to
bind 85% with plasma proteins, it is metabolized thanks to the enzyme UDP-
glucuronosyltransferase 1-9, we must keep in mind that this unit will be found
at the renal and hepatic level (8,9).
Hidalgo et al (16) conducted a prospective observational study with
32 patients with type 2 diabetes mellitus before starting dapagliozin and
the patients were analyzed in follow-up at 6 and 12 months for biochemical
parameters in urine and blood and the carotid-femoral pulse velocity was
determined, demonstrating that there is a decrease in it, showing that it
produces a medium and long-term decrease in arterial stiffness.
On the other hand, Escudero et al (17) analyzed the results of seven
randomized clinical trials, two of which were used as monotherapy with 840
patients and ve as combined therapy with other oral antidiabetics (3184
patients). In all seven trials, dapagliozin helped reduce HbA1c levels compared
to placebo, except for one study in which the comparison was made against
glipizide. However, it should be noted that the present study concludes that
dapagliozin does not provide advantages with respect to pharmacotherapy
for type 2 diabetes mellitus due to the absence of important clinical benets
and the high cost.
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Sodium glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of
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Canagliozina
It is a drug administered as monotherapy, which is indicated in adults suffering
from type 2 diabetes mellitus when exercise and diet do not achieve the
objectives and the use of metformin is contraindicated. It can also be indicated
as a complementary treatment when administered with other medications
such as insulin or antihyperglycemic agents. The mechanism of action is the
reversible inhibition of the sodium-glucose cotransporter 2, thus decreasing
the reabsorption of glucose in the kidney, increasing urine, and thus decreasing
blood glucose (18).
It is rapidly absorbed, reaching its maximum concentration at 1-2 hours.
Absorption is not affected when administered with food, it is distributed mainly
with albumin (98%), and it is eliminated in feces and urine. It interacts with
rifampicin, digoxin and diuretics (18).
Ertugliozina
This drug has a half-life of 16 hours, has a bioavailability of 100%, has renal
(2%) and fecal (34%) excretion and has a hepatic metabolism (8,9).
Ipragliozina
Drug being developed in Japan. Doses between 50-300 mg as monotherapy every
24 hours were evaluated in patients with type 2 diabetes mellitus, and who have
not taken or are on previous treatment. Ipragliozime plus metformin was also
evaluated. As a result of these treatments, there was a quite signicant decrease
in blood glucose and glycosylated hemoglobin compared to placebo at 12-24
weeks. This drug as monotherapy decreased the weight of patients by 1.47 kg
at 16 weeks, as well as systolic blood pressure decreased by 3.2 to 4.3 mmHg
at 12-16 weeks. However, urinary tract infections occurred more frequently
compared to placebo (19).
Metha et al (20) conducted a study with a group of volunteers where the
following results were obtained: the maximum absorption of this drug was 1.5
to 2.1 hours, and the concentrations will decrease in a biphasic pattern. The
half-life is 13.1 hours. With a dose of 10 mg it will inhibit the reabsorption of
glucose by 40% of the ltered glucose and when high doses are given it can
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Sodium glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of
type 2 diabetes mellitus: Literature review 62 - 71
inhibit up to 60%. Studies show that there is no need to adjust the dose when
kidney function is impaired, and it has also been shown that it does not produce
signicant interactions with other medications.
Treatment with empagliozin vs sitangliptin monotherapy in patients
with type 2 diabetes mellitus who are not receiving treatment and with a
baseline HbA1c between 7-10% showed that the two drugs reduced glycosylated
hemoglobin equally. Empagliozin reduced weight, blood pressure and
abdominal circumference of patients more than sitangliptin. The rate of urinary
tract infections was similar with both drugs (20).
Tofogliozina
It is a selective SGLT2 inhibitor, which was approved in Japan as a treatment for
type 2 diabetes mellitus. A good efcacy and safety prole was demonstrated in
Japanese patients with diabetes mellitus (21).
In the study by Masayaku and Hisatako (21), s6897 patients were included
who took Apleway 20 mg tablet and Deberza 20 mg tablet (tofogliozin 20 mg
is usually given once a day orally before or after breakfast). The study lasted 12
weeks. Good results were shown, as it decreased the patients' HbA1c as well as
body weight. It was concluded that this drug is well tolerated, and signicantly
improved glycemic control (21).
Luseogliozina
It is a highly selective inhibitor of SGLT2, it was developed in Japan by “Taisho
Pharmaceutical” and approved for the treatment of type 2 diabetes mellitus in
2013. It is administered at a dose of 2.5 mg every day. In the study carried out
by Soichi Sakai and collaborators (22), which included 1031 patients with type
2 diabetes mellitus, and was stratied by the BMI they had, 2.5 mg daily was
administered (even up to 5 mg) in which the efcacy of the drug was attempted
to be veried by glycosylated hemoglobin , fasting plasma and body weight.
