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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a world health issue during the last months, affecting mostly countries with a high metabolic risk, like Mexico. Patients with type 2 diabetes (T2D) have an increased risk of any kind of infection as well as an increased mortality risk. Hyperglycemia has been established as an important predictor of mortality in patients with T2D and SARS-CoV-2. The standard treatment of hyperglycemia in hospitalized patients has been basen on insulin schemes, but recently evidence suggest the utility of some other drugs, reducing the risk of hypoglucemia and increasing the probability of a proper metabolic control. The goal of this study is to compare the utility of dipeptidyl peptidase-4 inhibitor (DPP4i) as a combination with insulin on metabolic control and prognosis in hospitalized patients with SARS-CoV-2 and hyperglycemia.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a world health issue during the last months, affecting mostly countries with a high metabolic risk, like Mexico. Patients with type 2 diabetes (T2D) have an increased risk of any kind of infection as well as an increased mortality risk. Hyperglycemia has been established as an important predictor of mortality in patients with T2D and SARS-CoV-2. The standard treatment of hyperglycemia in hospitalized patients has been basen on insulin schemes, but recently evidence suggest the utility of some other drugs, reducing the risk of hypoglucemia and increasing the probability of a proper metabolic control. DPP4 enzyme has an ubiquitous distribution and has been considered as a pro-inflammatory enzyme, considering that DPP4 inhibitors could have and anti-inflammatory effect, as it has been shown in different works. The goal os this study is to compare the utility of DPP4 inhibitor as a combination with insulin on metabolic control and prognosis in hospitalized patients with SARS-CoV-2 and hyperglycemia. For this purpose we will randomize patients with SARS-CoV-2 and hyperglycemia to receive either the combination of DPP4i + insulin or insulin alone and will follow al algorithm treatment to define metabolic control as well as prognosis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DPP4 inhibitor + insulin | Experimental | Patients assigned to this group of treatment will receive Linagliptin 5mg orally once daily plus a basal-bolo insulin scheme |
|
| Insulin scheme alone | Active Comparator | Patients assigned to this group will receive only a basal-bolus insulin scheme |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Linagliptin tablet | Drug | Linagliptin 5mg once daily plus a basal-bolus insulin scheme |
|
| Measure | Description | Time Frame |
|---|---|---|
| Glucose levels | Glucose levels during hospitalization | 5-10 days |
| Number of patients who achieve metabolic control | Patients who achieve fasting glucose levels below 140 mg/dl and posprandial levels below 180 mg/dl | 5-10 days |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients who die or need mechanical ventilation | If the patient requires mechanical ventilation or dies | 5-10 days |
| C reactive protein levels | C reactive protein measured at basal and at 5-10 days in mg/dl |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rodolfo Guardado, PhD | Hospital Regional de Alta Especialidad del Bajìo | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Regional de Alta Especialidad del Bajìo | Leòn | Guanajuato | 37660 | Mexico |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15308380 | Background | DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am. 2004 Jul;88(4):787-835, ix. doi: 10.1016/j.mcna.2004.04.013. | |
| 9539990 | Background | Levetan CS, Passaro M, Jablonski K, Kass M, Ratner RE. Unrecognized diabetes among hospitalized patients. Diabetes Care. 1998 Feb;21(2):246-9. doi: 10.2337/diacare.21.2.246. |
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Sharing of the data can be done, depending on the requested purposes
Data will be available once the main results of the study are published, and in accordance with the journal
