Improvement in glycaemic parameters using SGLT-2 inhibitor and GLP-1 agonist in combination in an adolescent with diabetes mellitus and Prader-Willi syndrome: a case report

Toby Candler; David McGregor; Kruthika Narayan; Chris Moudiotis; Christine P. Burren

doi:10.1515/jpem-2019-0389

Article

Improvement in glycaemic parameters using SGLT-2 inhibitor and GLP-1 agonist in combination in an adolescent with diabetes mellitus and Prader-Willi syndrome: a case report

Toby Candler , David McGregor , Kruthika Narayan , Chris Moudiotis and Christine P. Burren

Published/Copyright: May 24, 2020

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 33 Issue 7

Abstract

Objectives

Prader-Willi Syndrome (PWS) is characterised by hyperphagia often leading to obesity; a known risk factor for insulin resistance and type 2 (T2) diabetes. We present a prepubertal girl with PWS who developed diabetes.

Case presentation

Our case was diagnosed with PWS in infancy following investigation for profound central hypotonia and feeding difficulties. She commenced growth hormone (GH) aged 8 years for short stature and treatment improved linear growth. At age 12 years, she presented with polydipsia, polyuria and vulvovaginitis. She was overweight (BMI SDS +1.43). Diabetes was diagnosed (Blood glucose = 24.2 mmol/L, HbA1c = 121 mmol/mol or 13.2%). She was not acidotic and had negative blood ketones. Autoantibodies typical of type 1 diabetes were negative. She was initially treated with basal bolus insulin regime. GH was discontinued 3 months later due to concerns regarding GH-induced insulin resistance. Off GH, insulin requirements reduced to zero, allowing Metformin monotherapy. However off GH, she reported significant lethargy with static growth and increased weight. Combinations of Metformin with differing insulin regimes did not improve glucose levels. Liraglutide (GLP-1 agonist) and Metformin did not improve glucose levels nor her weight. Liraglutide and Empaglifozin (SGLT-2 inhibitor) therapy used in combination were well tolerated and demonstrated rapid normalisation of blood glucose and improvement in her HbA1c to within target (48 mmol/mol) which was sustained after 6 months of treatment.

Conclusions

Newer treatments for type 2 diabetes (e. g. GLP-1 agonists or SGLT-2 inhibitors) offer potential treatment options for those with diabetes and PWS when conventional treatments are ineffective.

What is new?

DM (Diabetes mellitus) is a rare complication of Prader-Willi Syndrome (PWS) before puberty.
This case demonstrates the challenges of managing PWS and DM including negotiating growth hormone therapy and pubertal induction/augmentation.
Conventional therapies (e. g. oral hypoglycaemic agents and insulin) failed to achieve adequate glycaemic parameters.
Recently developed therapies of Liraglutide (GLP-1) and Empaglifozin (SGLT-2 inhibitor) used combination were well tolerated, led to rapid normalisation of blood glucose and a sustained improvement in HbA1c within target.
This is the first case report describing the use of a GLP-1 agonist and a SGLT-2 inhibitor used in combination in a child with PWS and DM.

Keywords: children and adolescents; incretin therapies; Prader-Willi syndrome; SGLT-2 inhibitors

Corresponding author: Dr. Toby Candler, Department of Paediatric Endocrinology, Bristol Royal Hospital for Children, University Hospitals Bristol NHS Foundation Trust, Bristol, UK; and Medical Research Council The Gambia at London School of Hygiene and Tropical Medicine, London, UK, E-mail: tcandler@mrc.gm

Acknowledgements

We would like to thank Mrs Julie McGregor for the help designing Figure 1.

Research funding: There was no specific funding for this article. TC is currently funded through an MRC (Medical Research Council) Clinical Research Training Fellowship.
Author contributions: TC led the writing of the manuscript. TC, DM, KN, CM and CB were involved in the clinical management. All authors approved the manuscript.
Competing interests: The authors have no conflicts of interest to disclose

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Received: 2019-09-10

Revised: 2020-01-27

Accepted: 2020-04-01

Published Online: 2020-05-24

Published in Print: 2020-07-28

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Articles in the same Issue

https://doi.org/10.1515/jpem-2019-0389

Keywords for this article

children and adolescents; incretin therapies; Prader-Willi syndrome; SGLT-2 inhibitors