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Available online 5 December 2021
Incretin-based therapy for glycemic control of hospitalized patients with type 2 diabetes: a systematic review
Terapia basada en incretinas para control glucémico de los pacientes hospitalizados con diabetes tipo 2: una revisión sistemática
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A.E. Gracia-Ramosa,b,
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dr.gracia.dmm@gmail.com

Corresponding author.
, M.P. Cruz-Domínguezc, E.O. Madrigal-Santillánd
a Departamento de Medicina Interna, Hospital General, Centro Médico Nacional "La Raza", Instituto Mexicano del Seguro Social, Ciudad de México, Mexico
b Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, Mexico
c División de Investigación en Salud, Hospital de Especialidades, Centro Médico Nacional "La Raza", Instituto Mexicano del Seguro Social, Ciudad de México, Mexico
d Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, Mexico
Received 22 July 2021. Accepted 02 September 2021
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Table 1. Clinical trials on incretin-based therapy in the hospital setting outside of the critical care unit.
Abstract

Incretin-based therapy leads to glycemic control in a glucose-dependent manner with a low risk of hypoglycemia, making it appealing for use in the hospital. The aim of this systematic review was to assess the benefits of incretin-based therapy in patients with type 2 diabetes hospitalized outside of the intensive care unit. We searched for studies published up to August 2021 in the PubMed and Scopus databases. Clinical trials comparing incretin-based therapy (alone or in combination with insulin) versus an insulin regimen were selected. The results of the included studies showed that incretin-based therapy showed mean blood glucose values, a percentage of records within the therapeutic target, and a percentage of treatment failure similar to insulin management, particularly in patients with mild to moderate hyperglycemia. Furthermore, incretin-based treatment was associated with a lower total insulin dose and a lower incidence of hypoglycemia. In conclusion, incretin-based therapy achieved glycemic control similar to insulin treatment in patients with type 2 diabetes hospitalized outside the intensive care unit and has the advantages of reducing the insulin requirement and a lower risk of hypoglycemia.

Keywords:
Inpatient
Diabetes
Antidiabetics
Insulin
Incretins
Resumen

La terapia basada en incretinas lleva al control glucémico de una manera dependiente de glucosa con un bajo riesgo de hipoglucemia, por lo que resulta atractiva para su uso hospitalario. El objetivo de esta revisión sistemática fue evaluar los beneficios de la terapia basada en incretinas en pacientes con diabetes tipo 2 hospitalizados fuera de la unidad de cuidados intensivos. Se buscaron estudios publicados hasta agosto de 2021 en las bases de datos PubMed y Scopus. Se seleccionaron los ensayos clínicos que comparaban la terapia basada en incretinas (sola o en combinación con insulina) versus el régimen con insulina. Los resultados de los estudios incluidos mostraron que la terapia basada en incretinas registró un promedio de glucosa sanguínea, un porcentaje de registros dentro de meta terapéutica y un porcentaje de falla al tratamiento similar al manejo con insulina, particularmente en pacientes con hiperglucemia leve a moderada. Además, el tratamiento basado en incretinas se asoció con una menor dosis total de insulina y una menor incidencia de hipoglucemia. En conclusión, la terapia basada en incretinas logró un control glucémico similar al tratamiento con insulina en los pacientes con diabetes tipo 2 hospitalizados fuera de la unidad de cuidados intensivos, con la ventaja de disminuir el requerimiento insulínico y con menor riesgo de hipoglucemia.

Palabras clave:
Paciente hospitalizado
Diabetes
Antidiabéticos
Insulina
Incretinas
Full Text
Introduction

Hyperglycemia (defined as a blood glucose concentration >140 mg/dL) in the hospital setting is a common, harmful, costly health problem.1,2 It is present in one in three hospitalized patients and has been associated with an increase in the mortality and morbidity of both medical and surgical ailments.3–7 Therefore, various professional organizations recommend providing treatment for hyperglycemia to patients hospitalized outside of an intensive care unit (ICU) through the administration of subcutaneous insulin (habitually in a basal-bolus regimen) with a therapeutic target for blood glucose of 100 to 180 mg/dL.1,8–11 However, this approach has been limited by its complexity and risk of hypoglycemia.

