Dataset Information

Trends in Clinical Characteristics and Prescribing Preferences for SGLT2 Inhibitors and GLP-1 Receptor Agonists, 2013-2018.

ABSTRACT:

Objective

There is a paucity of data evaluating recent changes in clinical and prescriber characteristics of patients initiating sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA).

Research design and methods

U.S.-based administrative claims data (July 2013 to June 2018) were used to identify initiators of SGLT2i and GLP-1RA.

Results

Over 5 years, empagliflozin initiation (as a proportion of SGLT2i) increased by 57.1% (P < 0.001 for trend), while canagliflozin initiation declined by 75.1% (P < 0.001). Empagliflozin was the only agent within SGLT2i with an increase in the proportion of patients with myocardial infarction, stroke, or heart failure (collectively called CVD-HF) (P < 0.001). Liraglutide initiation (as a proportion of total GLP-1RA) declined by 32.1% (P < 0.001), and dulaglutide initiation increased by 34.1% (P < 0.001); the proportion of patients with CVD-HF increased the most in liraglutide initiators (5.1% increase; P < 0.001). Most prescribers were internists or endocrinologists; cardiologist prescribing remained low (<1%).

Conclusions

For SGLT2i, shifts in preference for empagliflozin followed changes in drug labels and guidelines, while for GLP-1RA, other factors such as price or ease of administration may have led to a preference for dulaglutide over liraglutide.

SUBMITTER: Dave CV

PROVIDER: S-EPMC7519473 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Trends in Clinical Characteristics and Prescribing Preferences for SGLT2 Inhibitors and GLP-1 Receptor Agonists, 2013-2018.

Dave Chintan V CV Schneeweiss Sebastian S Wexler Deborah J DJ Brill Gregory G Patorno Elisabetta E

Diabetes care 20200210 4

<h4>Objective</h4>There is a paucity of data evaluating recent changes in clinical and prescriber characteristics of patients initiating sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA).<h4>Research design and methods</h4>U.S.-based administrative claims data (July 2013 to June 2018) were used to identify initiators of SGLT2i and GLP-1RA.<h4>Results</h4>Over 5 years, empagliflozin initiation (as a proportion of SGLT2i) increased by 57.1% ...[more]

PMID: 32041899

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Project description:Aims/hypothesisA precision medicine approach in type 2 diabetes could enhance targeting specific glucose-lowering therapies to individual patients most likely to benefit. We aimed to use the recently developed Bayesian causal forest (BCF) method to develop and validate an individualised treatment selection algorithm for two major type 2 diabetes drug classes, sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA).MethodsWe designed a predictive algorithm using BCF to estimate individual-level conditional average treatment effects for 12-month glycaemic outcome (HbA1c) between SGLT2i and GLP1-RA, based on routine clinical features of 46,394 people with type 2 diabetes in primary care in England (Clinical Practice Research Datalink; 27,319 for model development, 19,075 for hold-out validation), with additional external validation in 2252 people with type 2 diabetes from Scotland (SCI-Diabetes [Tayside & Fife]). Differences in glycaemic outcome with GLP1-RA by sex seen in clinical data were replicated in clinical trial data (HARMONY programme: liraglutide [n=389] and albiglutide [n=1682]). As secondary outcomes, we evaluated the impacts of targeting therapy based on glycaemic response on weight change, tolerability and longer-term risk of new-onset microvascular complications, macrovascular complications and adverse kidney events.ResultsModel development identified marked heterogeneity in glycaemic response, with 4787 (17.5%) of the development cohort having a predicted HbA1c benefit >3 mmol/mol (>0.3%) with SGLT2i over GLP1-RA and 5551 (20.3%) having a predicted HbA1c benefit >3 mmol/mol with GLP1-RA over SGLT2i. Calibration was good in hold-back validation, and external validation in an independent Scottish dataset identified clear differences in glycaemic outcomes between those predicted to benefit from each therapy. Sex, with women markedly more responsive to GLP1-RA, was identified as a major treatment effect modifier in both the UK observational datasets and in clinical trial data: HARMONY-7 liraglutide (GLP1-RA): 4.4 mmol/mol (95% credible interval [95% CrI] 2.2, 6.3) (0.4% [95% CrI 0.2, 0.6]) greater response in women than men. Targeting the two therapies based on predicted glycaemic response was also associated with improvements in short-term tolerability and long-term risk of new-onset microvascular complications.Conclusions/interpretationPrecision medicine approaches can facilitate effective individualised treatment choice between SGLT2i and GLP1-RA therapies, and the use of routinely collected clinical features for treatment selection could support low-cost deployment in many countries.

