Although a multitude of treatment options exist for management of blood sugar and body weight in people with diabetes (persistently high blood sugar), little is known about potential effective treatments for people with both diabetes and chronic kidney disease – especially with more severe kidney impairment, where few treatment options exist. This lack of knowledge could lead to a general reluctance among treating physicians to prescribe potentially effective treatments in these patients.
Therefore, the aim of this study is to investigate the effectiveness of different diabetes treatment alternatives in people with diabetes and impaired kidney function in lowering blood sugar and reducing body weight.
This evidence will serve to guide treating physicians as well as people with both diabetes and impaired kidneys in the choice of effective treatments to manage their diabetes.
There is limited evidence concerning effective and safe therapies for type-2 diabetes (T2D) management in people with chronic kidney disease (CKD). While guidelines exist for some glucose lowering agents (GLA), evidence is lacking for other potential safe and effective treatments. The lack of knowledge may induce therapeutic inertia with treating physicians, with resulting adverse consequences for patients receiving suboptimal care.
While the limited evidence supports safety and tolerability of glucagon like peptide-1 receptor agonists (GLP-1) in people with CKD, studies are lacking on the comparative effectiveness to other GLAs.
The objective of this study is, through an active comparator new user design, to determine the comparative effectiveness of GLP-1 vs. GLA alternatives in T2D patients with CKD on 6-months change in haemoglobin A1c (HbA1c) and body weight (BW). More specifically comparing:
A) GLP-1 vs. sodium/glucose cotransporter-2 inhibitors in people with T2D & eGFR 30 to 60 mL/min/1.73m2.
B) GLP-1 vs. dipeptidyl peptidase 4 inhibitors in people with T2D & eGFR <60 mL/min/1.73m2.
Adult new users of study GLAs diagnosed with T2D and an eGFR <60 within one year prior to initiation of GLA will be identified in CPRD Aurum between 2007 and 2022 and included for analysis if they also fulfil the following; minimum 1 year observation time prior to initiation of study GLA, have data on HbA1c and/or BW within three months prior to and within 6 months following initiation of study GLA.
Mixed models with repeated measures using baseline and all available follow-up measurements will be used to estimate change in HbA1c and BW. HbA1c will be modelled using restricted cubic splines. Random subject coefficients for intercept and slope with respect to time will be included. Propensity score will be used to account for confounding through inverse probability of treatment weights or matching depending on the data.
Primary outcomes: 6 months changes in HbA1c (%-point); 6 months change in body weight (in kilo grams and %-change).
Applied codes are listed in Appendix 2.
Secondary outcomes: the proportion of people with an HbA1c <7% at 6 months, among those above that threshold at initiation of study drugs; a body weight reduction of >5% at 6 months among people with overweight or obesity at initiation of study drug.
Alice Clark - Chief Investigator - Novo Nordisk A/S
Alice Clark - Corresponding Applicant - Novo Nordisk A/S
Anders Boeck Jensen - Collaborator - Novo Nordisk A/S
Katherine Tuttle - Collaborator - University Of Washington
Kathrine Valentini Jensen - Collaborator - Novo Nordisk A/S
Nicolas Belmar Nazal - Collaborator - Novo Nordisk A/S
Paola Fioretto - Collaborator - University of Padova
peter rossing - Collaborator - University of Copenhagen