It was shown that HbA1c and body weight decrease in patients, as well as the
decrease in glycemia tends to be lower in patients with a BMI of 22.5 kg/m 2.
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Sodium glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of
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Table 1. Characteristics of the main SGLT2 transporter inhibitors in the treatment of
type 2 diabetes mellitus (23,24).(23)
Dapagliozin Canagliozina Empagliozina Ertugliozina
Dose
Initial dose 10 mg
orally every 24
hours.
Initial dose 100 mg
every 24 hours.
Dosis inicial
10 mg cada 24
horas. Dosis
máxima 25 mg
cada 24 horas.
Dosis inicial 5 mg
cada 24 horas.
Dosis máxima 15
mg cada 24 horas.
Side effects
Genital
infections,
urinary tract
infections,
increased
creatinine,
hypoglycemia,
nausea, vomiting,
constipation, low
back pain.
Genital fungal
infections,
hypercholesterolemia,
urinary tract
infections,
hypertriglyceridemia,
increased creatinine,
hypoglycemia,
orthostatic
hypotension, nausea,
vomiting, bone
fractures, asthenia,
pancreatitis.
Urinary tract
infections,
genital
infections,
hypovolemia,
hypoglycemia,
pruritus.
Urinary tract
infections,
polyuria, genital
infections,
hypoglycemia,
pruritus,
angioedema.
Maximum dose 25
mg every 24 hours.
Initial dose 5 mg
every 24 hours. Ertugliozin
Insuciencia
renal grave
(ltrado
glomerular
<30 mL/
min/1,73 m2),
pacientes en
diálisis o con
que padezcan
enfermedad
renal en etapa
terminal
Insuciencia
renal grave
(ltrado
glomerular <30
mL/min/1,73
m2), pacientes
en diálisis o con
que padezcan
enfermedad
renal en etapa
terminal
Contraindications
Contraindicated
in glomerular
ltration rate
<30 mL/min/1.73
m 2 .
severe renal
impairment
(glomerular ltration
rate <30 mL/min/1.73
m2 ) , patients on
dialysis or with end-
stage renal disease
Severe renal
insufciency
(glomerular
ltration
rate <30 mL/
min/1.73 m2
) , patients on
dialysis or with
end-stage renal
disease
Severe renal
insufciency
(glomerular
ltration rate
<30 mL/min/1.73
m2 ) , patients on
dialysis or with
end-stage renal
disease
Prepared by: authors of the work.
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Sodium glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of
type 2 diabetes mellitus: Literature review 64 - 71
4. Discussion
SGLT2 inhibitors have revolutionized the treatment of type 2 diabetes mellitus
by providing not only effective glycemic control but also cardiovascular and
renal benets. SGLT2i, such as empagliozin and canagliozin, have been
shown to be effective in reducing glycated hemoglobin (HbA1c) levels (25,26).(24)(25)
In clinical trials, these drugs have been reported to reduce HbA1c by 0.5% to
1.5% depending on the dose and patient. This is in contrast to other treatments,
such as dipeptidyl peptidase-4 inhibitors (DPP-4i), which generally achieve
smaller reductions, typically in the range of 0.5% to 0.8% (26).
Considering that metformin is the rst-line treatment for type 2 diabetes
and can reduce HbA1c by 1% to 2%. However, its use may be limited in patients
with impaired renal function; ISGLT2s can be used as an adjunctive therapy,
providing additional benets in terms of weight loss and blood pressure
reduction (25,26).
DPP-4i, like sitagliptin, provide similar reductions in HbA1c (approximately
0.5% to 0.8%), but do not provide the signicant cardiovascular benets seen
with SGLT2i. A comparative study showed that patients treated with SGLT2i
had a 15% lower risk of adverse cardiovascular events compared with those
treated with DPP-4i (27).
SGLT2i are not only effective for glycemic control, but have also been
shown to reduce the risk of hospitalization for heart failure and improve renal
outcomes. Studies such as EMPA-REG OUTCOME have shown a 38% reduction
in the risk of hospitalization for heart failure and a signicant reduction in the
progression of diabetic nephropathy. These benets are particularly important
for patients with T2DM who have cardiovascular comorbidity (28).
Various studies are being carried out with ISGLT2 in which an attempt
is being made to nd the benet that exists in the reduction of cardiovascular
events in patients who have heart failure, regardless of whether they suffer
from type 2 diabetes mellitus. Currently, the only studies that are in phase 3 are
the combination of dapagliozin plus pioglitazone in patients who have heart
failure with a preserved ejection fraction (29).
