Lower risks of new-onset acute pancreatitis and pancreatic cancer in sodium glucose cotransporter 2 (SGLT2) inhibitors compared to dipeptidyl peptidase-4 (DPP4) inhibitors: A propensity score-matched study with competing risk analysis

Chou, Oscar Hou In; Zhou, Jiandong; MBBChir, Jonathan V Mui; Satti, Danish Iltaf; Chung, Cheuk To; Lee, Teddy TaiLoy; Lee, Sharen; Dee, Edward Christopher; MBBChir, Kenrick Ng; Cheung, Bernard Man Yung; Jing, Fengshi; Tse, Gary

doi:10.1016/j.deman.2022.100115

Cited by 9 publications

(6 citation statements)

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“…This system has been used extensively by our teams and other research teams in Hong Kong, including diabetes and medication research. [11, 12] The system contains data on disease diagnosis, laboratory results, past comorbidities, clinical characteristics, and medication prescriptions. T2DM patients who were administered with GLP1a in centres under the HA, between 1 st January 2015, to 31 st December 2020, were included.…”

Section: Methodsmentioning

confidence: 99%

Compare SGLT2I versus non-SGLT2I users in type-2 diabetic mellitus patients on GLP-1 receptor agonist: A population-based and machine learning causal inference analysis

Luo,

Chou,

et al. 2023

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BackgroundBoth sodium-glucose cotransporter-2 (SGLT2) inhibitors and GLP-1 receptor agonists (GLP1a) demonstrated benefits against cardiovascular diseases in type 2 diabetes (T2D). However, the effects of SGLT2I amongst patients already on GLP1a users remain unknown.ObjectiveThis real-world study compared the risks of cardiovascular diseases with and without exposure to SGLT2I amongst GLP1a users.MethodsThis was a retrospective population-based cohort study of patients with type-2 diabetes mellitus (T2DM) on GLP1a between 1st January 2015 and 31st December 2020 using a territory-wide registry from Hong Kong. The primary outcomes were new-onset myocardial infarction, atrial fibrillation, heart failure, and stroke/transient ischaemic attack (TIA). The secondary outcome was all-cause mortality. Propensity score matching (1:2 ratio) using the nearest neighbour search was performed. Multivariable Cox regression was used to identify significant associations. The machine learning causal inference analysis was used to estimate the treatment effect.ResultsThis cohort included 2526 T2DM patients on GLP1a (median age: 52.5 years old [SD: 10.9]; 57.34 % males). The SGLT2I users and non-SGLT2I users consisted of 1968 patients and 558 patients, respectively. After matching, non-SGLT2I users were associated with high risks of myocardial infarction (Hazard ratio [HR]: 2.91; 95% Confidence Interval [CI]: 1.30-6.59) and heart failure (HR: 2.49; 95% CI: 1.22-5.08) compared to non-SGLT2I users after adjusting for demographics, comorbidities, medications, renal function, and glycaemic tests. However, non-SGLT2I users were not associated with the risks of atrial fibrillation (HR: 1.52; 95% CI: 0.65-3.53) and stroke/TIA (HR: 1.72; 95% CI: 0.70-4.24). The results remained consistent in the competing risk and the sensitivity analyses.ConclusionsSGLT2I non-users was associated with higher risks of myocardial infarction and heart failure when compared to SGLT2I users after adjustments amongst T2DM patients on GLP1a. The result remained consistent in the machine learning causal inference analysis.Graphical abstract

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Section: Methodsmentioning

confidence: 99%

Compare SGLT2I versus non-SGLT2I users in type-2 diabetic mellitus patients on GLP-1 receptor agonist: A population-based and machine learning causal inference analysis

Luo,

Chou,

et al. 2023

Preprint

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“…The system contains data on disease diagnosis, laboratory results, past comorbidities, clinical characteristics, and medication prescriptions. The system has been used by our Hong Kong research team to perform comparative studies [9, 15, 16]. T2DM patients who were administered with SGLT2I or DPP4I in centres under the Hong Kong HA, between January 1st, 2015, to December 31st, 2020, were included.…”

Section: Methodsmentioning

confidence: 99%

New-onset prostate cancer in type 2 diabetes mellitus exposed to the SGLT2I, DPP4I and GLP1a: A population-based cohort study

