Dataset Information

Comparative effects of sulphonylureas, dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors added to metformin monotherapy: a propensity-score matched cohort study in UK primary care.

ABSTRACT:

Aim

To assess the comparative effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors, sulphonylureas (SUs) and dipeptidyl peptidase-4 (DPP-4) inhibitors on cardiometabolic risk factors in routine care.

Materials and methods

Using primary care data on 10?631 new users of SUs, SGLT2 inhibitors or DPP-4 inhibitors added to metformin, obtained from the UK Clinical Practice Research Datalink, we created propensity-score matched cohorts and used linear mixed models to describe changes in glycated haemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), systolic blood pressure (BP) and body mass index (BMI) over 96?weeks.

Results

HbA1c levels fell substantially after treatment intensification for all drugs: mean change at week 12: SGLT2 inhibitors: -15.2?mmol/mol (95% confidence interval [CI] -16.9, -13.5); SUs: -14.3?mmol/mol (95% CI -15.5, -13.2); and DPP-4 inhibitors: -11.9?mmol/mol (95% CI -13.1, -10.6). Systolic BP fell for SGLT2 inhibitor users throughout follow-up, but not for DPP-4 inhibitor or SU users: mean change at week 12: SGLT2 inhibitors: -2.3?mmHg (95% CI -3.8, -0.8); SUs: -0.8?mmHg (95% CI -1.9, +0.4); and DPP-4 inhibitors: -0.9?mmHg (95% CI -2.1,+0.2). BMI decreased for SGLT2 inhibitor and DPP-4 inhibitor users, but not SU users: mean change at week 12: SGLT2 inhibitors: -0.7?kg/m² (95% CI -0.9, -0.5); SUs: 0.0?kg/m² (95% CI -0.3, +0.2); and DPP-4 inhibitors: -0.3?kg/m² (95% CI -0.5, -0.1). eGFR fell at 12?weeks for SGLT2 inhibitor and DPP-4 inhibitor users. At 60?weeks, the fall in eGFR from baseline was similar for each drug class.

Conclusions

In routine care, SGLT2 inhibitors had greater effects on cardiometabolic risk factors than SUs. Routine care data closely replicated the effects of diabetes drugs on physiological variables measured in clinical trials.

SUBMITTER: Wilkinson S

PROVIDER: S-EPMC7187358 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Comparative effects of sulphonylureas, dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors added to metformin monotherapy: a propensity-score matched cohort study in UK primary care.

Wilkinson Samantha S Williamson Elizabeth E Pokrajac Ana A Fogarty Damian D Stirnadel-Farrant Heide H Smeeth Liam L Douglas Ian J IJ Tomlinson Laurie A LA

Diabetes, obesity & metabolism 20200213 5

<h4>Aim</h4>To assess the comparative effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors, sulphonylureas (SUs) and dipeptidyl peptidase-4 (DPP-4) inhibitors on cardiometabolic risk factors in routine care.<h4>Materials and methods</h4>Using primary care data on 10 631 new users of SUs, SGLT2 inhibitors or DPP-4 inhibitors added to metformin, obtained from the UK Clinical Practice Research Datalink, we created propensity-score matched cohorts and used linear mixed models to describe ch ...[more]

