Pharmacological management of diabetes in severe mental illness: A comprehensive clinical review of efficacy, safety and tolerability

There is increasing evidence that people with severe mental illness (SMI) have considerably worse physical health than the general population.

A recent study published in the Expert Review of Clinical Pharmacology summarises the published efficacy and tolerability of pharmacotherapeutic interventions in type 2 diabetes mellitus (T2DM) in severe mental illness (SMI), focusing on glucose lowering therapies. In doing so, the authors have provided a treatment algorithm for the management of Type 2 Diabetes in people with schizophrenia and other psychotic disorders.

The study was a cross specialty collaboration, with Dr John Lally (Senior Clinical Lecturer, School of Medicine and Medical Sciences, University College Dublin, St Vincent’s University Hospital, Dublin), Professor Donal O Shea (Consultant Endocrinologist and HSE National Clinical Lead for Obesity Ireland) and Dr Aonghus O Loughlin (Consultant Endocrinologist, Bons Secour Hospital, Galway) as co-authors, along with Professor Allys Guerandel (St Vincent’s University Hospital), and international collaborators including Dr Fiona Gaughran (National Psychosis Service, South London and Maudsley NHS Foundation Trust, London, UK).

It is rare that such opportunities for cross specialty collaboration occur which makes this an important National and International collaborative effort.

The following points summarise the findings of the review:

• People with SMI and comorbid T2DM receive suboptimal treatment for diabetes
• Treatment with metformin is of proven benefit in this population and is the first line medication for the treatment of T2DM in SMI
• Metformin, and GLP1R- agonists are the only currently available diabetic medications investigated in trials of people with SMI and T2DM studies
• In the management of hyperglycaemia in patients with SMI and T2DM, glucagon-like peptide-1 receptor (GLP1R)-agonist, dipeptidyl peptidase-4 (DPP-4) inhibitor, sulfonylureas, sodium glucose transporter 2 (SGLT2) inhibitors, pioglitazone and insulin may be considered as combination therapy with metformin if the HbA1c target is not achieved after 3 months of metformin monotherapy at maximum tolerated doses
• Agents with a low risk for hypoglycaemia and which may mediate weight loss, such as GLP-1R agonists, DPP-4 inhibitors and the newest SGLT2 inhibitors are preferred choices for second line therapies in SMI.
• Patient engagement in decision making about treatment choices is important to help with adherence and the success of the chosen therapy.
• GLP1-R agonists, exenatide, liraglutide and dulaglutide are associated with improved glycaemic control and weight loss.
• Exenatide and dulaglutide are available as once weekly subcutaneous injections, potentially improving adherence and acceptability
• Consider the use of GLP-1R agonists as a second line treatment for T2DM in SMI, and potentially as a weight loss agent and in preventing the transition from prediabetes to T2DM
• The major concern remains the lack of appropriate treatment intervention for T2DM, and the suboptimal treatment of T2DM in SMI.
• A relevant question is if earlier treatment with metformin or other agents during prediabetes might be beneficial in preventing the transition to T2DM in SMI.
• Prospective observational and implementation studies, and in the use of metformin in combination with GLP-1R agonists, DPP-4 inhibitors, sulphonylureas, pioglitazone and SGLT2 inhibitors are needed to address the evidence gap on the efficacy, tolerability and acceptability of diabetic medications in people with SMI.

The abstract can be read below and the full study is available here.

Pharmacological management of diabetes in severe mental illness: A comprehensive clinical review of efficacy, safety and tolerability

Authors

John Lally, Aonghus O’ Loughlin, Brendon Stubbs, Allys Guerandel, Donal O’ Shea, Fiona Gaughran

Abstract

Introduction: The increased prevalence of Type 2 diabetes mellitus (T2DM) in severe mental illness (SMI) contributes to increased cardiovascular morbidity and reduced life expectancy for people with SMI.
Areas covered: In the present clinical review, we summarize the efficacy, safety and tolerability of selected diabetic pharmacotherapy options in SMI and discuss the quality and strength of evidence.
Expert commentary: General principles for treating T2DM in SMI involve identifying treatments which promote weight loss and which have low or no risk of hypoglycemia. Patient engagement in decision making about treatment choices is an important factor to ensure adherence and successful use of the chosen therapy. The first line therapeutic option for T2DM in SMI for which there is most evidence is metformin. Based on general population data, second line treatment options in combination with metformin to achieve glycated haemoglobin treatment goals include GLP-1R agonists, DPP-4 inhibitors, sulphonylureas, SGLT2 inhibitors, pioglitazone and insulin, with most evidence for the use of GLP-1R agonists in SMI. Alongside efficacy and tolerability, treatment for T2DM in SMI should be considered on a patient-tailored basis.