SITAgliptin Plus GLARgine to Glycemic Control in the Hospital Setting (SITAGLAR-H)

NCT05579119 | Completed Phase 4

• 1 other identifier: R-2021-3501-078
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

In noncritically hospitalized patients, hyperglycemia (defined as blood glucose \[BG\] levels \>140 mg/dL) is a common, serious, and costly healthcare problem. On the other hand, the treatment of hyperglycemia is associated with decreased mortality and morbidity. Therefore, clinical guidelines from professional organizations recommend using subcutaneous insulin as the preferred therapy in hospitalized patients in a non-intensive care unit setting (target glucose range 100 - 180 mg/dl). The most recommended regimen is basal-bolus insulin therapy, although this regimen requires multiple daily insulin injections and is associated with a significant risk of hypoglycemia (reported in up to 32%). Thus, a more straightforward regimen that results in similar glycemic efficacy to basal-bolus insulin with less risk of hypoglycemia could improve care for this group of patients. The basal-plus insulin regimen consists of a daily dose of basal insulin with supplemental (corrective) doses of rapid-acting insulin analogue before meals. This has similar efficacy and safety as the basal-bolus regimen. However, the basal-plus scheme does not provide prandial coverage of insulin. In another vein, dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of oral glucose-lowering agents that reduce the breakdown of endogenous glucagon-like peptide-1 (GLP-1), stimulating insulin secretion in a glucose-dependent manner. Some clinical trials have demonstrated that DPP-4 inhibitors, in combination with insulin, result in similar improvement in glycemic control and lower rates of hypoglycemia compared to basal-bolus insulin regimens. For the above, using a long-acting insulin analogue with a DPP-4 inhibitor could provide better glycemic control basal and prandial, and this scheme could represent an alternative to using a basal-plus regimen alone. In the present study, the investigators will conduct a prospective randomized clinical trial (RCT) to compare the DPP-4 inhibitor, sitagliptin, combined with basal-plus insulin therapy and basal-plus insulin scheme alone in non-critical hospitalized patients.

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Change of the mean daily blood glucose levels during hospital

  Change of the mean daily blood glucose during the hospitalization between the groups

  During hospitalization

Secondary Outcomes (5)

• Percentage of blood glucose readings in 100-180 mg/dL range

  During hospitalization, up to 10 days

• Dose of Insulin

  During hospitalization, up to 10 days

• Incidence of hypoglycemia (BG <70 mg/dL)

  During hospitalization, up to 10 days

• Percentage of blood glucose reading >180 mg/dL

  During hospitalization, up to 10 days

• Mean length of stay in days in the hospital among different groups

  During hospitalization, up to 10 days

Study Arms (2)

Sitagliptin + glargine

EXPERIMENTAL

Sitagliptin and glargine once daily + correction doses of lispro if needed.

Drug: Sitagliptin 100mg; Drug: Glargine; Drug: Lispro

Basal-plus

ACTIVE COMPARATOR

Glargine once daily plus correction doses of lispro if needed.

Drug: Glargine; Drug: Lispro

Interventions

Sitagliptin 100mg DRUG

Sitagliptin 100 mg po once daily.

Also known as: Januvia

Sitagliptin + glargine

Glargine DRUG

Glargine once daily.

Also known as: Lantus

Basal-plus; Sitagliptin + glargine

Lispro DRUG

Correctional doses of lispro if needed for elevated blood glucose using sliding scale insulin (SSI).

Also known as: Humalog

Basal-plus; Sitagliptin + glargine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or female medical non-ICU patients aged 18 - 70 years.
• A known history of type 2 diabetes \> 3 months, receiving either diet alone, oral antidiabetic agents (excluding DPP4 inhibitors), or low-dose (≤ 0.5 units/kg/day) insulin therapy.
• Subjects with BG \>180 mg and \< 400 mg/dL at the time of randomization without laboratory evidence of diabetic ketoacidosis (serum bicarbonate \< 18 mEq/L or positive serum or urinary ketones).
• Written informed consent.

