Enhancing evidence-based guidelines using trial emulation in electronic health records: Real-world effects of empagliflozin in people with type 2 diabetes
Abstract
ABSTRACT:
Background: There is growing interest in widening the use of sodium-glucose co-transporter-2 inhibitors (SGLT2i) to all people with type 2 diabetes mellitus (T2DM). However, pivotal randomised controlled trials (RCTs) evaluated these drugs only in highly selected populations, often lacking generalisability to real-world populations. Understanding the effects of SGLT2i in populations, where RCT evidence may be lacking is essential to help inform guideline development. To address this, we estimated the effect of empagliflozin in a real-world users, many of whom would not have been eligible for the pivotal EMPA-REG RCT.
Methods: We designed a trial emulation in UK primary care data, based on the EMPA-REG RCT, to assess the effect of empagliflozin in a more clinically relevant population. Adults with T2DM initiating empagliflozin (intervention) or dipeptidyl peptidase-4 inhibitors (active control) between 1 Jan 2014–31 Dec 2022 were included. Eligibility was extended to both RCT-eligible and RCT-ineligible individuals. The effect of empagliflozin on all-cause mortality was estimated using an adjusted Cox proportional hazards model, with stratified analyses by RCT eligibility.
Findings: The majority of people prescribed empagliflozin would not have met the EMPA-REG RCT eligibility criteria (11011/13239, 83.2% RCT-ineligible). During follow-up, all-cause mortality occurred in 551/13239 (4.2%) of the empagliflozin group and 6589/49264 (13.4%) of the active control group…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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