Gastrin analogue administration adds no significant glycaemic benefit to a glucagon‐like peptide‐1 receptor agonist acutely or after washout of both analogues. Issue 7 (21st April 2019)

• Record Type: Journal Article
• Authors: Bokvist, Krister; Ding, Ying; Landschulz, William H.; Sinha, Vikram; Pastrak, Aleksandra; Belin, Ruth M.
• Is Part Of: Diabetes, obesity & metabolism. Volume 21:Issue 7(2019)
• Page Start: 1606
• Page End: 1614
• Publication Date: 2019-04-21
• Subjects: combination therapy -- gastrin -- GLP‐1 receptor agonist -- type 2 diabetes -- β‐cell function; Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.13695
• Languages: English
• ISSNs: 1462-8902

Abstract

Abstract: Aim: To determine if a 4‐week course of 14 mg weekly GLP‐1 agonist LY2428757 combined with 3 mg or 2 mg daily gastrin analogue TT223 (LY+TT223) results in long‐term glycaemic changes. Materials and methods: Patients with in adequately‐controlled type 2 diabetes mellitus ±metformin (N=151) were randomized to a 4‐week course of LY+TT223 (3 mg), LY+TT223 (2 mg), LY+TT223 placebo (LY‐only) or LY placebo+TT223 placebo (placebo). The primary objective was change in HbA1c from baseline to 5 month safter completion of therapy (i.e. at 6 months) and safety and tolerability with LY+TT223 versus LY‐only. Results: LY groups showed HbA1c reductions during the active treatment phase. These did not persist during follow‐up phase. Combining TT223 with LY did not result in additional glycaemic effects during treatment or follow‐up. At 6 months, LSM ± SE for change in HbA1c from baseline was: LY+TT223 (3 mg): ‐0.1 ± 0.2%; LY+TT223 (2 mg): 0.1 ± 0.2%; LY‐only: ‐0.2 ± 0.2%; placebo: 0.04 ± 0.2%. Secondary analyses were consistent with primary results. LY+TT223 was not superior to LY for other time points or end points, including insulin secretory response to mixed meal tolerance tests. The most common adverse events (nausea and vomiting) were more frequent with LY+TT223 versus LY‐only. The safety profile was consistent with previous findings. Conclusion: GLP‐1+gastrin combination therapy did not improve glycaemic control versus GLP‐1 alone.