Sitagliptin Therapy in Hospitalized Patients With Type 2 Diabetes

Randomized Controlled Trial on the Safety and Efficacy of Sitagliptin Therapy for the Inpatient Management of General Medicine and Surgery Patients With Type 2 Diabetes

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01845831

Enrollment

292

Registered

2013-05-03

Start date

2013-08-31

Completion date

2016-04-30

Last updated

2017-05-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 2 Diabetes

Keywords

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

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

Detailed description

Specific Aim 1: To determine whether in-hospital glycemic control, as measured by mean daily blood glucose concentration and frequency of hypoglycemic events, is different between treatment with sitagliptin (Januvia®) in combination with basal insulin (glargine) and basal bolus regimen (glargine and rapid-acting insulin analog) in general medicine and surgery patients with T2D. Patients with T2D treated with diet and/or OAD or with low total daily dose insulin therapy (≤0.6 unit/kg/day) will be randomized to receive sitagliptin plus glargine insulin (group 1) or basal bolus regimen with glargine once daily and rapid-acting insulin (lispro or aspart) before meals (group 2). If needed, patients in the 2 treatment groups will receive supplemental (correction) doses of rapid-acting insulin before meals for BG \> 140 mg/dl. Specific Aim 2: To determine the efficacy and safety of an A1C based discharge algorithm in controlling BG after discharge in patients with T2D. Patients who participate in the in-hospital (Aim 1) arm will be invited to enroll in this open label prospective outpatient study. The total duration of the study is 6 months. Patients with HbA1c ≤ 7% will be discharged on the combination of metformin and sitagliptin (Janumet ®) twice daily. Those with HbA1c between 7% and 9% will be discharged on metformin and sitagliptin (Janumet ®) twice daily plus glargine insulin at 50% of the inpatient glargine dose. Those with HbA1c \> 9% will be discharged on metformin and sitagliptin (Janumet ®) twice-daily plus glargine insulin at 80% of the inpatient dose.

Interventions

DRUGSitagliptin

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

DRUGBasal Bolus

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

DRUGMetformin and Sitagliptin

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.

DRUGGlargine

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.

DRUGGlargine 50%

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

DRUGGlargine 80%

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

Inclusion criteria

1. Males or females between the ages of 18 and 80 years admitted to medicine and surgery services. 2. 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. 3. 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).

Exclusion criteria

1. Age \< 18 or \> 80 years. 2. Subjects with increased BG concentration, but without a history of diabetes (stress hyperglycemia). 3. 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) \[46\]. 4. Treatment with DPP4 inhibitor or Glucagon like peptide 1 (GLP1) analogs during the past 3 months prior to admission. 5. Acute critical illness or coronary artery bypass graft (CABG) surgery expected to require admission to a critical care unit. 6. Subjects with gastrointestinal obstruction or adynamic ileus or those expected to require gastrointestinal suction. 7. Medical or surgical patients expected to be kept NPO for \>24-48 hours after admission or after completion of surgical procedure. 8. Patients with clinically relevant pancreatic or gallbladder disease. 9. Patients with acute myocardial infarction, clinically significant hepatic disease or significantly impaired renal function (GFR \< 30 ml/min). 10. Treatment with oral or injectable corticosteroid = or \> prednisone 5 mg/per day. 11. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study. 12. Female subjects are pregnant or breast feeding at time of enrollment into the study.

Design outcomes

Primary

Measure	Time frame	Description
Change in HbA1C	Post Hospital Discharge Month 3, Month 6	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.
Mean Blood Glucose Concentration After First Day of Treatment	Duration of Hospitalization (Up to 10 Days)	The average blood glucose (BG) concentration after the first day of treatment
Mean Percentage of Blood Glucose Readings Between 3.9 - 7.8 mmol/L	Duration of Hospitalization (Up to 10 Days)	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.
Mean Percentage of Blood Glucose Readings Between 3.9 - 10.0 mmol/L	Duration of Hospitalization (Up to 10 Days)	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.
Mean Percentage of Blood Glucose Readings Between 5.6 - 7.8 mmol/L	Duration of Hospitalization (Up to 10 Days)	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.
Mean Percentage of Blood Glucose Readings Greater Than 13.3 mmol/L	Duration of Hospitalization (Up to 10 Days)	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.

