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. 2021 Mar 31;8(3):002352.
doi: 10.12890/2021_002352. eCollection 2021.

Successful Use of a GLP-1 Receptor Agonist as Add-on Therapy to Sulfonylurea in the Treatment of KCNJ11 Neonatal Diabetes

Morten Hindsø  1 , Christoffer Martinussen  1 , Maria Saur Svane  1 , Simon Veedfald  2 , Birthe Gade-Rasmussen  1 , Torben Hansen  3 , Sten Madsbad  1
Affiliations

Successful Use of a GLP-1 Receptor Agonist as Add-on Therapy to Sulfonylurea in the Treatment of KCNJ11 Neonatal Diabetes

Morten Hindsø et al. Eur J Case Rep Intern Med. .

Abstract

Sulfonylurea monotherapy is the standard treatment for patients with the most common form of permanent neonatal diabetes, KCNJ11 neonatal diabetes, but it is not always sufficient. For the first time, we present a case of successful use of a GLP-1 receptor agonist as add-on therapy in the treatment of a patient with KCNJ11 neonatal diabetes and insufficient effect of sulfonylurea monotherapy. Good glycaemic control was maintained with a HbA1c level of 48 mmol/mol (6.5%) at the end of 26 months' follow-up.

Learning points: Genetic testing is important in patients with neonatal diabetes.Sulfonylurea is the standard treatment for patients with the most common mutation (KCNJ11).We present the novel use of a GLP-1 receptor agonist as effective add-on therapy in a patient with KCNJ11 neonatal diabetes and insufficient effect of sulfonylurea monotherapy.

Keywords: GLP-1; KCNJ11; Neonatal diabetes; sulfonylurea.

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Conflict of interest statement

Conflicts of Interests: The authors did not receive funding for this work. MSS has received funding from the Danish Diabetes Academy for research not related to this work. SM has received research funding from Novo Nordisk and Boehringer-Ingelheim and honoraria from AstraZeneca, MSD, Sanofi and Novo Nordisk for research activities not related to this work.

Figures

Figure 1
Figure 1
Illustration of selected insulin secretion signalling pathways in the pancreatic β-cell. Activation of the insulin secretion pathway requires closure of the ATP-sensitive potassium channel which in healthy persons is triggered by glucose degradation leading to increased intracellular ATP. In persons with KCNJ11 mutations, the Kir6.2- subunit of the KATP channel is defective and closure of the channel requires treatment with sulfonylurea, which binds to the SUR1-subunit of the channel. GLP-1 receptor agonists potentate an already active insulin secretion pathway by binding and activating the GLP-1 receptor. ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; GLP-1, glucagon-like peptide 1; GLUT2, glucose transporter 2; KATP, ATP-sensitive potassium channel; SUR-1, sulfonylurea receptor-1
Figure 2
Figure 2
HbA1c response to treatment and intercurrent illness
Figure 3
Figure 3
Plasma glucose and serum C-peptide concentrations during liquid mixed meal tests (A and B) and intravenous arginine stimulation tests (C and D), before initiation of glibenclamide treatment (white circles) and 9 months after initiation of glibenclamide treatment (black circles)
See this image and copyright information in PMC

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