Sodium-Glucose Cotransporter-2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes: Protocol for a Kidney End Points Real-world Study (COMBi-KID Study)

Michael Feher; William Hinton; Anna Forbes; Neil Munro; Mark Joy; David Wheeler; Simon de Lusignan

doi:10.2196/34206

Sodium-Glucose Cotransporter-2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes: Protocol for a Kidney End Points Real-world Study (COMBi-KID Study)

JMIR Res Protoc. 2022 Jul 19;11(7):e34206. doi: 10.2196/34206.

Authors

Michael Feher^#¹, William Hinton^#¹, Anna Forbes¹, Neil Munro^#², Mark Joy¹, David Wheeler^#³, Simon de Lusignan^#¹

Affiliations

¹ Clinical Informatics and Health Outcomes Research Group, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
² Clinical Informatics, University of Surrey, Guildford, United Kingdom.
³ Department of Renal Medicine, University College London, London, United Kingdom.

^# Contributed equally.

PMID: 35852840
PMCID: PMC9346560
DOI: 10.2196/34206

Abstract

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are both considered to be part of standard care in the management of glycemia in type 2 diabetes. Recent trial evidence has indicated benefits on primary kidney end points for individual drugs within each medication class. Despite the potential benefits of combining SGLT2is and GLP-1RAs for glycemia management, according to national and international guideline recommendations, there is currently limited data on kidney end points for this drug combination.

Objective: The aims of the study are to assess the real-world effects of combination SGLT2i and GLP-1RA therapies for diabetes management on kidney end points, glycemic control, and weight in people with type 2 diabetes who are being treated with renin-angiotensin system blockade medication.

Methods: This retrospective cohort study will use the electronic health records of people with type 2 diabetes that are registered with general practices covering over 15 million people in England and Wales and are included in the Oxford-Royal College of General Practitioners Research and Surveillance Centre network. A propensity score-matched cohort of prevalent new users of SGLT2is and GLP-1RAs and those who have been prescribed SGLT2is and GLP-1RAs in combination will be identified. They will be matched based on drug histories, comorbidities, and demographics. A repeated-measures, multilevel, linear regression analysis will be performed to compare the mean change (from baseline) in estimated glomerular filtration rate at 12 and 24 months between those who switched to combined therapy and those continuing monotherapy with an SGLT2i or GLP-1RA. The secondary end points will be albuminuria, serum creatinine level, glycated hemoglobin level, and BMI. These will also be assessed for change at the 12- and 24-month follow-ups.

Results: The study is due to commence in March 2022 and is expected to be complete by September 2022.

Conclusions: Our study will be the first to assess the impact of combination SGLT2i and GLP-1RA therapy in type 2 diabetes on primary kidney end points from a real-world perspective.

International registered report identifier (irrid): PRR1-10.2196/34206.

Keywords: electronic health records; glucagon-like peptide-1 receptor agonist; kidney; renal; sodium-glucose cotransporter-2 inhibitor; type 2 diabetes.

©Michael Feher, William Hinton, Anna Forbes, Neil Munro, Mark Joy, David Wheeler, Simon de Lusignan. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 19.07.2022.