Project description:BackgroundNo study has compared the cardiovascular outcomes for sodium-glucose cotransporter-2 inhibitors (SGLT2i) head-to-head against other glucose-lowering therapies, including dipeptidyl peptidase 4 inhibitor (DDP4i) or glucagon-like peptide-1 receptor agonist (GLP-1RA)-which also have cardiovascular benefits-in patients with heart failure with reduced (HFrEF) or preserved (HFpEF) ejection fraction.MethodsMedicare fee-for-service data (2013-2019) were used to create four pair-wise comparison cohorts of type 2 diabetes patients with: (1a) HFrEF initiating SGLT2i versus DPP4i; (1b) HFrEF initiating SGLT2i versus GLP-1RA; (2a) HFpEF initiating SGLT2i versus DPP4i; and (2b) HFpEF initiating SGLT2i versus GLP-1RA. The primary outcomes were (1) hospitalization for heart failure (HHF) and (2) myocardial infarction (MI) or stroke hospitalizations. Adjusted hazards ratios (HR) and 95% CIs were estimated using inverse probability of treatment weighting.ResultsAmong HFrEF patients, initiation of SGLT2i versus DPP4i (cohort 1a; n = 13,882) was associated with a lower risk of HHF (adjusted Hazard Ratio [HR (95% confidence interval)], 0.67 (0.63, 0.72) and MI or stroke (HR: 0.86 [0.75, 0.99]), and initiation of SGLT2i versus GLP-1RA (cohort 1b; n = 6951) was associated with lower risk of HHF (HR: 0.86 [0.79, 0.93]), but not MI or stroke (HR: 1.02 [0.85, 1.22]). Among HFpEF patients, initiation of SGLT2i versus DPP4i (cohort 2a; n = 17,493) was associated with lower risk of HHF (HR: 0.65 [0.61, 0.69]) but not MI or stroke (HR: 0.90 [0.79, 1.02]), and initiation of SGLT2i versus GLP-1RA (cohort 2b; n = 9053) was associated with lower risk of HHF (0.89 [0.83, 0.96]), but not MI or stroke (HR: 0.97 [0.83, 1.14]). Results were robust across range of secondary outcomes (e.g., all-cause mortality) and sensitivity analyses.ConclusionsBias from residual confounding cannot be ruled out. Use of SGLT2i was associated with reduced risk of HHF against DPP4i and GLP-1RA, reduced risk of MI or stroke against DPP4i within the HFrEF subgroup, and comparable risk of MI or stroke against GLP-1RA. Notably, the magnitude of cardiovascular benefit conferred by SGLT2i was similar among patients with HFrEF and HFpEF.

Project description:Aims/hypothesisGlucagon-like peptide 1 (GLP-1) agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors are novel drugs which have recently seen rapid uptake in the treatment of type 2 diabetes and obesity. The paucity of data regarding their safety during pregnancy and lactation causes a dilemma for the physician. The aim of the present study was to systematically review all available data on the offspring effects of GLP-1 agonists and SGLT2 inhibitors during pregnancy and lactation.MethodsWe systematically searched PubMed, clinicaltrials.gov, FDA and EMA product information on GLP-1 agonists and SGLT2 inhibitors in pregnancy and lactation from inception up to 19 April 2022 without language restrictions. We approached both the Netherlands Pharmacovigilance Centre Lareb on January 17th 2023 and the Teratology Information Service (TIS) of Switzerland on February 6th 2023. Eligible studies investigating the safety (including congenital anomalies, fetal growth, perinatal demise) in animals or humans, or reporting the degree of transfer of these drugs to the fetus, breast milk or breastfed neonate. Two reviewers independently assessed and selected studies for inclusion and subsequently resolved discrepancies by discussion.ResultsWe included 39 records (n=9 theoretical; based on drug properties, n=7 human; n=23 animal, including 76 human offspring, and an unknown number of animal offspring as these numbers could not be retrieved from the FDA and EMA product information). In animal studies, GLP1-agonists were associated with reduced fetal weight and/or growth, delayed ossification and skeletal variants, usually associated with a reduction in maternal weight gain and decreased food consumption. Exendin-4 (GLP1-agonist) was not transported across the maternal-fetal placental interface. In human studies, exenatide (GLP1-agonist) showed a fetal-to-maternal peptide concentration ratio of ≤ 0.017 in ex vivo human placental perfusion in a single placenta. Liraglutide (GLP1-agonist) showed no significant maternal to fetal transfer at least 3.5 hours after maternal exposure in a human study with one subject. In animal studies, GLP-1 agonists were excreted in breast milk; human data on excretion were not available. In animal studies, SGLT2 inhibitors were generally safe during the first trimester but exposure during postnatal day 21 to 90 in juvenile rats, a period coinciding with the late second and third trimester of human renal development, caused dilatation of the renal pelvis and tubules. Human data consisted of a pharmaceutical database of inadvertent pregnancies during SGLT2 inhibitor use, which found an increase in miscarriages and congenital malformations. In animal studies SGLT2 inhibitors were excreted in breast milk and affected neonatal growth, but human data are not available.Conclusion/interpretationWe found evidence for adverse offspring effects of GLP-1 agonists and SGLT2 inhibitors also in human studies. Our findings broadly support the advice to discontinue GLP-1 agonists and SGLT2 inhibitors during pregnancy and lactation, and also support the ongoing registration of pregnancy outcomes in pharmacological databases since the amount of available data is scarce and mostly limited to animal studies.Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=219877.