A Cochrane systematic review that analyzed 1048 participants in eight randomized clinical trials found that the administration of insulin in a basal-bolus regimen can result in better glucose control, but increases the risk of severe hypoglycemic episodes in patients hospitalized with type 2 diabetes mellitus (DM2).12

Various clinical practice guidelines advise against the in-hospital use of non-insulin antidiabetic agents due to a dearth of information on their safety and efficacy.1,8–10 Despite this, some of these medications are frequently used in the hospital (metformin in up to 58%, sulfonylureas in up to 29%, thiazolidinediones in up to 11% of patients).13,14 However, their use can be associated with the onset of adverse effects such as lactic acidosis (metformin), hypoglycemia (sulfonylureas), liquid retention and heart failure (thiazolidinediones), or euglycemic diabetic ketoacidosis (sodium–glucose cotransporter 2 inhibitors, SGLT-2i).15–19

On the other hand, there is great interest in the use of incretin-based therapies (glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors) to improve glycemic control in hospitalized patients with diabetes due to their mechanism of action and safety profile. The use of these agents is appealing thanks to their metabolic effects, such as the glucose-dependent stimulation of insulin secretion and inhibition of glucagon secretion, which leads to better glycemic control with low rates of hypoglycemia.20–23

Various studies have explored the in-hospital use of GLP-1 receptor agonists and DPP-4 inhibitors. The aim of this systematic review is to evaluate the benefits of incretin therapy in patients with DM2 hospitalized in non-critical care departments.

Methods

In accordance with the recommendations of the 2020 PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines,24 a research question was formulated following the PICO format: P (patients): patients with DM2 hospitalized outside of the ICU; I (intervention): incretin-based therapy; C (comparator): treatment with insulin; O (outcomes): efficacy (mean daily blood glucose, percentage of readings within the therapeutic target, percentage of treatment failure, total insulin dose) and safety (hypoglycemic episodes, adverse events).

A literature search was conducted on PubMed and Scopus for works published as of August 21, 2021 using the following MeSH (Medical Subject Headings) terms: Dipeptidyl-Peptidase IV Inhibitors, Glucagon-Like Peptide-1 Receptor, Incretins, Diabetes Mellitus, Type 2, Hyperglycemia, Inpatients, Hospitalization. Randomized clinical trials on patients with DM2 hospitalized outside of critical care departments in which the use of incretin therapy was compared to insulin treatment were included; there were no restrictions regarding language.

Any publications which did not meet the above criteria were excluded. Information on the selected studies included the following: authors and/or study name, year of publication, patients’ general characteristics, treatment groups, primary aim of the study, and outcomes established in the PICO question.

ResultsSelection of studies

A total of 1099 records were identified in the databases explored. After eliminating duplicates, the title and abstract of 872 records were reviewed and 30 articles were selected for an in-depth analysis. In the end, nine studies were included in this review (Fig. 1 and Table 1).25–33

Figure 1.

Study selection flowchart.

CT: randomized clinical trial; MeSH: Medical Subject Headings; ICU: intensive care unit.

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Table 1.

Clinical trials on incretin-based therapy in the hospital setting outside of the critical care unit.