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) play a dual role in
type 2 diabetes mellitus, as they can contribute to both renal damage and renal
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Sodium glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of
type 2 diabetes mellitus: Literature review 65 - 71
protection. SGLT2i can cause a modest and rapid decrease in GFR (between 3%
and 10% ) at the start of treatment. This reduction is usually temporary and
stabilizes thereafter. However, SGLT2i have been shown to reduce albuminuria
levels, suggesting a benet in preserving renal function in the long term. This is
critical to delay the progression of diabetic nephropathy (23,25).
Table 2. General comparison of antidiabetics mainly used in type 2 diabetes mellitus
(24,27,31,32)(30)(31)
Treatment Average reduction
in HbA1c
Cardiovascular
benets Common side effects
iSGLT2 0.5% - 1.5%
Reduction of major
cardiovascular
events
Genital infections,
polyuria, dizziness, diabetic
ketoacidosis, acute renal
failure.
Metformin 1% - 2% Moderate
Gastrointestinal
discomfort, lactic acidosis,
hypoglycemia, taste
disturbance, weight loss.
iDPP-4 0.5% - 0.8% Limited
Pancreatitis, respiratory
infections, nausea , diarrhea,
vitamin B12 deciency
anemia.
Sulfonylureas/Insulin Up to 2% Increased
cardiovascular risk
Hypoglycemia, nausea, skin
rashes, allergic reactions,
weight gain
Prepared by: authors of the work.
5. Conclusions
Diabetes mellitus is a chronic, non-communicable disease with increasing
prevalence and incidence worldwide, which poses serious public health
problems due to its high associated morbidity and mortality. The complications
of this disease not only affect the quality of life of patients, but also create a
signicant burden on health care systems. Therefore, it is essential to deepen
our knowledge of this pathology, as well as the therapeutic options available for
its effective management.
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DOI: https://doi.org/10.58995/redlic.rmic.v3.n1.a84
Sodium glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of
type 2 diabetes mellitus: Literature review 66 - 71
In this context, sodium cotransporter inhibitors (ISGLT2) have gained
importance in the treatment of diabetes mellitus 2. These drugs are distinguished
by their ability to reduce HbA1c levels by 0.5% to 1.5%, which translates into
more effective blood glucose control. However, their positive impact goes
beyond glycemic control, as ISGLT2 has also been shown to provide signicant
renal and cardiovascular benets.
Recent studies have shown that these drugs not only reduce the risk of
adverse cardiovascular events, but also protect kidney function, which is
essential for the long-term well-being of patients with diabetes.
A comprehensive approach to diabetes mellitus management, including
the use of ISGLT2, represents an important advance in the effort to improve the
quality of life of patients and reduce the burden of this disease in the population.
It is essential that healthcare professionals and patients are informed about
these innovative treatments, as well as the importance of rigorous diabetes
control to minimize its complications and improve long-term health outcomes.
6. Contribución de los autores
BAOT: Analysis of results, review of the article.
AFGM: Analysis of results, review of the article
EGCO: Analysis of results, review of the article
PJFB: Analysis of results, review of the article
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Sodium glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of
type 2 diabetes mellitus: Literature review 67 - 71
Referencias
1 Russo MP, Grande-Ratti MF, Burgos MA, Molaro AA, Bonella MB.
Prevalence of diabetes, epidemiological characteristics and vascular
complications. Archivos de Cardiología de México. 2023;93(1):30-6.
Retrieved from: https://acortar.link/3gn7wx
2 Cedeño J, Chancay J, Cevallos W, Castro Y. Diabetes Mellitus latent
morbidity in society: Prevalence, risk factors, sociodemographics and
clinical diagnoses. 2023;8(1). Retrieved from: https://acortar.link/
IQ2fa3
3 Gomezcoello V, Caza M, Jácome E. Prevalence of diabetes mellitus and
its complications in older adults in a referral center. Rev Med Vozandes.
2020;31(2):49-55. Retrieved from: https://acortar.link/1Tyfy8
4 Lytvyn Y, Bjornstad P, van Raalte DH, Heerspink HL, Cherney DZI.
The New Biology of Diabetic Kidney Disease—Mechanisms and
Therapeutic Implications. Endocrine Reviews. 2020;41(2):202-31.
https://acortar.link/ecN89x
5 Neary SL, Ottmann A. Diagnostic Approach to Differentiating Diabetes
Types. Vol. 5, Physician Assistant Clinics. Elsevier Inc; 2020. p. 109-20.
