Sitagliptin Therapy in Hospitalized Patients With Type 2 Diabetes

NCT01845831 | Completed Phase 4 Results DMC

• 1 other identifier: IRB00063642
• Study Type: interventional
• Target: 292
• Locations: 1 country
• Sites: 5

Brief Summary

High blood glucose levels in hospitalized patients with diabetes are associated with increased risk of medical complications and death. Improved glucose control with insulin injections may improve clinical outcome and prevent some of the hospital complications. Glargine (Lantus®) insulin injection is the most common treatment of diabetes in the hospital. Sitagliptin (Januvia®)is effective in lowering blood glucose. In a recent pilot study aiming to determine differences in glycemic control between treatment with sitagliptin (Januvia®) alone or in combination with basal insulin and basal bolus regimen in general medicine and surgery patients with type 2 diabetes (T2D). The investigators found that treatment with sitagliptin alone or in combination with basal insulin resulted in similar glycemic control compared to basal bolus regimen. The investigators will conduct a prospective RCT aimed to determine the safety and efficacy of sitagliptin therapy for in-hospital and post-discharge management of general medicine and surgical patients with T2D. A total of 280 patients with known history of diabetes will be randomized to receive sitagliptin plus basal (glargine) insulin once daily (group 1), or basal bolus regimen with glargine once daily and aspart or lispro insulin before meals (group 2). If needed, patients in the treatment groups will receive correction doses of rapid-acting insulin in the presence of hyperglycemia (BG \> 140 mg/dl). The overall hypothesis is that treatment with sitagliptin in combination with basal insulin in patients with type 2 diabetes will result in a similar improvement in hospital and post-discharge glycemic control and in a lower frequency of hypoglycemic events than treatment with basal bolus insulin regimen with glargine once daily and lispro insulin before meals. Patients will be recruited at Grady Memorial Hospital, Emory University Hospital, University of Michigan, Ohio State University and Temple University

Conditions

Type 2 Diabetes

Keywords

Diabetes; DPP4 inhibitors; Sitagliptin; Glargine; RCT; basal insulin; hospital hyperglycemia; inpatient diabetes

Outcome Measures

Primary Outcomes (6)

• Mean Blood Glucose Concentration After First Day of Treatment

  The average blood glucose (BG) concentration after the first day of treatment

  Duration of Hospitalization (Up to 10 Days)

• Mean Percentage of Blood Glucose Readings Between 3.9 - 7.8 mmol/L

  Differences in glycemic control as measured by mean daily blood glucose (BG) concentration between sitagliptin once daily and basal bolus therapy with glargine once daily plus supplemental lispro insulin in hospitalized patients with T2D.

  Duration of Hospitalization (Up to 10 Days)

• Mean Percentage of Blood Glucose Readings Between 3.9 - 10.0 mmol/L

  Differences in glycemic control as measured by mean daily blood glucose (BG) concentration between sitagliptin once daily and basal bolus therapy with glargine once daily plus supplemental lispro insulin in hospitalized patients with T2D.

  Duration of Hospitalization (Up to 10 Days)

• Mean Percentage of Blood Glucose Readings Between 5.6 - 7.8 mmol/L

  Differences in glycemic control as measured by mean daily blood glucose (BG) concentration between sitagliptin once daily and basal bolus therapy with glargine once daily plus supplemental lispro insulin in hospitalized patients with T2D.

  Duration of Hospitalization (Up to 10 Days)

• Mean Percentage of Blood Glucose Readings Greater Than 13.3 mmol/L

  Differences in glycemic control as measured by mean daily blood glucose (BG) concentration between sitagliptin once daily and basal bolus therapy with glargine once daily plus supplemental lispro insulin in hospitalized patients with T2D.

  Duration of Hospitalization (Up to 10 Days)

• Change in HbA1C

  The mean HbA1C measured at 3 months and 6 months post hospitalization. HbA1C is an indicator of diabetes control; below 6.0% is normal, 6.0% to 6.4% indicates prediabetes, and 6.5% or over indicates diabetes.

  Post Hospital Discharge Month 3, Month 6

Secondary Outcomes (5)

• Number of Participants With a Hypoglycemic Event

  Duration of Hospitalization (Up to 10 Days)

• Total Daily Insulin Dose

  Duration of Hospitalization (Up to 10 Days)

• Length of Hospital Stay

  Duration of Hospitalization (Up to 10 Days)

• Acute Renal Failure Rate

  Duration of Hospitalization (Up to 10 Days)

• Hospital Mortality Rate

  Duration of Hospitalization (Up to 10 Days)

Study Arms (5)

Sitagliptin + glargine (Hospital)

EXPERIMENTAL

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

Drug: Sitagliptin; Drug: Glargine

Basal bolus (Hospital)

ACTIVE COMPARATOR

Glargine once daily and rapid-acting insulin before meals + correction doses of aspart or lispro if needed

Drug: Basal Bolus

Metformin and Sitagliptin

EXPERIMENTAL

Patients with HbA1c ≤ 7% will be discharged on the combination of metformin and sitagliptin (Janumet ® 500/50 mg) twice daily for 6 months