You may not qualify if:

• Age \< 18 or \> 70 years.
• Subjects with increased BG concentration but without a history of diabetes (stress hyperglycemia).
• Subjects with a history of type 1 diabetes.
• Patients with a history of diabetic ketoacidosis or hyperosmolar state.
• Acute critical illness or coronary artery bypass graft (CABG) surgery is expected to require admission to a critical care unit.
• Subjects with gastrointestinal obstruction, adynamic ileus, or those expected to require gastrointestinal suction.
• Unable to take oral food or medications.
• Patients with clinically relevant pancreatic or gallbladder disease.
• Patients with significant hepatic disease (Child-Pugh score B or C) or impaired renal function (GFR \< 50 ml/min).
• Treatment with oral or injectable corticosteroid.
• Mental condition renders the subject unable to understand the study's nature, scope, and possible consequences.
• Female subjects are pregnant or breastfeeding at the time of enrollment into the study.
• Hypersensitivity to sitagliptin or another contraindication to DPP4 inhibitors.
• Subject unable to give informed consent.

Sponsors & Collaborators

• Hospital de Especialidades, Centro Medico Nacional "La Raza", Instituto Mexicano del Seguro Social: lead
• National Polytechnic Institute, Mexico: collaborator

Study Sites (1)

División de Investigación en Salud, Hospital de Especialidades, Centro Médico Nacional "La Raza", IMSS

Mexico City, 02990, Mexico

Location

Related Publications (9)

• Gracia-Ramos AE. Role of incretin-based therapy in hospitalized patients with type 2 diabetes. J Diabetes Investig. 2020 Mar;11(2):508-509. doi: 10.1111/jdi.13130. Epub 2019 Sep 17.

  PMID: 31529777 BACKGROUND

• Gracia-Ramos AE, Carretero-Gomez J, Mendez CE, Carrasco-Sanchez FJ. Evidence-based therapeutics for hyperglycemia in hospitalized noncritically ill patients. Curr Med Res Opin. 2022 Jan;38(1):43-53. doi: 10.1080/03007995.2021.1997288. Epub 2021 Nov 22.

  PMID: 34694181 BACKGROUND

• Gracia-Ramos AE, Cruz-Dominguez MP, Madrigal-Santillan EO. Incretin-based therapy for glycemic control of hospitalized patients with type 2 diabetes: a systematic review. Rev Clin Esp (Barc). 2022 Mar;222(3):180-189. doi: 10.1016/j.rceng.2021.09.003. Epub 2021 Dec 4.

  PMID: 34872879 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.

  PMID: 23877988 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.

  PMID: 27964837 BACKGROUND

• Vellanki P, Rasouli N, Baldwin D, Alexanian S, Anzola I, Urrutia M, Cardona S, Peng L, Pasquel FJ, Umpierrez GE; Linagliptin Inpatient Research Group. Glycaemic efficacy and safety of linagliptin compared to a basal-bolus insulin regimen in patients with type 2 diabetes undergoing non-cardiac surgery: A multicentre randomized clinical trial. Diabetes Obes Metab. 2019 Apr;21(4):837-843. doi: 10.1111/dom.13587. Epub 2018 Dec 17.

  PMID: 30456796 BACKGROUND

• Garg R, Schuman B, Hurwitz S, Metzger C, Bhandari S. Safety and efficacy of saxagliptin for glycemic control in non-critically ill hospitalized patients. BMJ Open Diabetes Res Care. 2017 Mar 29;5(1):e000394. doi: 10.1136/bmjdrc-2017-000394. eCollection 2017.

  PMID: 28405346 BACKGROUND

• 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.

  PMID: 35017617 BACKGROUND

• Gracia-Ramos AE, Cruz-Dominguez MDP, Madrigal-Santillan EO, Rojas-Martinez R, Morales-Gonzalez JA, Morales-Gonzalez A, Hernandez-Espinoza M, Vargas-Penafiel J, Tapia-Gonzalez MLA. Efficacy and safety of sitagliptin with basal-plus insulin regimen versus insulin alone in non-critically ill hospitalized patients with type 2 diabetes: SITA-PLUS hospital trial. J Diabetes Complications. 2024 May;38(5):108742. doi: 10.1016/j.jdiacomp.2024.108742. Epub 2024 Apr 3.

  PMID: 38581842 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sitagliptin Phosphate; Insulin Glargine; Insulin Lispro

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Insulin, Short-Acting

Study Officials

• Abraham Edgar Gracia-Ramos, MD, MSc

  Hospital General, Centro Médico Nacional "La Raza", IMSS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: July 6, 2022
• First Posted: October 13, 2022
• Study Start: July 6, 2022
• Primary Completion: August 14, 2023
• Study Completion: August 24, 2023
• Last Updated: September 26, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)