Dataset Information

Incidence and Predictors of Primary Nonadherence to Sodium Glucose Co-transporter 2 Inhibitors and Glucagon-Like Peptide 1 Agonists in a Large Integrated Healthcare System.

ABSTRACT:

Background

Newer glucose-lowering drugs, including sodium glucose co-transporter 2 inhibitors (SGLT2i) and GLP-1 agonists, have a key role in the pharmacologic management of type 2 diabetes. No studies have measured primary nonadherence for these two drug classes, defined as when a medication is prescribed for a patient but ultimately not dispensed to them.

Objective

To describe the incidence and predictors of primary nonadherence to SGLT2i (canagliflozin, empagliflozin) or GLP-1 agonists (dulaglutide, liraglutide, semaglutide) using a dataset that links electronic prescribing with health insurance claims.

Design and participants

A retrospective cohort design using data of adult patients from a large health system who had at least one prescription order for a SGLT2i or GLP-1 agonist between 2012 and 2019. We used mixed-effects multivariable logistic regression to determine associations between sociodemographic, clinical, and provider variables and primary nonadherence.

Main measures

Primary medication nonadherence, defined as no dispensed claim within 30 days of an electronic prescription order for any drug within each medication class.

Key results

The cohort included 5146 patients newly prescribed a SGLT2i or GLP-1 agonist. The overall incidence of 30-day primary medication nonadherence was 31.8% (1637/5146). This incidence rate was 29.8% (n = 726) and 33.6% (n = 911) among those initiating a GLP-1 agonist and SGLT2i, respectively. Age ≥ 65 (aOR 1.37 (95% CI 1.09 to 1.72)), Black race vs White (aOR 1.29 (95% CI 1.02 to 1.62)), diabetic nephropathy (aOR 1.31 (95% CI 1.02 to 1.68)), and hyperlipidemia (aOR 1.18 (95% CI 1.01 to 1.39)) were associated with a higher odds of primary nonadherence. Female sex (aOR 0.86 (95% CI 0.75 to 0.99)), peripheral artery disease (aOR 0.73 (95% CI 0.56 to 0.94)), and having the index prescription ordered by an endocrinologist vs a primary care provider (aOR 0.76 (95% CI 0.61 to 0.95)) were associated with lower odds of primary nonadherence.

Conclusions

One third of patients prescribed SGLT2i or GLP-1 agonists in this sample did not fill their prescription within 30 days. Black race, male sex, older age, having greater baseline comorbidities, and having a primary care provider vs endocrinologist prescribe the index drug were associated with higher odds of primary nonadherence. Interventions targeting medication adherence for these newer drugs must consider primary nonadherence as a barrier to optimal clinical care.

SUBMITTER: Luo J

PROVIDER: S-EPMC9585108 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Incidence and Predictors of Primary Nonadherence to Sodium Glucose Co-transporter 2 Inhibitors and Glucagon-Like Peptide 1 Agonists in a Large Integrated Healthcare System.

Luo Jing J Feldman Robert R Rothenberger Scott S Korytkowski Mary M Fischer Michael A MA Gellad Walid F WF

Journal of general internal medicine 20220119 14

<h4>Background</h4>Newer glucose-lowering drugs, including sodium glucose co-transporter 2 inhibitors (SGLT2i) and GLP-1 agonists, have a key role in the pharmacologic management of type 2 diabetes. No studies have measured primary nonadherence for these two drug classes, defined as when a medication is prescribed for a patient but ultimately not dispensed to them.<h4>Objective</h4>To describe the incidence and predictors of primary nonadherence to SGLT2i (canagliflozin, empagliflozin) or GLP-1 ...[more]