Drug: Metformin and Sitagliptin

Metformin and sitagliptin + glargine 50%

EXPERIMENTAL

Patients with HbA1c between 7% and 9% will be discharged on metformin and sitagliptin (Janumet ® 500/50 mg) twice daily plus glargine insulin (50% of the inpatient glargine dose) for 6 months

Drug: Metformin and Sitagliptin; Drug: Glargine 50%

Metformin and sitagliptin + glargine 80%

EXPERIMENTAL

Patients with HbA1c \> 9% will be discharged on metformin and sitagliptin (Janumet ® 500/50 mg) twice daily plus glargine insulin (80% of the inpatient glargine dose) for 6 months

Drug: Metformin and Sitagliptin; Drug: Glargine 80%

Interventions

Sitagliptin DRUG

Sitagliptin will be taken orally at 100 mg or 50 mg once a day per renal function.

Also known as: Januvia

Sitagliptin + glargine (Hospital)

Basal Bolus DRUG

Basal bolus regimen with glargine once daily and rapid-acting insulin (lispro or aspart) before meals + + correction doses of rapid acting insulin if needed

Also known as: Glargine (Lantus) + aspart (Novolog) or lispro (Humalog)

Basal bolus (Hospital)

Metformin and Sitagliptin DRUG

Janumet is a combination of metformin and sitagliptin. Patients with HbA1c ≤ 7% will be discharged on the combination of metformin and sitagliptin (Janumet ® 500/50 mg) twice daily for 6 months.

Also known as: Janumet

Metformin and Sitagliptin; Metformin and sitagliptin + glargine 50%; Metformin and sitagliptin + glargine 80%

Glargine DRUG

Patients with blood glucose between 140-200 mg/dL during hospitalization will receive 0.2 units per kg weight per day. Patients with blood glucose between 201-400 mg/dL during hospitalization will receive 0.25 units per kg weight per day.

Also known as: Lantus

Sitagliptin + glargine (Hospital)

Glargine 50% DRUG

Glargine will be prescribed at 50% of daily hospital dose.

Metformin and sitagliptin + glargine 50%

Glargine 80% DRUG

Glargine will be prescribed at 80% of daily hospital dose.

Metformin and sitagliptin + glargine 80%

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females between the ages of 18 and 80 years admitted to medicine and surgery services.
• A known history of Type 2 Diabetes \> 1 month, receiving either diet alone, oral antidiabetic agents: sulfonylureas and metformin as monotherapy or in combination therapy (excluding DPP-4 inhibitors) or low-dose (≤ 0.6 units/kg/day) insulin therapy.
• Subjects with a blood glucose \>140 mg and \< 400 mg/dL at time of randomization without laboratory evidence of diabetic ketoacidosis (serum bicarbonate \< 18 mEq/L or positive serum or urinary ketones).

You may not qualify if:

• Age \< 18 or \> 80 years.
• Subjects with increased BG concentration, but without a history of diabetes (stress hyperglycemia).
• Subjects with a history of type 1 diabetes (suggested by BMI \< 25 requiring insulin therapy or with a history of diabetic ketoacidosis and hyperosmolar hyperglycemic state, or ketonuria) \[46\].
• Treatment with DPP4 inhibitor or Glucagon like peptide 1 (GLP1) analogs during the past 3 months prior to admission.
• Acute critical illness or coronary artery bypass graft (CABG) surgery expected to require admission to a critical care unit.
• Subjects with gastrointestinal obstruction or adynamic ileus or those expected to require gastrointestinal suction.
• Medical or surgical patients expected to be kept NPO for \>24-48 hours after admission or after completion of surgical procedure.
• Patients with clinically relevant pancreatic or gallbladder disease.
• Patients with acute myocardial infarction, clinically significant hepatic disease or significantly impaired renal function (GFR \< 30 ml/min).
• Treatment with oral or injectable corticosteroid = or \> prednisone 5 mg/per day.
• Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.
• Female subjects are pregnant or breast feeding at time of enrollment into the study.

Sponsors & Collaborators

• Emory University: lead
• Merck Sharp & Dohme LLC: collaborator
• Temple University: collaborator
• University of Michigan: collaborator
• Ohio University: collaborator

Study Sites (5)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Emory University Hospital

Atlanta, Georgia, 30324, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

Sitagliptin Phosphate; Insulin Glargine; Insulin Aspart; Insulin Lispro; Sitagliptin Phosphate, Metformin Hydrochloride Drug Combination

Condition Hierarchy (Ancestors)

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; Metformin; Biguanides; Guanidines; Amidines; Organic Chemicals; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

As a single DPP-4 inhibitor, sitagliptin, was used, results cannot be generalized to other incretin-based drugs. Additionally, the proportion of surgical patients was small, and the results may not be generalized to all surgical patients.

Results Point of Contact

• Title: Dr. Guillermo Umpierrez
• Organization: Emory University

geumpie@emory.edu

404-778-1665

Study Officials

• Guillermo Umpierrez, MD

  Emory University SOM

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: Professor of Medicine

Study Record Dates

• First Submitted: April 30, 2013
• First Posted: May 3, 2013
• Study Start: August 1, 2013
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: May 30, 2017
• Results First Posted: May 30, 2017

Record last verified: 2017-04

Locations

US (5)