DPP-4 Inhibitor and Serum BNP Level of Diabetic Patients With Congestive Heart Failure

Study Overview
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Brief Summary
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We thought to investigate the influence of DPP-4 inhibitor on the serum BNP level of diabetic patients with congestive heart failure. This study consists of two protocols. In the first protocol, diabetic patients with high level of serum BNP (100-2000 pg/ml) receiving outpatient treatment with any type of DPP-4 inhibitor at our institution will be enrolled. After baseline data collection, DPP-4 inhibitor will be suspended for one month and serum BNP will be measured. The DPP-4 inhibitor will be resumed and after another month, serum BNP will be measured again. In the other protocol, diabetic patients who were hospitalized due to heart failure were enrolled. DPP-4 inhibitor will be started (if the patient is not taking a DPP-4 inhibitor) or suspended (if the patient is taking a DPP-4 inhibitor) after stabilization of heart failure, and serum BNP will be measured before and after the drug administration or suspension.

Official Title
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Investigation of the Impact of Dipeptidyl Peptidase-4 (DPP-4) Inhibition on Serum B-type Natriuretic Peptide (BNP) Level of Diabetic Patients With Congestive Heart Failure.

Conditions
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Diabetes Mellitus, Heart Failure

Intervention / Treatment
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* Drug: Suspending DPP-4 inhibitor, in outpatient service
* Drug: Starting DPP-4 inhibitor after treatment of heart failure
* Drug: Suspending DPP-4 inhibitor after treatment of heart failure


Participation Criteria
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Eligibility Criteria
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Outpatient arm Inclusion Criteria: Type 2 diabetes patient with congestive heart failure under treatment with DPP-4 inhibitor (sitagliptin, vildagliptin, alogliptin, linagliptin, teneligliptin, anagliptin or saxagliptin) . High serum BNP (100-2000pg/ml). Patients who have given informed consent to participation in the study. Exclusion Criteria: HbA1c over 9.0%. Patients who changed medication within 1 months before inclusion. Judged as ineligible by clinical investigators. Hospitalization arm Inclusion Criteria: Type 2 diabetes patient who were hospitalized for congestive heart failure. Patients who have given informed consent to participation in the study. Exclusion Criteria: Patients on insulin therapy. Judged as ineligible by clinical investigators.

Ages Eligible for Study
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Minimum Age: 20 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Outpatient arm<br>After baseline data collection, DPP-4 inhibitor will be suspended for one month and serum BNP will be measured. The DPP-4 inhibitor will be resumed and after another month, serum BNP will be measured again. | Drug: Suspending DPP-4 inhibitor, in outpatient service<br>* After baseline data collection, DPP-4 inhibitor (sitagliptin, vildagliptin, alogliptin, linagliptin, teneligliptin, anagliptin or saxagliptin) will be suspended for one month and serum BNP will be measured. The DPP-4 inhibitor will be resumed and after another month, serum BNP will be measured again.<br>|
| Experimental: Hospitalization arm 1<br>After hospitalization, medication for diabetes will be suspended. During the treatment for heart failure, drugs other than DPP-4 inhibitor will be resumed when required. After the stabilization of heart failure, DPP-4 inhibitor will be resumed (or administered if it was not prescribed before hospitalization) and serum BNP before and after the initiation of DPP-4 inhibitor will be measured. | Drug: Starting DPP-4 inhibitor after treatment of heart failure<br>* After hospitalization, medication for diabetes will be suspended. During the treatment for heart failure, drugs other than DPP-4 inhibitor will be resumed when required. After the stabilization of heart failure, DPP-4 inhibitor will be resumed (or administered if it was not prescribed before hospitalization) and serum BNP before and after the initiation of DPP-4 inhibitor will be measured.<br>|
| Experimental: Hospitalization arm 2<br>After hospitalization, medication for diabetes may be suspended or continued. During the treatment for heart failure, drugs including DPP-4 inhibitor will be resumed when required. After the stabilization of heart failure, DPP-4 inhibitor will be suspended and serum BNP before and after the suspension of DPP-4 inhibitor will be measured. | Drug: Suspending DPP-4 inhibitor after treatment of heart failure<br>* After hospitalization, medication for diabetes may be suspended or continued. During the treatment for heart failure, drugs including DPP-4 inhibitor will be resumed when required. After the stabilization of heart failure, DPP-4 inhibitor will be suspended and serum BNP before and after the suspension of DPP-4 inhibitor will be measured.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum BNP level with and without DPP-4 inhibitor use. | In the outpatient arm, changes in serum BNP level measured 1 month after suspension of DPP-4 inhibitor, and 1month after resumption of the DPP-4 inhibitor will be analyzed. In the hospitalization arm, serum BNP before and 2-3 days after the initiation of DPP-4 inhibitor will be measured and compared. | 3 days to 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality | Any deaths during the study period. (only for the outpatient arm) | 2 months | 
| Cardiovascular death | Any cardiovascular deaths during the study period. (only for the outpatient arm) | 2 months | 
| Heart failure hospitalization | Any hospitalization due to worsening of heart failure during suspension of or within 1month after resumption of taking a DPP-4 inhibitor. (only for the outpatient arm) | 2 months | 
| Worsening heart failure | Worsening of heart failure after the initiation of DPP-4 inhibitor. (only for the hospitalization arm) | 3 days | 
| Echocardiographic measures (Changes in echocardiographic measures during the study period.) |  | 3 days to 2 months | 
| Other neurohormonal factors (Changes in plasma renin, aldosterone, serum stromal cell-derived factor 1 alpha, serum active glucagon-like peptide-1, serum active glucose-dependent insulinotropic polypeptid) | Changes in plasma renin, aldosterone, serum stromal cell-derived factor 1 alpha, serum active glucagon-like peptide-1, serum active glucose-dependent insulinotropic polypeptide during the study period. | 3 days to 2 months |