A real-world study comparing the effectiveness and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter 2 inhibitors (SGLT-2is) in patients with type 2 diabetes

Date of Approval: 
2019-08-28 00:00:00
Lay Summary: 
Type 2 diabetes is an increasingly common condition that has serious long-term effects. This condition leads to high blood-sugar levels, which can lead to complications such as stroke and heart failure. Due to the many risk factors and health complications that can happen, managing and reducing blood-sugar levels in people with type 2 diabetes is highly important. There are many medication options available to reduce blood-sugar levels in people with type 2 diabetes, with new treatments continuously being developed. Two newly developed treatments for type 2 diabetes include glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter 2 inhibitors (SGLT-2is). Research has suggested that, as well as reducing blood sugar levels, both GLP-1RAs and SGLT-2is have additional benefits, such as reducing body weight and the risk of heart problems. Furthermore, patients with type 2 diabetes often require multiple diabetes medications to keep their blood sugar levels down. However, although GLP-1RAs or SGLT-2is are recommended as an optional treatment addition when single drug therapy is not effective, it is currently not known which of these two treatment classes are preferable in the management of type 2 diabetes. Thus, this study aims to compare patients’ who are prescribed GLP-1RAs with patients’ who are prescribed SGLT-2is for effectiveness and safety outcomes. This study will provide important information to help with clinical decision making in practice.
Technical Summary: 
New drugs for the management of hyperglycaemia in type 2 diabetes are continuously being developed. In recent years, advancements have been made in two classes of glucose-lowering drugs: glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter 2 inhibitors (SGLT-2is). As well as reducing blood sugar levels, evidence shows that these classes of drugs also improve cardiovascular and renal outcomes. However, much of this evidence is based on randomised controlled trials and does not fully represent patients in the real-world clinical setting. Although guidelines suggest when GLP-1RAs and SGLT-2is should be administered, current research lacks clear guidance as to which specific drug should be used first. Available systematic reviews and network meta-analysis have compared effectiveness of these drugs within these two classes, however, the benefit–risk profile between the two classes and which drug should be preferred remains unclear. This study will use routinely collected data from the Clinical Practice Research Datalink to initially describe demographic and medical profiles of patients taking GLP-1RAs or SGLT-2is. This will be followed by a risk-assessment of heart failure hospitalisation, cardiovascular events and mortality between the two drug classes. Intermediate cardiometabolic outcomes (i.e. glucose lowering, body weight, blood pressure and cholesterol levels) and adverse events will also be assessed.
Health Outcomes to be Measured: 
Effectiveness outcomes: Primary (Cardiovascular) outcomes - hospitalisation for heart failure, all-cause mortality, 3-point MACE (major adverse cardiovascular events): stroke, myocardial infarction and cardiovascular mortality. Secondary (Cardiometabolic) outcomes - change in: glycated haemoglobin (HbA1c; %, mmol/mol), body weight (kg), total-cholesterol (mmol/l), HDL-cholesterol (mmol/l), LDL-cholesterol (mmol/l), triglycerides (mmol/l), systolic blood pressure (mm/Hg), diastolic blood pressure (mm/Hg) and heart rate (bpm). Safety outcomes - hypoglycaemia, amputations, bone fractures, pancreatitis, cancer, genital infection, urinary tract infection, injection site reactions, abdominal pain and diabetic ketoacidosis.
Application Number: 

Laura Gray - Chief Investigator - University of Leicester
Humaira Hussein - Corresponding Applicant - University of Leicester
Francesco Zaccardi - Collaborator - University of Leicester
Kamlesh Khunti - Collaborator - University of Leicester
Melanie Davies - Collaborator - University of Leicester

HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation