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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Efficacy and Safety of Sitagliptin and Glargine Compared to a Basal-plus Insulin Regimen in Hospitalized Patients With Type 2 Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Sitagliptin 100mg
* Drug: Glargine
* Drug: Lispro


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitagliptin + glargine<br>Sitagliptin and glargine once daily + correction doses of lispro if needed. | Drug: Sitagliptin 100mg<br>* Sitagliptin 100 mg po once daily.<br>* Other names: Januvia;Drug: Glargine<br>* Glargine once daily.<br>* Other names: Lantus;Drug: Lispro<br>* Correctional doses of lispro if needed for elevated blood glucose using sliding scale insulin (SSI).<br>* Other names: Humalog;|
| Active Comparator: Basal-plus<br>Glargine once daily plus correction doses of lispro if needed. | Drug: Glargine<br>* Glargine once daily.<br>* Other names: Lantus;Drug: Lispro<br>* Correctional doses of lispro if needed for elevated blood glucose using sliding scale insulin (SSI).<br>* Other names: Humalog;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of blood glucose readings in 100-180 mg/dL range | Percentage of BG readings in the desired range of 100-180 mg/dl out of all avaialble BG readings. | During hospitalization, up to 10 days | 
| Dose of Insulin | Average daily amount of insulin used. | During hospitalization, up to 10 days | 
| Incidence of hypoglycemia (BG <70 mg/dL) | Number of BG readings <70 mg/dL in each group. | During hospitalization, up to 10 days | 
| Percentage of blood glucose reading >180 mg/dL | Percentage of BG reading >180 mg/dL | During hospitalization, up to 10 days | 
| Mean length of stay in days in the hospital among different groups | The duration of stay in days in the hospital between the two groups is calculated and mean number of days is measured. | During hospitalization, up to 10 days |