Project description:Background: The objective of this review was to assess the risk of lower limb amputation (LLA) in type 2 diabetic patients based on the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) versus dipeptidyl peptidase 4 inhibitors (DPP4i) or glucagon-like peptide-1 receptor agonists (GLP1a). Methods: PubMed, CENTRAL, Scopus, Web of Science, and Embase were referenced for articles published up to 5 February 2023. All types of studies comparing the drugs for LLA risk and reporting hazard ratios (HR) were included. Results: Thirteen studies with 2,095,033 patients were included. Meta-analysis of eight studies comparing SGLT2i with Dipeptidyl peptidase inhibitors (DPPi) showed that there was no difference in the risk of LLA between the two drug groups (HR: 0.98 95% CI: 0.73, 1.31 I2 = 89%). The outcomes were unchanged on sensitivity analysis. Another pooled analysis of six studies found no significant difference in the risk of LLA between SGLT2i and GLP1a users (HR: 1.26; 95% CI: 0.99, 1.60; I2 = 69%). The exclusion of a single study showed an increased risk of LLA with SGLT2i (HR: 1.35; 95% CI: 1.14, 1.60; I2 = 14%). Conclusion: The current updated meta-analysis found no significant difference in the risk of LLA between SGLT2i and DPP4i users. A tendency of increased risk of LLA was noted with SGLT2i as compared to GLP1a. Further studies shall increase the robustness of current findings. Plain language summary Risk of lower limb amputation with SGLT2 inhibitors in comparison with DPP4 inhibitors or GLP-1 agonists among diabetic patients Diabetic foot leading to lower limb amputation (LLA) is a common complication of diabetes mellitus (DM). We compared the risk of LLA in DM patients taking either sodium-glucose cotransporter 2 inhibitors (SGLT2i) or dipeptidyl peptidase 4 inhibitors (DPP4i) / glucagon-like peptide-1 receptor agonists (GLP1a). We searched the available literature for published studies comparing the risk of LLA with SGLT2i versus DPP4i or GLP1a. Individual study data were combined to generate a comprehensive result. We could find 13 studies with data from approximately 2 million patients. After combining the data, we noted no difference in the risk of LLA between patients using SGLT2i versus DPPi or GLP1a. Nevertheless, when data from a single study was removed from the combined analysis, we noted an increased risk of LLA with SGLT2i in comparison with GLP1a users. To conclude, our study, which is a comprehensive literature review, found that there is no difference in the risk of LLA between SGLT2i and DPP4i users. A tendency of increased risk of LLA was seen with SGLT2i as compared to GLP1a, which requires further research.

Dataset Information

Trends in Clinical Characteristics and Prescribing Preferences for SGLT2 Inhibitors and GLP-1 Receptor Agonists, 2013-2018.

Objective

Research design and methods

Results

Conclusions

Publications

Trends in Clinical Characteristics and Prescribing Preferences for SGLT2 Inhibitors and GLP-1 Receptor Agonists, 2013-2018.

Similar Datasets

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