Trial/author (year)  Treatment groups  Population  Primary outcome  Main findings 
DPP-4 inhibitors
Sita-Pilot (2013)25  - Sitagliptin (50–100 mg/day)- Sitagliptin (50-100 mg/day) + basal insulin (0.15–0.25 U/kg/day)- Basal-bolus insulin regimen (0.3–0.5 U/kg/day)  N = 90Patients with DM2 in the medical department (55) or surgical department (35); blood glucose 140–400 mg/dL; management with diet, OAD, or insulin (0.4 U/kg/day)  Difference in mean daily blood glucose level  No difference in mean daily glucose level after day 1 of treatment (168 ± 35 vs. 154 ± 29 vs. 158 ± 31 mg/dL, p = .23), length of hospital stay in days (p = 0.78), or hypoglycemic events (p = 0.78) between groups. Patients treated with sitagliptin alone and with initial glucose levels >180 mg/dL had a higher mean glucose level (p = 0.08) 
Sita-Hospital (2017)26  - Sitagliptin (50–100 mg/day) + basal insulin (0.15–0.25 U/kg/day)- Basal-bolus insulin regimen (0.3–0.5 U/kg/day)  N = 277Patients with DM2 in the medical department (233) or surgical department (44); blood glucose 140–400 mg/dL; management with diet, OAD, or insulin (≤0.6 U/kg/day).  No difference in mean daily blood glucose level  No difference in mean daily glucose (171.2 ± 48.6 vs. 169.4 ± 48.6 mg/dL, p = 0.79) or hypoglycemic episodes (9% vs. 12%, p = 0.79) between the groups. Lower dose and number of applications of insulin needed in the sitagliptin + basal insulin group 
Linagliptin-Surgery (2019)27  - Linagliptin (5 mg/day)- Basal-bolus insulin regimen (0.4–0.5 U/kg/day)  N = 280Patients with DM2 who underwent non-cardiac surgery; blood glucose 140–400 mg/dL; management with diet, OAD, or insulin (≤0.5 U/kg/day)  No difference in mean daily blood glucose level  Higher mean glucose in the linagliptin group (171.2 ± 46.8 vs. 158.5 ± 41.4 mg/dL, p = 0.03). Fewer hypoglycemic events with linagliptin (1.6% vs. 11%; p = 0.001) 
Garg et al. (2017)28  - Saxagliptin (2.5–5 mg/day)- Basal-bolus insulin regimen (0.5 U/kg/day)  N = 66Patients with DM2 in the medical department (17) or surgical department (49), HbA1c ≤7.5%, and management with ≤ 2 OAD  Mean daily blood glucose in days 2 to 5 of the study  No difference in mean daily glucose (149.8 ± 22 vs. 146.9 ± 30.5 mg/dL, p = 0.59) or incidence of hypoglycemia (0.4% vs. 0.3%) between the groups 
Lyu et al. (2020)29  - Vildagliptin (50 mg twice per day) + CSII (0.7 U/kg/day)- CSII (0.7 U/kg/day)  N = 200Patients with DM2 in the medical department, HbA1c ≥8.5%, BMI 18-28 kg/m2, management with OAD  Mean daily blood glucose during 7 days of treatment  Use of vildagliptin + CSII resulted in a lower mean daily glucose (170.4 ± 58.2 mg/dL vs. 178.2 ± 60.7 mg/dL, p < 0.01) and fewer hypoglycemic episodes (1.75% vs. 4.04%, p = 0.05) 
GLP-1 receptor agonists
Polderman et al. (2018)30  - Liraglutide (0.6 mg SC, 1.2 mg SC on the morning of the surgery)- Glucose-insulin-potassium infusion- Bolus insulin regimen (50% of what is used at home)  N = 150Patients with DM2 scheduled for non-cardiac surgery; management with diet, OAD, or insulin <1 U/kg  Difference in mean glucose at post-operative hour 1  The mean glucose at hour 1 following surgery was lower in the liraglutide group (118.9 vs. 138.7 vs. 135.1 mg/dL, p = 0.006). There were no differences in onset of hypoglycemia (p = 0.26). Greater incidence of nausea with the use of liraglutide (p = 0.007) 
Kaneko et al. (2018)31  - Liraglutide (0.6-1.2 mg SC)- Basal insulin therapy  N = 90Patients with DM2 scheduled for elective surgery, management with OAD, BMI > 20, HbA1c ≥6%  Perioperative glucose control  The mean postprandial glucose the day before surgery and the day of surgery was lower with the use of liraglutide (156.0 ± 13.3 vs. 194.6 ± 15.4 mg/dL, p = 0.004; 167.6 ± 13.6 vs. 221 ± 5.4 mg/dL, p < 0.001). Those treated with liraglutide did not present with hypoglycemia but 6.1% presented with nausea 
Fayfman et al. (2019)32  - Exenatide (5 μg/twice per day)- Exenatide (5 μg/twice per day) + basal insulin (0.15–0.25 U/kg/day)- Basal-bolus insulin regimen (0.3–0.5 U/kg/day)  N = 150Patients with DM2 in the medical department (106) or surgical department (44); blood glucose 140-400 mg/dL; management with diet, OAD, or insulin (0.5 U/kg/day)  Difference in mean daily blood glucose during the hospital stay  The mean daily blood glucose of the exenatide + basal insulin group was similar to that of the basal-bolus insulin group (154 ± 6.39 vs. 166 ± 6.40 mg/dL, p = .31) and lower than that of the group receiving exenatide alone 177 ± 6.41 mg/dL, p = 0.02). The incidence of nausea and vomiting was higher in the exenatide groups (10% vs. 11% vs. 2%; p = .17) 
Fushimi et al. (2020)33  - Dulaglutide (0.75 mg SC) + basal insulin (0.15–0.25 U/kg/day)- Basal insulin (0.15–0.25 U/kg/day)  N = 54Patients with DM2 in the medical or surgical department; glucose <400 mg/dL; management with diet, OAD, or insulin (<10 U/day)  Percentage of blood glucose measurements in a range of 100–180 mg/dL  The percentage that reached the primary outcome was higher (56% vs. 44%, p < 0.001) and the frequency of blood glucose >240 mg/dL or <70 mg/dL was lower in the dulaglutide + basal insulin group (both p < 0.001) 

BMI: body mass index; CSII: continuous subcutaneous insulin infusion; DM2: type 2 diabetes mellitus; DPP-4: dipeptidyl peptidase-4; GLP-1: glucagon-like peptide-1; HbA1c: glycosylated hemoglobin; OAD: oral antidiabetics; SC: subcutaneous.