PMID: 35048301

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Project description:AimsMost trials leading to the approval of glucagon-like peptide receptor agonists (GLP-1RAs) and sodium-glucose co-transporter-2 inhibitors (SGLT2is) were primarily designed to confirm their non-inferiority to placebo (commonly using an upper 95% confidence limit threshold of 1.3) and, if confirmed, superiority (threshold 1): this asymmetry of margins (1 vs. 1.3) favours the active intervention. We aimed to quantify the probability of clinical superiority of the active treatment by applying the same threshold used to claim non-inferiority.Materials and methodsWe searched PubMed and Cochrane CENTRAL for cardiorenal outcome trials in subjects with type 2 diabetes published before 5 December 2021, to reconstruct from Kaplan-Meier plots individual-level data for the primary outcome or all-cause mortality. We calculated Bayesian posterior densities to obtain the probability for a treatment effect (hazard ratio) <0.769, which is symmetric to the 1.3 threshold (i.e. its reciprocal 1/1.3), emulating a scenario where the active treatment is placebo and placebo is the active treatment.ResultsWe extracted data from 27 Kaplan-Meier plots (18 for the primary outcome, nine for mortality). Probabilities of clinical superiority to placebo varied significantly: for GLP-1RAs, from a minimum of 0% to a maximum of 69% for the primary outcome and from 0% to 8% for mortality; corresponding estimates for SGLT2is were 0% to 96% and 0% to 93%. Probabilities were on average greater for SGLT2is, particularly in trials investigating kidney or heart failure outcomes.ConclusionsThe probability of clinical superiority to placebo varies widely across trials previously reported as showing superiority of GLP-1RAs or SGLT2is compared with placebo. These results showed within- and between-class differences, highlight the drawbacks of a binary interpretation of the results, particularly in the context of the current designs of non-inferiority trials, and have implications for decision makers and future clinical recommendations.

Project description:BackgroundNumerous studies have investigated the potential association of sodium-glucose co-transporter-2 inhibitors (SGLT2-Is) with an increased risk of lower limb amputations (LLAs), but have produced conflicting results. Particularly studies comparing SGLT2-Is to glucagon-like peptide-1 receptor agonists (GLP1-RAs) seem to find a higher LLA risk with SGLT2-I use. This raises the question whether the results are driven by a protective GLP1-RA-effect rather than a harmful SGLT2-I-effect. GLP1-RAs could promote wound healing and therefore reduce the risk of LLAs, but the associations between both drug classes and LLA remain uncertain. Therefore, the aim of the current study was to investigate the risk of LLA and diabetic foot ulcer (DFU) with SGLT2-I use and GLP1-RA use versus sulfonylurea use.MethodsA retrospective population-based cohort study was conducted using data from the Danish National Health Service (2013-2018). The study population (N = 74,475) consisted of type 2 diabetes patients aged 18 + who received a first ever prescription of an SGLT2-I, GLP1-RA or sulfonylurea. The date of the first prescription defined the start of follow-up. Time-varying Cox proportional hazards models estimated the hazard ratios (HRs) of LLA and DFU with current SGLT2-I use and GLP1-RA use versus current SU use. The models were adjusted for age, sex, socio-economic variables, comorbidities and concomitant drug use.ResultsCurrent SGLT2-I use was not associated with a higher risk of LLA versus sulfonylureas {adjusted HR 1.10 [95% confidence interval (CI) 0.71-1.70]}. Current GLP1-RA use, on the other hand, was associated with a lower risk of LLA [adjusted HR 0.57 (95%CI 0.39-0.84)] compared to sulfonylureas. The risk of DFU was similar to that with sulfonylureas with both exposures of interest.ConclusionSGLT2-I use was not associated with a higher risk of LLA, but GLP1-RAs with a lower risk of LLA. Previous studies reporting a higher risk of LLA with SGLT2-I use compared to GLP1-RA use might have been looking at a protective GLP1-RA effect, rather than a harmful SGLT2-I effect.

Dataset Information

Incidence and Predictors of Primary Nonadherence to Sodium Glucose Co-transporter 2 Inhibitors and Glucagon-Like Peptide 1 Agonists in a Large Integrated Healthcare System.

Background

Objective

Design and participants

Main measures

Key results

Conclusions

Publications

Incidence and Predictors of Primary Nonadherence to Sodium Glucose Co-transporter 2 Inhibitors and Glucagon-Like Peptide 1 Agonists in a Large Integrated Healthcare System.

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