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

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.

Timeline

Start

2016-05

Primary completion

2016-08

Completion

2018-07

Publications

• Haedersdal S, Lund A, Nielsen-Hannerup E, Maagensen H, van Hall G, Holst JJ, Knop FK, Vilsboll T. The Role of Glucagon in the Acute Therapeutic Effects of SGLT2 Inhibition. Diabetes. 2020 Dec;69(12):2619-2629. doi: 10.2337/db20-0369. Epub 2020 Oct 1.
• Cox AR, Chernis N, Bader DA, Saha PK, Masschelin PM, Felix JB, Sharp R, Lian Z, Putluri V, Rajapakshe K, Kim KH, Villareal DT, Armamento-Villareal R, Wu H, Coarfa C, Putluri N, Hartig SM. STAT1 Dissociates Adipose Tissue Inflammation From Insulin Sensitivity in Obesity. Diabetes. 2020 Dec;69(12):2630-2641. doi: 10.2337/db20-0384. Epub 2020 Sep 29.

Drugs

Indications