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

Sponsor
University Hospital, Gentofte, Copenhagen
Study ID
NCT02792400
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
30 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • LY2403021 — DRUG
    Glucagon receptor antagonist
  • LY2403021 placebo — DRUG
  • Standardised liquid meal — PROCEDURE
  • Linagliptin — DRUG
    DPP-4-inhibitor
  • Linagliptin placebo — DRUG
  • Empagliflozin — DRUG
    SGLT2-inhibitor
  • Empagliflozin placebo — DRUG

Study Details

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.

Key Dates

Start date
May 31, 2016
Status verified
Nov 2017
Primary completion
Aug 31, 2016
Completion
Jul 31, 2018

Study Design

Enrollment
24 participants (actual)
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE

Arms

  • Placebo Comparator: A1: GRA-placebo + MEAL + DPP4-placebo
    LY2409021 placebo + 4 hour standardised liquid mixed-meal test + linagliptin placebo
  • Placebo Comparator: A2: GRA-active + MEAL + DPP4-placebo
    300 mg LY2409021 + 4 hour standardised liquid mixed-meal test + linagliptin placebo
  • Active Comparator: A3: GRA-placebo + MEAL + DPP4-active
    LY2409021 placebo + 4 hour standardised liquid mixed-meal test + 5 mg linagliptin (Trajenta)
  • Active Comparator: A4: GRA-active + MEAL + DPP4-active
    300 mg LY2409021 + 4 hour standardised liquid mixed-meal test + 5 mg linagliptin (Trajenta)
  • Placebo Comparator: B1: GRA-placebo + MEAL + SGLT2-placebo
    LY2409021 placebo + 4 hour standardised liquid mixed-meal test + empagliflozin placebo
  • Placebo Comparator: B2: GRA-active + MEAL + SGLT2-placebo
    300 mg LY2409021 + 4 hour standardised liquid mixed-meal test + empagliflozin placebo
  • Active Comparator: B3: GRA-placebo + MEAL + SGLT2-active
    LY2409021 placebo + 4 hour standardised liquid mixed-meal test + 25 mg empagliflozin (Jardiance)
  • Active Comparator: B4: GRA-active + MEAL + SGLT2-active
    300 mg LY2409021 + 4 hour standardised liquid mixed-meal test + 25 mg empagliflozin (Jardiance)

Primary Outcome Measure

Difference in postprandial glucose excursions (linagliptin) [ Time Frame: Area under the curve (AUC) time frame: 0, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 105, 120, 150, 180, 210, 240 minutes. Comparison between experimental days with linagliptin (A1, A2, A3, A4) ]

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