PMID: 31957254

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Project description:ObjectiveTo quantify the risk of hypoglycaemia associated with the concomitant use of dipeptidyl peptidase-4 (DPP-4) inhibitors and sulphonylureas compared with placebo and sulphonylureas.DesignSystematic review and meta-analysis.Data sourcesMedline, ISI Web of Science, SCOPUS, Cochrane Central Register of Controlled Trials, and clinicaltrial.gov were searched without any language restriction.Study selectionPlacebo controlled randomised trials comprising at least 50 participants with type 2 diabetes treated with DPP-4 inhibitors and sulphonylureas.Review methodsRisk of bias in each trial was assessed using the Cochrane Collaboration tool. The risk ratio of hypoglycaemia with 95% confidence intervals was computed for each study and then pooled using fixed effect models (Mantel Haenszel method) or random effect models, when appropriate. Subgroup analyses were also performed (eg, dose of DPP-4 inhibitors). The number needed to harm (NNH) was estimated according to treatment duration.Results10 studies were included, representing a total of 6546 participants (4020 received DPP-4 inhibitors plus sulphonylureas, 2526 placebo plus sulphonylureas). The risk ratio of hypoglycaemia was 1.52 (95% confidence interval 1.29 to 1.80). The NNH was 17 (95% confidence interval 11 to 30) for a treatment duration of six months or less, 15 (9 to 26) for 6.1 to 12 months, and 8 (5 to 15) for more than one year. In subgroup analysis, no difference was found between full and low doses of DPP-4 inhibitors: the risk ratio related to full dose DPP-4 inhibitors was 1.66 (1.34 to 2.06), whereas the increased risk ratio related to low dose DPP-4 inhibitors did not reach statistical significance (1.33, 0.92 to 1.94).ConclusionsAddition of DPP-4 inhibitors to sulphonylurea to treat people with type 2 diabetes is associated with a 50% increased risk of hypoglycaemia and to one excess case of hypoglycaemia for every 17 patients in the first six months of treatment. This highlights the need to respect recommendations for a decrease in sulphonylureas dose when initiating DPP-4 inhibitors and to assess the effectiveness of this risk minimisation strategy.

Project description:Introduction: The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I) and dipeptidyl peptidase-4 inhibitors (DPP4I) on new-onset cognitive dysfunction in type 2 diabetes mellitus remain unknown. This study aimed to evaluate the effects of the two novel antidiabetic agents on cognitive dysfunction by comparing the rates of dementia between SGLT2I and DPP4I users. Methods: This was a population-based cohort study of type 2 diabetes mellitus patients treated with SGLT2I and DPP4I between January 1, 2015 and December 31, 2019 in Hong Kong. Exclusion criteria were <1-month exposure or exposure to both medication classes, or prior diagnosis of dementia or major neurological/psychiatric diseases. Primary outcomes were new-onset dementia, Alzheimer's, and Parkinson's. Secondary outcomes were all-cause, cardiovascular, and cerebrovascular mortality. Results: A total of 13,276 SGLT2I and 36,544 DPP4I users (total n = 51,460; median age: 66.3 years old [interquartile range (IQR): 58-76], 55.65% men) were studied (follow-up: 472 [120-792] days). After 1:2 matching (SGLT2I: n = 13,283; DPP4I: n = 26,545), SGLT2I users had lower incidences of dementia (0.19 vs. 0.78%, p < 0.0001), Alzheimer's (0.01 vs. 0.1%, p = 0.0047), Parkinson's disease (0.02 vs. 0.14%, p = 0.0006), all-cause (5.48 vs. 12.69%, p < 0.0001), cerebrovascular (0.88 vs. 3.88%, p < 0.0001), and cardiovascular mortality (0.49 vs. 3.75%, p < 0.0001). Cox regression showed that SGLT2I use was associated with lower risks of dementia (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: [0.27-0.61], P < 0.0001), Parkinson's (HR:0.28, 95% CI: [0.09-0.91], P = 0.0349), all-cause (HR:0.84, 95% CI: [0.77-0.91], P < 0.0001), cardiovascular (HR:0.64, 95% CI: [0.49-0.85], P = 0.0017), and cerebrovascular (HR:0.36, 95% CI: [0.3-0.43], P < 0.0001) mortality. Conclusions: The use of SGLT2I is associated with lower risks of dementia, Parkinson's disease, and cerebrovascular mortality compared with DPP4I use after 1:2 ratio propensity score matching.

Dataset Information

Comparative effects of sulphonylureas, dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors added to metformin monotherapy: a propensity-score matched cohort study in UK primary care.

Aim

Materials and methods

Results

Conclusions

Publications

Comparative effects of sulphonylureas, dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors added to metformin monotherapy: a propensity-score matched cohort study in UK primary care.

Similar Datasets

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