Secondary

Measure	Time frame	Description
Total Daily Insulin Dose	Duration of Hospitalization (Up to 10 Days)	Daily insulin requirement (units per day).
Length of Hospital Stay	Duration of Hospitalization (Up to 10 Days)	Length of hospital stay in days.
Acute Renal Failure Rate	Duration of Hospitalization (Up to 10 Days)	Acute renal failure is defined as a clinical diagnosis of acute renal failure with documented new-onset abnormal renal function (increment \> 0.5 mg/dL from baseline).
Hospital Mortality Rate	Duration of Hospitalization (Up to 10 Days)	Mortality is defined as death occurring during admission.
Number of Participants With a Hypoglycemic Event	Duration of Hospitalization (Up to 10 Days)	The number of participants who had a hypoglycemic event during hospitalization.

Countries

United States

Participant flow

Recruitment details

Participants were recruited between August 23, 2013 and July 27, 2015.

Pre-assignment details

Of the 292 subjects who consented for participation, 279 began the inpatient study phase. Two hundred and fifty-three participants began the outpatient study phase.

Participants by arm

Arm	Count
Sitagliptin + Glargine (Hospital) Sitagliptin and glargine once daily + correction doses of aspart or lispro if needed Sitagliptin + glargine: Sitagliptin and Glargine once daily + correction doses of rapid acting insulin if needed	138
Basal Bolus (Hospital) Glargine once daily and rapid-acting insulin before meals + correction doses of aspart or lispro if needed Basal Bolus: Basal bolus regimen with glargine once daily and rapid-acting insulin (lispro or aspart) before meals + correction doses of rapid acting insulin if needed	139
Total	277

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Inpatient Phase	Withdrawal by Subject	1	1	0	0	0

Baseline characteristics

Characteristic	Total	Sitagliptin + Glargine (Hospital)	Basal Bolus (Hospital)
Age, Continuous	56.9 years STANDARD_DEVIATION 10.9	56.8 years STANDARD_DEVIATION 11.4	57.1 years STANDARD_DEVIATION 10.4
Race/Ethnicity, Customized Black	159 Participants	81 Participants	78 Participants
Race/Ethnicity, Customized Other	26 Participants	12 Participants	14 Participants
Race/Ethnicity, Customized White	89 Participants	45 Participants	44 Participants
Sex: Female, Male Female	111 Participants	59 Participants	52 Participants
Sex: Female, Male Male	166 Participants	79 Participants	87 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 138	0 / 139
other Total, other adverse events	2 / 138	1 / 139
serious Total, serious adverse events	10 / 138	9 / 139

Outcome results

Primary

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.

Time frame: Post Hospital Discharge Month 3, Month 6

Population: 253 subjects who participated in the inpatient phase and were invited to complete the outpatient phase.

Arm	Measure	Group	Value (MEAN)	Dispersion
Sitagliptin + Glargine (Hospital)	Change in HbA1C	Month 3	6.3 percent	Standard Deviation 0.8
Sitagliptin + Glargine (Hospital)	Change in HbA1C	Baseline	6.3 percent	Standard Deviation 0.5
Sitagliptin + Glargine (Hospital)	Change in HbA1C	Month 6	6.2 percent	Standard Deviation 1
Basal Bolus (Hospital)	Change in HbA1C	Month 6	7.3 percent	Standard Deviation 1.3
Basal Bolus (Hospital)	Change in HbA1C	Baseline	8.0 percent	Standard Deviation 0.6
Basal Bolus (Hospital)	Change in HbA1C	Month 3	7.3 percent	Standard Deviation 1.1
Metformin and Sitagliptin + Glargine 80%	Change in HbA1C	Month 3	8.0 percent	Standard Deviation 1.8
Metformin and Sitagliptin + Glargine 80%	Change in HbA1C	Month 6	8.0 percent	Standard Deviation 2
Metformin and Sitagliptin + Glargine 80%	Change in HbA1C	Baseline	11.3 percent	Standard Deviation 1.7

Primary