6 Arneth B, Arneth R, Shams M. Metabolomics of Type 1 and Type 2
Diabetes. International journal of molecular sciences. 2019;20(10):1-
14. Recovered from: : https://acortar.link/kjKE3c
7 Forouhi NG, Wareham NJ. Epidemiology of diabetes. Medicine.
2019;47(1):22-7. Recovered from: https://acortar.link/hCf178
8 Garofalo C, Borrelli S, Liberti ME, Andreucci M, Conte G, Minutolo
R, et al. SGLT2 Inhibitors: Nephroprotective Efcacy and Side
Effects. Medicine. 2019;55(6):268. Recovered from: https://acortar.
link/1eszK0
9 Nespoux J, Vallon V. SGLT2 inhibition and kidney protection. Vol. 132,
Clinical Science. Portland Press Ltd; 2018. p. 1329-39. Recovered from:
https://acortar.link/Blwztz
10 Aylwin H. CG. New drugs in diabetes mellitus. Revista Médica Clínica
Las Condes. 2016;27(2):235-56. Retrieved from: https://acortar.
link/447g9F
Revista multidisciplinaria
Investigación Contemporánea 01 - 2025 Vol. 3 - No. 1 ISSN-e: 2960-8015
DOI: https://doi.org/10.58995/redlic.rmic.v3.n1.a84
Sodium glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of
type 2 diabetes mellitus: Literature review 68 - 71
11 Ferrannini E. Sodium-Glucose Co-transporters and Their Inhibition:
Clinical Physiology. Vol. 26, Cell Metabolism. Cell Press; 2017. p. 27-
38. Recovered from: https://acortar.link/bhqfD2
12 Buitrago Sandoval AF, Sánchez Vallejo CA. Mechanisms of action of
sodium-glucose cotransporter type 2 —SGLT2— inhibitors: Beyond
glycemic control. Colombian Journal of Cardiology. 2020;27:22-5.
Retrieved from: https://acortar.link/SuD4Cd
13 Romera I, Ampudia-Blasco FJ, Pérez A, Ariño B, Pfarr E, Giljanovic Kis
S, et al. Efcacy and safety of empagliozin in combination with other
oral hypoglycemic agents in patients with type 2 diabetes mellitus.
Endocrinol Nutr. 2016; 63(10):519-26. Retrieved from: https://acortar.
link/Pca9wj
14 García Rojas ZA, Cristancho Sierra DM, Peréz Papadópulos AV,
Ormaechea Gorricho G, García Rojas ZA, Cristancho Sierra DM, et
al. Use of empagliozin in type 2 diabetic patients with heart failure.
Uruguayan Journal of Internal Medicine. 2022;7(2):37-45. Retrieved
from: https://acortar.link/iIzsYP
15 Shrikrishnapalasuriyar N, Shaikh A, Ruslan AM, Sharaf G, Udiawar
M, Price DE, et al. Dapagliozin is associated with improved glycemic
control and weight reduction at 44 months of follow-up in a secondary
care diabetes clinic in the UK. Diabetes & Metabolic Syndrome:
Clinical R earch & Reviews. 2020;14(3):237-9. Recovered from: https://
acortar.link/lLe6bt
16 Hidalgo Santiago JC, Maraver Delgado J, Cayón Blanco M, López
Saez JB, Gómez-Fernández P. Effect of dapagliozin on arterial
stiffness in patients with type 2 diabetes mellitus. Med Clin (Barc).
2020;154(5):171-4. Retrieved from: https://acortar.link/RkpHvO
17 Escudero Vilaplana B, Almodóvar Carretón MJ, Herrero Hernández
S. Dapagliozin, a novel oral antidiabetic drug with an uncertain
future. Hospital Pharmacy. 2014;38(6):468-74. Retrieved from::
https://acortar.link/m7DRHa
18 Brito M, Payares C. Therapeutic positioning report of canagliozin
(Invokana®) in type 2 diabetes mellitus. Spain: Ministry of Health,
Social Services and Equality; 2017.
Revista multidisciplinaria
Investigación Contemporánea 01 - 2025 Vol. 3 - No. 1 ISSN-e: 2960-8015
DOI: https://doi.org/10.58995/redlic.rmic.v3.n1.a84
Sodium glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of
type 2 diabetes mellitus: Literature review 69 - 71
19 López M. Sodium-glucose cotransporter 2 (SGLT2) inhibitors: the
kidney as a target for glycemic control in type 2 diabetes mellitus.
