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

• Status: Completed
• Trial end date: 2018-07-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Gentofte, Copenhagen
• Collaborator: Eli Lilly and Company
• Treatments: Dipeptidyl-Peptidase IV Inhibitors; Empagliflozin; Glucagon; Glucagon-Like Peptide 1; Linagliptin

Criteria

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