Type 2 diabetes mellitus (T2DM) is a lifelong condition where patients are not able to control their blood sugar levels. Patients with T2DM can control their blood sugar with effective treatment and usually start receiving a single drug. However, if patients are unable to control their blood sugar levels and their average blood sugar measurement (referred to as HbA1c) goes above a certain level (7.5% [58mmol/mol]), then patients may be offered a second drug and national treatment guidelines recommend drugs belonging to one of three drug classes:
- Sulphonylureas (SU's);
- Dipeptidyl peptidase-4 inhibitors (DPP4i);
- Sodium-glucose cotransporter-2 inhibitors (SGLT2i)
These medications have similar effects in clinical trials, but their effect in the real-world is less well understood. Additionally, while treatment guidelines recommend a second drug be given to patients that are unable to control their blood sugar levels below (7.5% [58mmol/mol]), it is not clear when this occurs in clinical practice
This study aims to evaluate whether the impact of adding a second drug to a patient's treatment regimen in clinical practice varies according to the patient's HbA1c level at the start of treatment. In addition, the study will evaluate the impact of each class of drug on patients' blood sugar levels and outcomes such as changes in body weight, stopping rates and diabetes-related complications. A better understanding of how patients' blood sugar levels at the start of a new treatment regimen may lead to better management of patients with T2DM and improved patient outcomes.
Patient-level data will be extracted from CRPD to retrospectively analyse a cohort of T2DM patients (>/=18 years of age) who were prescribed both metformin and one of three medications between 01-01-2002 and 31-12-2017:
- SU's;
- DPP4i's;
- or SGLT2i's.
HbA1c and other key outcomes including body weight and discontinuation/treatment intensification rates between date of dual therapy initiation and 6- and 12- months post will be compared by class of drug to understand the real-world effectiveness of the different treatment options available. Multivariable statistical analyses will test for statistically significant differences between drug class to determine if the hypothesis, that there is no difference between drug class holds true.
Secondary outcomes within the study have been derived to understand whether per drug classification, there exists notable differences between both medication usage and toxicity-based event counts. The medication possession ratio (MPR) will be used to calculate adherence to understand its impact on effectiveness. Secondary outcomes will be tested for significant difference.
The following health outcomes will be derived and analysed:
6- and 12- month HbA1c change from baseline;
6- and 12- month body weight change from baseline;
Discontinuation rates (treatment switch/cessation) at 6- and 12-months post-baseline;
Treatment intensification (treatment switch/addition) rates at 6- and 12- months post-baseline;
Mean across medications
Medication persistence
Genital/urinary tract infection rates;
Hypoglycaemic episode counts;
Rates of the following adverse events: hypoglycaemia, bacterial genitourinary infection, fungal genital infection, fractures, lower limb amputation, pancreatitis, ketosis/diabetic ketoacidosis (DKA), heart failure and cardiovascular events (acute coronary syndrome (ACS), transient ischemic attack (TIA), stroke, peripheral vascular disease (PVD)).
Phil McEwan - Chief Investigator - Health Economics & Outcomes Research Ltd ( HEOR Ltd )
Michael Hurst - Corresponding Applicant - Health Economics & Outcomes Research Ltd ( HEOR Ltd )
David Strain - Collaborator - University of Exeter
Marc Evans - Collaborator - Llandough Hospital
Minesh Unadkat - Collaborator - Takeda Development Center Americas, Inc.
Simon Meadowcroft - Collaborator - Takeda Development Center Americas, Inc.
Thomas Mason - Collaborator - Health Economics & Outcomes Research Ltd ( HEOR Ltd )