Effects of Linagliptin in Addition to Empagliflozin on Islet Cell Physiology

Study Overview
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Brief Summary
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The primary aim of this exploratory mechanistic study is to investigate the effects of Empagliflozin and Linagliptin on alpha- and beta cell physiology in T2DM patients. This study aims to evaluate the effect of the DPP-IV inhibitor linagliptin (as compared to placebo) in addition to the SGLT-2 inhibitor empagliflozin on pancreatic alpha and beta cell function, as well as several markers of metabolic control.

Detailed Description
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This study will be performed as a multi-center study which includes 2 centres. 44 subjects with T2DM are to be included according to the defined in- and exclusion criteria. Subjects has to be on a stable metformin therapy and will receive in a first step empagliflozin for 30 days. Both therapies (metformin and empagliflozin) will be continued for another 30 days and subjects will be randomized to receive in addition Linagliptin or Placebo for 30 days. Subjects will come for two inhouse periods to their corresponding study center and will undergo an hyperglycaemic clamp test as well as a Meal test in each of the periods.

Official Title
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Effects of Linagliptin in Addition to Empagliflozin on Islet Cell Physiology and Metabolic Control in Patients With Type 2 Diabetes Mellitus on Stable Metformin Treatment

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Linagliptin
* Other: Placebo
* Drug: Empagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subject with diabetes mellitus type 2 Diabetes mellitus type 2 on stable treatment with metformin (daily dose at least 1000 mg) for at least 6 months HbA1c 7.0%-9.9%, both inclusive Diabetes duration of at least 24 months) Exclusion Criteria: History of diabetes mellitus type 1 GFR (as calculated by the Cockcroft-Gault equation) < 60 ml/min at Screening Systolic blood pressure outside the range of 100-160 mmHg or diastolic blood pressure above 95 mmHg at Screening

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Empagliflozin plus Linagliptin<br>Linagliptin 5mg to be adminstered for 30 days in T2DM patients on stable metformin and Empagliflozin | Drug: Linagliptin<br>* 22 subjects will receive Linagliptin for 30 days<br>* Other names: Trajenta;Drug: Empagliflozin<br>* 44 subjects will receive Empagliflozin for 60 days<br>* Other names: Jardiance;|
| Placebo Comparator: Empagliflozin plus Placebo<br>Placebo to be adminstered for 30 days in T2DM patients on stable metformin and Empagliflozin | Other: Placebo<br>* 22 subjects will receive Placebo for 30 days<br>Drug: Empagliflozin<br>* 44 subjects will receive Empagliflozin for 60 days<br>* Other names: Jardiance;|
| Other: Empagliflozin<br>Empagliflozin 25mg will be adminstered for 30 days in T2DM patients | Drug: Empagliflozin<br>* 44 subjects will receive Empagliflozin for 60 days<br>* Other names: Jardiance;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • Change in glucagon release (AUC0-180 min) during Liquid Meal Test (LMT) from V3 to V4 between the two treatment groups (Linagliptin vs. placebo) |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • Change in glucagon release (AUC0-180 min) during LMT from V2 to V3 during treatment with Empagliflozin (V2 vs. V3) |  | 30 days |