Approximately 3 million people have been diagnosed with type 2 diabetes (T2D) in the United Kingdom (UK). T2D is a condition that causes high levels of sugar (glucose) in the blood, and accounts for about one in ten pounds that the NHS spends.
Guidelines recommend that most T2D patients start treatment with a drug called metformin. Patients can then be prescribed additional drugs if required, such as sulfonylurea, dipeptidyl peptidase-4 inhibitor, or sodium-glucose cotransporter-2 inhibitor. There is wide variation across the UK in which of these drugs are prescribed. This treatment choice should be personalised according to patient characteristics such as age or weight but there is little evidence to inform this choice.
This study aims to evaluate the relative effectiveness of alternative drugs available for T2D treatment, and provide evidence to help target treatments for individual patients.
This study will examine the variation in treatment choices across Clinical Commissioning Groups seen in CPRD data. We will compare the outcomes experienced by different groups of people with T2DM who have taken the alternative drugs for first stage intensification. Our study design will recognise that patients receiving these alternative treatments may differ from one other. The study will provide accurate estimates of how effective these alternative treatments are for individual patients, according for example to their age or initial weight. We will report the impact of alternative first stage intensification treatments on short-term outcomes such as cholesterol levels, and long-term outcomes like amputation rates.
Background: Clinical guidelines for T2DM require evidence to help personalise treatment choice. For people who require an antidiabetic drug as an add on to metformin, there is controversy about whether newer, more costly classes of drug (dipeptidyl peptidase-4 inhibitors (DPP4is) or sodium-glucose cotransporter-2 inhibitor (SGLTis)) reduce the risk of long-term complications versus sulfonylureas (SUs).
Aims: This study aims to evaluate the relative effectiveness of alternative oral drug regimens for 1st stage treatment intensification for people with T2DM, and provide the evidence required to target treatments for individual patients.
Objectives:
1. To assess short-term relative effectiveness according to individual risk factor profiles.
2. To calibrate and extend an existing microsimulation model for patients with T2DM in the UK (RAPIDS-UK).
3. To estimate long-term effectiveness according to individual risk factor profiles, and project the NHS budget impact of personalising drug choice.
Methods: This study will use an advanced Instrumental Variable (IV) method and adapt a microsimulation model to the UK setting to provide unbiased estimates of relative effectiveness according to the individual patients risk profile. The study will apply this IV design to UK primary and secondary care data from 2011-2019.
The target population is people with T2DM prescribed SU, DPP4i or SGLT2i for 1st-stage intensification. Baseline characteristics, biomarker levels, concomitant medications, and long-term outcomes (micro- and macro- vascular complications, mortality and related hospital admissions) will be used to estimate the short-term effectiveness of the different drugs on haemoglobin A1c (HbA1c) according to individual patients risk profiles (Obj 1).
We will extend a microsimulation model to calibrate long-term outcomes (follow-up to 9 years) according to those observed in primary care (Obj 2). We will predict long-term effectiveness of the treatment alternatives according to individual-level risk profiles (Obj 3), and project the budget impact of personalising the choice of 1st-stage intensification therapy.
The primary outcome for objective 1 will be HbA1c at 12 months after the onset of first-stage treatment intensification. Secondary outcomes will include: HDL, LDL, total cholesterol, BMI, SBP, DBP and eGFR also at 12 months follow-up. The secondary analyses will use data on repeated measures for each biomarker for the maximum available follow-up (up to five years). We will report the number of inpatient hospital admissions where one of the long-term outcomes of interest are reported for up to five years. We will report adherence according to defined daily dose (DDD), the time to cessation of first-line intensification, and the time to prescription of subsequent antidiabetic therapy including treatment switching for example a SGLTi for a patient previously receiving a DPP4i.
Richard Grieve - Chief Investigator - London School of Hygiene & Tropical Medicine ( LSHTM )
Patrick Bidulka - Corresponding Applicant - London School of Hygiene & Tropical Medicine ( LSHTM )
Amanda Adler - Collaborator - Cambridge University Hospitals
Andrew Briggs - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Anirban Basu - Collaborator - University Of Washington
David Lugo Palacios - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
David McAllister - Collaborator - University of Glasgow
David Whitney - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Dorothea Nitsch - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Elaine Butterly - Collaborator - University of Glasgow
Ian Douglas - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Ignacio Leiva-Escobar - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
James Burns - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Kamlesh Khunti - Collaborator - University of Leicester
Karla DiazOrdaz - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Liam Smeeth - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Orlagh Carroll - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Paul Charlton - Collaborator - National Institute for Health Research - NIHR London Office
Qiaoling Liu - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Richard Silverwood - Collaborator - University College London ( UCL )
Stephen O'Neill - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Tsz Lun Ernest Wong - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Viola Spahiu - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Ying-Ting Chiang - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
David Ryan - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Ruth Keogh - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Stephen O'Neill - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;CCG Pseudonyms