Med Int Mex. 2017;33(3):363-71. Retrieved from: : https://acortar.link/
W6qLW0
20 Mehta R, Almeda P, Yamamoto J. Current role of empagliozin in
glycemic control in patients with type 2 diabetes: from preclinical
research to phase III studies. Med Int Mex. 2015;31:301-9. Retrieved
from: https://acortar.link/acnd30
21 Utsunomiya K, Senda M, Kakiuchi S, Kameda H, Tamura M, Kurihara
Y, et al. Safety and efcacy of tofogliozin in Japanese patients with
type 2 diabetes mellitus in real-world clinical practice: Results of
3-month interim analysis of a long-term post-marketing surveillance
study (J-STEP/LT). Journal of Diabetes Investigation. 2019;10(5):1272-
83. Recovered from: https://acortar.link/tJ2irP
22 Sakai S, Kaku K, Yutaka S, Inagaki N. Efcacy and Safety of the SGLT2
Inhibitor Luseogliozin in Japanese Patients With Type 2 Diabetes
Mellitus Stratied According to Baseline Body Mass Index: Pooled
Analysis of Data From 52-Week Phase III Trials. Clinical Therapeutics.
2016;38(4). Recovered from: https://acortar.link/ZSL4U3
23 Garnica-Cuéllar JC, Lavalle-González FJ, Magaña-Serrano JA,
Almeda-Valdés P, Cetina-Canto JA, Chávez Iñíguez JS, et al. Consensus
document on the use of SGLT2 inhibitors in the treatment of patients
with type 2 diabetes mellitus. Gac Méd Méx. 2022;158(SPE1):1-14.
Retrieved from https://acortar.link/leFw6m
24 Hernández Rodríguez J. Adverse reactions of sodium-glucose
cotransporter type 2 inhibitors in people with diabetes mellitus.
Rev Cuban de Med [Internet]. 2022 [cited October 1, 2024];61(4).
Available at: http://scielo.sld.cu/scielo.php?script=sci_
abstract&pid=S0034-75232022000400002&lng=es&nrm=iso&tlng=
es
25 Morales-Olvera D, Obregón-Aguilar A, Pérez-Mendoza MT, Zanabria-
Giles P, Fanghänel-Salmón G, Sánchez-Reyes L, et al. SGLT2 inhibitors
and their potential nephroprotective effect in patients with type 2
diabetes mellitus. Med Interna Mex. 2017;33(4):503-10. Retrieved
from: https://acortar.link/bhIAaQ
Revista multidisciplinaria
Investigación Contemporánea 01 - 2025 Vol. 3 - No. 1 ISSN-e: 2960-8015
DOI: https://doi.org/10.58995/redlic.rmic.v3.n1.a84
Sodium glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of
type 2 diabetes mellitus: Literature review 70 - 71
26 Palanca A. SGLT2 inhibitors: New therapeutic option in type 1
diabetes? [Internet]. Diabetes; 2022 [cited October 1, 2024]. Available
at: https://www.revistadiabetes.org/?p=103762
27 D'Andrea E, Wexler D, Kim S. Comparing Effectiveness and Safety
of SGLT2 Inhibitors vs DPP-4 Inhibitors in Patients With Type 2
Diabetes and Varying Baseline HbA1c Levels. JAMA. 2023;183(2):242-
54. Recovered from: https://acortar.link/NqZSm5
28 Fu EL, Patorno E, Everett BM, Vaduganathan M, Solomon SD, Levin
R, et al. Sodium–glucose cotransporter 2 inhibitors vs. Sitagliptin
in heart failure and type 2 diabetes: an observational cohort study.
European Heart Journal. 2023;44(24):2216-30. Recovered from:
https://acortar.link/ZHU04J
29 Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et
al. Empagliozin, Cardiovascular Outcomes, and Mortality in Type
2 Diabetes. New England Journal of Medicine. 2015;373(22):2117-28.
Recovered from: https://acortar.link/uAsOfX
30 Gómez Mesa JE, Montes MC, González Juanatey JR. The future of
research and what to expect from sodium-glucose cotransporter
type 2 inhibitors —i-SGLT2—. Colombian Journal of Cardiology.
2020;27:40-4. Retrieved from: https://acortar.link/w2seWh
31 Carramiñana Barrera FC. Safety of dipeptidyl peptidase 4 inhibitors.
Semergen. 2018;44:10-7. Retrieved from: https://acortar.link/iBwztJ
32 Mata Cases M. Metformin and type 2 diabetes mellitus. Aten Primaria.
2008;40(3):147-53. Retrieved from: https://acortar.link/GLV6aw
Revista multidisciplinaria
Investigación Contemporánea 01 - 2025 Vol. 3 - No. 1 ISSN-e: 2960-8015
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Sodium glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of
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