The Role of Glucagon in the Effects of Dipeptidyl Peptidase-4 Inhibitors and Sodium-glucose Co-transporter-2 Inhibitors

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-31

Study Completion Date

2018-07-31

Brief Summary

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In normal physiology, glucagon from pancreatic alpha cells plays an important role in maintaining glucose homeostasis via its regulatory effect on hepatic glucose production. Patients with type 2 diabetes exhibit elevated plasma glucagon levels in the fasting state, and in response to ingestion of glucose or a mixed meal.glucagon, glucagon concentrations fail to decrease appropriately and may even increase. This diabetic hyperglucagonaemia may therefore contribute importantly to the hyperglycaemia of the patients.

Several glucose-lowering treatment modalities have been shown to affect glucagon levels in patients with type 2 diabetes, but the role of glucagon in the glucose-lowering effects of these treatment modalities has been difficult to discern. By using a glucagon receptor antagonist (GRA) the investigators will exploit glucagon receptor antagonism to delineate the role of glucagon during treatment with sodium-glucose co-transporter 2 (SGLT2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors, which have been shown to increase and decrease plasma glucagon levels, respectively.

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Detailed Description

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Conditions

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Type 2 Diabetes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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A1: GRA-placebo + MEAL + DPP4-placebo

LY2409021 placebo + 4 hour standardised liquid mixed-meal test + linagliptin placebo

Group Type PLACEBO_COMPARATOR

LY2403021 placebo

Intervention Type DRUG

Standardised liquid meal

Intervention Type PROCEDURE

Linagliptin placebo

Intervention Type DRUG

A2: GRA-active + MEAL + DPP4-placebo

300 mg LY2409021 + 4 hour standardised liquid mixed-meal test + linagliptin placebo

Group Type PLACEBO_COMPARATOR

LY2403021

Intervention Type DRUG

Glucagon receptor antagonist

Standardised liquid meal

Intervention Type PROCEDURE

Linagliptin placebo

Intervention Type DRUG

A3: GRA-placebo + MEAL + DPP4-active

LY2409021 placebo + 4 hour standardised liquid mixed-meal test + 5 mg linagliptin (Trajenta)

Group Type ACTIVE_COMPARATOR

LY2403021 placebo

Intervention Type DRUG

Standardised liquid meal

Intervention Type PROCEDURE

Linagliptin

Intervention Type DRUG

DPP-4-inhibitor

A4: GRA-active + MEAL + DPP4-active

300 mg LY2409021 + 4 hour standardised liquid mixed-meal test + 5 mg linagliptin (Trajenta)

Group Type ACTIVE_COMPARATOR

LY2403021

Intervention Type DRUG

Glucagon receptor antagonist

Standardised liquid meal

Intervention Type PROCEDURE

Linagliptin

Intervention Type DRUG

DPP-4-inhibitor

B1: GRA-placebo + MEAL + SGLT2-placebo

LY2409021 placebo + 4 hour standardised liquid mixed-meal test + empagliflozin placebo

Group Type PLACEBO_COMPARATOR

LY2403021 placebo

Intervention Type DRUG

Standardised liquid meal

Intervention Type PROCEDURE

Empagliflozin placebo

Intervention Type DRUG

B2: GRA-active + MEAL + SGLT2-placebo

300 mg LY2409021 + 4 hour standardised liquid mixed-meal test + empagliflozin placebo

Group Type PLACEBO_COMPARATOR

LY2403021

Intervention Type DRUG

Glucagon receptor antagonist

Standardised liquid meal

Intervention Type PROCEDURE

Empagliflozin placebo

Intervention Type DRUG

B3: GRA-placebo + MEAL + SGLT2-active

LY2409021 placebo + 4 hour standardised liquid mixed-meal test + 25 mg empagliflozin (Jardiance)

Group Type ACTIVE_COMPARATOR

LY2403021 placebo

Intervention Type DRUG

Standardised liquid meal

Intervention Type PROCEDURE

Empagliflozin

Intervention Type DRUG

SGLT2-inhibitor

B4: GRA-active + MEAL + SGLT2-active

300 mg LY2409021 + 4 hour standardised liquid mixed-meal test + 25 mg empagliflozin (Jardiance)

Group Type ACTIVE_COMPARATOR

LY2403021

Intervention Type DRUG

Glucagon receptor antagonist

Standardised liquid meal

Intervention Type PROCEDURE

Empagliflozin

Intervention Type DRUG

SGLT2-inhibitor

Interventions

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LY2403021

Glucagon receptor antagonist

Intervention Type DRUG

LY2403021 placebo

Intervention Type DRUG

Standardised liquid meal

Intervention Type PROCEDURE

Linagliptin

DPP-4-inhibitor

Intervention Type DRUG

Linagliptin placebo

Intervention Type DRUG

Empagliflozin

SGLT2-inhibitor

Intervention Type DRUG

Empagliflozin placebo

Intervention Type DRUG

Other Intervention Names

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Trajenta Jardiance

Eligibility Criteria

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Inclusion Criteria

* Caucasians above 30 years of age with diet or metformin treated type 2 diabetes for at least 3 months (diagnosed according to the criteria of the World Health Organization)
* Normal haemoglobin
* Informed consent

Exclusion Criteria

* Inflammatory bowel disease
* Intestinal resections
* Nephropathy (serum creatinine above normal range and/or albuminuria)
* Liver disease (serum alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) \>2×normal values)
* Treatment with medicine that cannot be paused for 12 hours
* Pregnancy and/or breastfeeding
* Family history of pancreatic islet tumours
* Age above 75 years
* Treatment with loop-diuretics (applies only to arms with empagliflozin or empagliflozin placebo)
* Chronic heart failure

Minimum Eligible Age

30 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No