Chou,

Lu,

Chung

et al. 2023

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BackgroundSodium-glucose cotransporter 2 inhibitors (SGLT2I) have been suggested to reduce new-onset cancer amongst type-2 diabetes mellitus (T2DM) patients.ObjectiveThis real-world study aims to compare the risks of prostate cancer between SGLT2I and dipeptidyl peptidase-4 inhibitors (DPP4I) amongst T2DM patients.Design, setting and participantsThis was a retrospective population-based cohort study of prospectively recorded data on type-2 diabetes mellitus (T2DM) male patients prescribed either SGLT2I or DPP4I between January 1st2015 and December 31st2020 from Hong Kong.MethodsThe primary outcome was new-onset prostate cancer. The secondary outcomes included cancer-related mortality and all-cause mortality. Propensity score matching (1:1 ratio) using the nearest neighbour search was performed and multivariable Cox regression was applied to compare the risk. A three-arm sensitivity analysis including the glucagon-like peptide-1 receptor agonist (GLP1a) cohort was conducted.ResultsThis study included 42129 male T2DM patients (median age: 61.0 years old [SD: 12.2]; SGLT2I: n=17120; DPP4I: n=25009). After matching, the number of prostate cancers was significantly lower in SGLT2I users (n = 60) than in DPP4I (n = 102). SGLT2I use was associated with lower prostate cancer risks (HR: 0.45; 95% CI: 0.30-0.70) after adjustments than DPP4I. The results remained consistent in the sensitivity analysis. SGLT2I reduced the risks of prostate cancer prominently amongst patients who were older (age >65), patients with 2ndand 3rdquartile of HbA1c, concurrent metformin uses, and concurrent sulphonylurea uses. SGLT2I was associated with higher risks of prostate cancer amongst sulphonylurea non-users.ConclusionThe real-world study demonstrated SGLT2I was associated with lower risks of new-onset prostate cancer after matching and adjustments compared to DPP4I. This result warrants further prospective studies.Graphical abstract

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“…The system has been used by local teams in Hong Kong to conduct comparative studies. [13][14][15] The exclusion criteria of the study involved patients: 1) With prior NPC or H&N cancer 2) Without complete demographics 3) Under 18 years old (Figure 1). This study employed an as-treat approach, including the censoring of patients at the discontinuation of treatment or switching between the comparison medications.…”

Section: Study Design and Populationmentioning

confidence: 99%

Nasopharyngeal Carcinoma and Head and Neck Cancer in Patients with Type-2 Diabetes Mellitus receiving SGLT2I, DPP4I or GLP1a: A population-based cohort study

Li,

Chou,

Mak

et al. 2024

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Introduction: Nasopharyngeal carcinoma (NPC) remains endemic in Asian regions, which risk factors were distinct from other head and neck (H&N) cancers. Anti-diabetic drugs has been proposed to reduce the risk of NPC. The associations between sodium glucose cotransporter 2 inhibitors (SGLT2I) versus dipeptidyl peptidase-4 inhibitors (DPP4I) and the risks of NPC and H&N cancer amongst type-2 diabetes mellitus (T2DM) patients remains unknown. Method: This was a retrospective population-based cohort study including T2DM patients treated with either SGLT2I or DPP4I between 1st January 2015 and 31st December 2019 in Hong Kong. The primary outcome was new-onset NPC and other H&N cancer. The secondary outcome was cancer-related mortality. Propensity score matching (1:1 ratio) was performed using the nearest neighbour search. Multivariable Cox regression was applied to identify significant predictors. Results: This cohort included 75,884 patients with T2DM, amongst whom 28,778 patients were on SGLT2I and 47,106 patients were on DPP4I. After matching (57556 patients), 106 patients developed NPC (0.18%), and 50 patients developed H&N cancer (0.08%). Compared to DPP4I, SGLT2I was associated with significantly lower risks of NPC (Hazard ratio [HR]: 0.41; 95% Confidence interval [CI]: 0.21-0.81) but not H&N cancer (HR: 1.00; 95% CI: 0.26-3.92) after adjustments. The result remained significant regardless of demographics and obesity. The association remained consistent in different risk models, matching approaches, and the sensitivity analysis. Conclusion: This study provides real-world evidence that SGLT2I was associated with lower risks of NPC, but not H&N cancer compared to DPP4I after adjustments amongst T2DM patients.

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Lower risks of new-onset acute pancreatitis and pancreatic cancer in sodium glucose cotransporter 2 (SGLT2) inhibitors compared to dipeptidyl peptidase-4 (DPP4) inhibitors: A propensity score-matched study with competing risk analysis

Cited by 9 publications

References 43 publications

Compare SGLT2I versus non-SGLT2I users in type-2 diabetic mellitus patients on GLP-1 receptor agonist: A population-based and machine learning causal inference analysis

Compare SGLT2I versus non-SGLT2I users in type-2 diabetic mellitus patients on GLP-1 receptor agonist: A population-based and machine learning causal inference analysis

New-onset prostate cancer in type 2 diabetes mellitus exposed to the SGLT2I, DPP4I and GLP1a: A population-based cohort study

Nasopharyngeal Carcinoma and Head and Neck Cancer in Patients with Type-2 Diabetes Mellitus receiving SGLT2I, DPP4I or GLP1a: A population-based cohort study

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