Characteristics of studies included

The studies included a total of 1361 patients, of which 464 received treatment with a DPP-4 inhibitor and 220 with a GLP-1 receptor agonist. The DPP-4 inhibitors were sitagliptin (2), linagliptin (1), saxagliptin (1), and vildagliptin (1),25–29 The GLP-1 receptor agonists were liraglutide (2), exenatide (1), and dulaglutide (1).30–33 In five studies, incretin therapy was used in combination with insulin.25,26,29,32,33 The comparator treatment was insulin administered in the following manner: basal-bolus regimen (five trials),25–28,32 basal insulin (two trials),31,33 and continuous insulin infusion and intravenous insulin boli (one trial each).29,30

In general, the patients included were of both sexes; had a known DM2 diagnosis; were treated with diet, oral antidiabetics, or insulin (total daily dose ≤0.6 U/kg); and had a blood glucose level prior to randomization of between 140 and 400 mg/dL. One study only included patients treated with ≤2 antidiabetics or with glycosylated hemoglobin (HbA1c) ≤7.5%28 whereas another trial only included individuals with an HbA1c ≥8.5%.29

The patients came from both medical and surgical departments in five studies,25,26,28,32,33 only a surgical department in three studies,27,30,31 and only a medical department in one study.29

Efficacy of incretin-based therapy

In general, incretin-based treatment resulted in a rapid, sustained improvement in glycemic control during the hospital stay. The mean daily blood glucose level with incretin-based therapy (alone or in combination with insulin) was reported to be between 149.8 mg/dL and 171.2 mg/dL, similar to what was observed with an insulin regimen (146.9–169.4 mg/dL).25,26,28,32

In four studies, the group treated with incretins showed a better mean blood glucose level: (170.4 vs. 178.2 mg/dL (p < 0.01) in the study by Lyu et al.,29 118.9 vs. 138.7 mg/dL (p = 0.006) in the study by Polderman et al.,30 156 vs. 194.6 mg/dL (p < 0.001) in the study by Kaneko et al.,31 and 162 vs. 183 mg/dL (p < 0.05) in the study by Fushimi et al.).33 However, in three studies in which incretin therapy was administered without combined insulin, the mean glucose level was higher compared to the use of insulin (168.4 vs. 158.3 mg/dL in the study by Umpierrez et al.,25 171.2 vs. 158.5 mg/dL in the study by Vellanki et al.,27 and 177 vs. 166 mg/dL in the study by Fayfman et al.32). A subanalysis of the study by Vellanki et al. showed that the mean glucose level was similar between the groups in patients with a glucose level <200 mg/dL at the time of their randomization (p = 0.43).27

In four studies, there were no differences between groups in the number of readings within a therapeutic target of 70 to 180 mg/dL (57%-78% for those treated with incretins vs. 59.6%-66% for those treated with insulin).25–28,32 Garg et al.28 reported a similar percentage in the treatment groups (42% vs. 37%, p = 0.16), but the therapeutic target established was 70-140 mg/dL. In the study by Lyu et al., the therapeutic target was achieved by a higher proportion of those treated with vildagliptin plus insulin infusion (62.96% vs. 57.1%, p < 0.01).29 Fushimi et al. also reported that the therapeutic target was achieved in a greater proportion with dulaglutide plus basal insulin (56% vs. 44%, p < 0.001); however, the predefined target was 100-180 mg/dL.33 On the other hand, Fayfman et al. reported that the therapeutic target was achieved in a lower proportion in the arm treated with exenatide alone (62.3%).32 Two studies did not report this outcome.30,31