Direct contact with the principal investigator
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 1, 2020 | Sep 4, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006943 | Hyperglycemia |
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D011024 | Pneumonia, Viral |
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| ID | Term |
|---|---|
| D000069476 | Linagliptin |
| D007328 | Insulin |
| ID | Term |
|---|---|
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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The study will include two parallel groups of intervention
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Physicians who will be providing health support will not be aware of the treatment that patients will be receiving regarding this protocol, also the principal investigator and the personal who will be measuring glucose levels and prognosis, will not be aware of the group of treatment, since all the patients will be receiving the same protocol of insulin administration
| Insulin | Drug | Basal-bolus insulin scheme |
|
|
| 5-10 days |
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| 31350829 | Background | Soare A, Gyorfi HA, Matei AE, Dees C, Rauber S, Wohlfahrt T, Chen CW, Ludolph I, Horch RE, Bauerle T, von Horsten S, Mihai C, Distler O, Ramming A, Schett G, Distler JHW. Dipeptidylpeptidase 4 as a Marker of Activated Fibroblasts and a Potential Target for the Treatment of Fibrosis in Systemic Sclerosis. Arthritis Rheumatol. 2020 Jan;72(1):137-149. doi: 10.1002/art.41058. |
| 31010001 | Background | Beraldo JI, Benetti A, Borges-Junior FA, Arruda-Junior DF, Martins FL, Jensen L, Dariolli R, Shimizu MH, Seguro AC, Luchi WM, Girardi ACC. Cardioprotection Conferred by Sitagliptin Is Associated with Reduced Cardiac Angiotensin II/Angiotensin-(1-7) Balance in Experimental Chronic Kidney Disease. Int J Mol Sci. 2019 Apr 20;20(8):1940. doi: 10.3390/ijms20081940. |
| 28251104 | Background | Kagal UA, Angadi NB, Matule SM. Effect of dipeptidyl peptidase 4 inhibitors on acute and subacute models of inflammation in male Wistar rats: An experimental study. Int J Appl Basic Med Res. 2017 Jan-Mar;7(1):26-31. doi: 10.4103/2229-516X.198516. |
| 32463179 | Background | Fadini GP, Morieri ML, Longato E, Bonora BM, Pinelli S, Selmin E, Voltan G, Falaguasta D, Tresso S, Costantini G, Sparacino G, Di Camillo B, Tramontan L, Cattelan AM, Vianello A, Fioretto P, Vettor R, Avogaro A. Exposure to dipeptidyl-peptidase-4 inhibitors and COVID-19 among people with type 2 diabetes: A case-control study. Diabetes Obes Metab. 2020 Oct;22(10):1946-1950. doi: 10.1111/dom.14097. Epub 2020 Jul 1. |
| 27964837 | Background | Pasquel FJ, Gianchandani R, Rubin DJ, Dungan KM, Anzola I, Gomez PC, Peng L, Hodish I, Bodnar T, Wesorick D, Balakrishnan V, Osei K, Umpierrez GE. Efficacy of sitagliptin for the hospital management of general medicine and surgery patients with type 2 diabetes (Sita-Hospital): a multicentre, prospective, open-label, non-inferiority randomised trial. Lancet Diabetes Endocrinol. 2017 Feb;5(2):125-133. doi: 10.1016/S2213-8587(16)30402-8. Epub 2016 Dec 8. |
| 23877988 | Background | Umpierrez GE, Gianchandani R, Smiley D, Jacobs S, Wesorick DH, Newton C, Farrokhi F, Peng L, Reyes D, Lathkar-Pradhan S, Pasquel F. Safety and efficacy of sitagliptin therapy for the inpatient management of general medicine and surgery patients with type 2 diabetes: a pilot, randomized, controlled study. Diabetes Care. 2013 Nov;36(11):3430-5. doi: 10.2337/dc13-0277. Epub 2013 Jul 22. |
| 35017617 | Derived | Guardado-Mendoza R, Garcia-Magana MA, Martinez-Navarro LJ, Macias-Cervantes HE, Aguilar-Guerrero R, Suarez-Perez EL, Aguilar-Garcia A. Effect of linagliptin plus insulin in comparison to insulin alone on metabolic control and prognosis in hospitalized patients with SARS-CoV-2 infection. Sci Rep. 2022 Jan 11;12(1):536. doi: 10.1038/s41598-021-04511-1. |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D011799 | Quinazolines |
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |