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

NCT ID: NCT05579119

Last Updated: 2023-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-06
• Study Completion Date: 2023-08-24

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.

Detailed Description

Patients with a known history of diabetes will be randomized to receive sitagliptin plus basal (glargine) insulin or a basal-plus regimen with glargine. Both groups will receive correction doses of rapid-acting insulin lispro in the presence of hyperglycemia (BG >180 mg/dL) per sliding scale. The overall hypothesis is that treatment with sitagliptin in combination with basal insulin will result in better glycemic control and a lower frequency of hypoglycemic events than treatment with a basal-plus insulin regimen in patients with type 2 diabetes in the hospital setting.

68 subjects with type 2 diabetes will be recruited for this study.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sitagliptin + glargine

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

Group Type: EXPERIMENTAL

Sitagliptin 100mg

Intervention Type: DRUG

Sitagliptin 100 mg po once daily.

Glargine

Intervention Type: DRUG

Glargine once daily.

Lispro

Intervention Type: DRUG

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

Basal-plus

Glargine once daily plus correction doses of lispro if needed.

Group Type: ACTIVE_COMPARATOR

Glargine

Intervention Type: DRUG

Glargine once daily.

Lispro

Intervention Type: DRUG

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

Interventions

Sitagliptin 100mg

Sitagliptin 100 mg po once daily.

Intervention Type: DRUG

Glargine

Glargine once daily.

Intervention Type: DRUG

Lispro

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

Intervention Type: DRUG

Other Intervention Names

Januvia; Lantus; Humalog

Eligibility Criteria

Inclusion Criteria

1. Males or female medical non-ICU patients aged 18 - 70 years.

2. 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.

3. 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).

4. Written informed consent.

Exclusion Criteria

1. Age < 18 or > 70 years.

2. Subjects with increased BG concentration but without a history of diabetes (stress hyperglycemia).

3. Subjects with a history of type 1 diabetes.

4. Patients with a history of diabetic ketoacidosis or hyperosmolar state.

5. Acute critical illness or coronary artery bypass graft (CABG) surgery is expected to require admission to a critical care unit.

6. Subjects with gastrointestinal obstruction, adynamic ileus, or those expected to require gastrointestinal suction.

7. Unable to take oral food or medications.

8. Patients with clinically relevant pancreatic or gallbladder disease.

9. Patients with significant hepatic disease (Child-Pugh score B or C) or impaired renal function (GFR < 50 ml/min).

10. Treatment with oral or injectable corticosteroid.

11. Mental condition renders the subject unable to understand the study's nature, scope, and possible consequences.

12. Female subjects are pregnant or breastfeeding at the time of enrollment into the study.

13. Hypersensitivity to sitagliptin or another contraindication to DPP4 inhibitors.

14. Subject unable to give informed consent.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Polytechnic Institute, Mexico

OTHER

Sponsor Role: collaborator

Hospital de Especialidades, Centro Medico Nacional "La Raza", Instituto Mexicano del Seguro Social

OTHER

Sponsor Role: lead

Responsible Party

Abraham Edgar Gracia-Ramos

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Abraham Edgar Gracia-Ramos, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

Mexico City, , Mexico

Countries

Mexico

References

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.

Reference Type: BACKGROUND

PMID: 31529777 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34694181 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34872879 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 23877988 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27964837 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30456796 (View on PubMed)

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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

PMID: 35017617 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38581842 (View on PubMed)

Other Identifiers

R-2021-3501-078

Identifier Type: -

Identifier Source: org_study_id