Treatment failure (defined as a mean blood glucose level >240 mg/dL, with the exception of the study by Garg et al.,28 in which it was defined as a level >200 mg/dL) was reported in five studies. In them, there were no differences between those who received incretin-based therapy and those treated with an insulin regimen (0%-17% vs. 0%-19%).25–28,32 In four studies, this outcome was not recorded. However, Fushimi et al.33 reported that the percentage of blood glucose readings >240 mg/dL was lower with the use of dulaglutide plus insulin (8% vs. 21%, p < 0.001) whereas Lyu et al.29 reported that the percentage of readings >180 mg/dL was lower among those who received vildagliptin plus insulin (37.04% vs. 42.9%; p < 0.01) and Polderman et al. reported that it was similar among the groups studied (36% vs. 34% vs. 45%, respectively, p = 0.456).30

In general, the total insulin dose was greater in the groups treated with insulin regimens than in those on incretin therapy. The range of insulin doses used was between 13.3 U/day and 39.8 U/day for those on an insulin regimen and between 2.4 U/day and 29.1 U/day for those who received incretin-based therapy.25–32 However, in the study by Fushimi et al.33, there were no differences between groups in the total insulin dose (17.1 vs. 16.1 U/day; p = 0.762).

Safety of incretin-based therapy

With incretin-based therapy, a percentage of hypoglycemia (defined as a blood glucose level <70 mg/dL) of between 0% and 11% was reported whereas treatment with an insulin regimen yielded a percentage of between 1% and 33%.25–33 In three studies, the percentage of hypoglycemia was significantly lower.27,29,31

In regard to adverse events associated with incretin treatment, use of DPP-4 inhibitors led to one case of cerebral infarction in the study by Pasquel et al.26 and one case of nausea and one case of urinary retention in the study by Vellanki et al.27 No study reported episodes of acute heart failure or decompensation of pre-existing heart failure.

On the other hand, in the studies that used GLP-1 receptor agonists, gastrointestinal symptoms were recorded in 6% to 41% of patients;30–33 however, only one study reported the withdrawal of three patients due to intolerance of these symptoms.32 No other type of adverse events were recorded with this group of medications.

Discussion

Based on the evidence derived from the clinical trials analyzed in this systematic review, the use of incretin-based therapy alone or in combination with insulin has been demonstrated to improve mean daily blood glucose levels and the percentage of readings within the therapeutic target in a manner similar to insulin therapy, particularly in patients with mild to moderate hyperglycemia. Furthermore, incretin-based treatment was associated with a lower total insulin dose and a lower incidence of hypoglycemia.

Control of in-hospital hyperglycemia has been shown to reduce mortality and the onset of complications such as renal failure or infections in both critical patients and those on the general ward.34–36 Management of in-hospital hyperglycemia is based on the administration of insulin, as the use of other antidiabetics is advised against due to a dearth of prospective studies.1,8–11 However, in recent years, incretin-based therapies have been used in various clinical trials that have been analyzed in this systematic review. It has been found that these medications lead to a mean blood glucose of <180 mg/dL and up to two-thirds of readings being within the therapeutic target. Such findings are similar to those found in clinical trials that analyze in-hospital insulin regimens. Said studies report a mean blood glucose of 155 mg/dL to 163 mg/dL with the use of analog or human insulin in both a basal-bolus or basal-plus regimen.37–39

A recent clinical trial by Pasquel et al. which analyzed the use of insulin glargine 100 U compared to insulin 300 U (both in a basal-bolus regimen) for treating hospitalized patients with DM2 found that both groups had a mean blood glucose >180 mg/dL.40

In a systematic review that evaluated the use of insulin in a basal-bolus regimen in five clinical trials and seven observational studies, the range of glucose readings within the therapeutic target was 34% to 66%.41

Although the proportion of treatment failure was similar among the arms of the different trials included, three studies reported a higher mean glucose level when incretin-based therapy without basal insulin was used.25,27,32 In the study by Garg et al.,28 there were no differences in mean glucose levels with the use of saxagliptin alone compared to a basal-bolus insulin regimen, although the patients enrolled had an HbA1c ≤7.5%.

The study by Pasquel et al.26 reported that the risk of treatment failure was associated with elevated HbA1c values. In a post-hoc analysis that included three clinical trials in which a DPP-4 inhibitor was used for in-hospital management of patients with DM2, a blood glucose concentration >200 mg/dL prior to randomization was associated with a higher mean glucose level during the treatment, lower compliance with the therapeutic target, and a greater percentage of treatment failure.42 Therefore, it is possible that incretin therapy should be considered preferential for the management of patients with mild to moderate hyperglycemia.

In the studies included in this systematic review, incretin-based therapy led to a significant reduction in the total insulin dose to less than 30 U/day. In clinical trials and observational studies that included a basal-bolus insulin regimen, the total daily insulin dose was up to 55.6 U/day.41 Therefore, use of a lower insulin dose to achieve glycemic control is an example of the efficacy of incretin-based treatment.

The incidence of hypoglycemia in patients hospitalized with DM2 treated with an insulin regimen varied widely, ranging from 3% to 62.9%.43–45 With incretin-based therapy, the percentage of hypoglycemia did not exceed 11%. Minimizing the frequency of hypoglycemic events is of great importance among hospitalized patients, given that its presence is associated with cardiovascular events, increased mortality, and increased length of hospital stay.46

In regard to potential adverse effects of incretin-based therapy, no episodes of pancreatitis or heart failure were reported with the use of DPP-4 inhibitors. However, outpatient management with saxagliptin and alogliptin has been linked to an increase in hospitalizations due to heart failure and thus, the in-hospital use of these formulations should be avoided in patients with pre-existing cardiopathy until there is more evidence on their cardiovascular safety.47

On the other hand, the percentage of patients with gastrointestinal symptoms with GLP-1 receptor analogs was shown to range from 6% to 41%, although only three patients withdrew from the clinical trial due to intolerance of these symptoms.30–33 More evidence is required in order to establish whether the frequency of gastrointestinal manifestations is similar to what is found in the outpatient setting (10% to 25%).48

This review has some limitations, such as heterogeneity among the studies included and the limited number of clinical trials, some of which had a small number of patients (pilot studies). However, pilot studies are important given that they can provide reliable evidence on new interventions that allow for new, large-scale clinical trials.49

Conclusion

The findings of this systematic review indicate that incretin-based therapy either alone or in combination with insulin leads to a glycemic control similar to insulin treatment in patients with DM2 hospitalized outside of the ICU, particularly in those with mild to moderate hyperglycemia. In addition, it has the advantage of requiring a lower dose of insulin and a low incidence of hypoglycemia. Therefore, we propose a treatment algorithm in order to facilitate the use of this group of medications in clinical practice (Fig. 2).

Figure 2.

Proposed algorithm for the management of hyperglycemia in patients hospitalized with type 2 diabetes mellitus.

1The choice of regimen is based on patients’ individual characteristics: (i) consider a dipeptidyl peptidase-5 (DPP-4) inhibitor, a glucagon-like peptide-1 (GLP-1) receptor agonist, or a basal-plus insulin regimen according to the following: blood glucose between 180 and 240 mg/dL, glycosylated hemoglobin (HbA1c) <9% without prior use of insulin or use at a dose of ≤0.5 U/kg/day, patient who is fasting or with poor food intake, elderly patients or those with kidney failure; (ii) prioritize a basal-bolus insulin regimen in the following scenarios: blood glucose >240 mg/dL, previous insulin therapy at a dose >0.5 U/kg/day, or HbA1c ≥9%.

2Consider incretin-based therapy with the following formulations: (i) DPP-4 inhibitors: (50–100 mg/day), linagliptin (5 mg/day), saxagliptin (2.5–5 mg/day), vildagliptin (50 mg/twice per day); (ii) GLP-1 receptor agonists: liraglutide (0.6–1.2 mg SC/day), exenatide (5 μg/SC/twice per day), dulaglutide (0.75 mg SC/week).

3Incretin therapy can be given alone or in combination with basal insulin (long-acting insulin at a dose of 0.15–0.25 U/kg/day).

4Use a dose of 0.15 U/kg/day in patients >70 years or those with a glomerular filtration rate <30 mL/min/1.73 m2.

(0.36MB).
Funding

The authors declare that they have not received any type of funding for the creation of this article.

Conflicts of interest

The authors declare that they do not have any conflicts of interest.

Acknowledgments

The authors would like to extend their gratitude to the anonymous reviewers of this manuscript for their comments and suggestions, which helped improve its content. We would also like to thank the Sección de Estudios de Posgrado e Investigación of the Escuela Superior de Medicina del Instituto Politécnico Nacional for the support provided during the process of creating this article.

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Please cite this article as: Gracia-Ramos AE, Cruz-Domínguez MP, Madrigal-Santillán EO. Terapia basada en incretinas para control glucémico de los pacientes hospitalizados con diabetes tipo 2: una revisión sistemática. Rev Clin Esp. 2021. https://doi.org/10.1016/j.rce.2021.09.002

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