Cardiovascular events associated with second‐line anti‐diabetes treatments: analysis of real‐world Korean data

Ha, Kyoung Hwa; Kim, B.; Choi, Heekyoung; Kim, D. J.; Kim, H. C.

doi:10.1111/dme.13384

Cited by 12 publications

(16 citation statements)

References 31 publications

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“…Also, they report an elevated risk for add‐on sulfonylureas compared with add‐on thiazolidinediones (specifically pioglitazone). Similar findings have been found from data from other healthcare systems, such as the Taiwan National Health Insurance Database , the Swedish National Diabetes Registry and the Korean National Health Insurance Database .…”

Section: Discussionsupporting

confidence: 87%

Long‐term comparative safety analysis of the risks associated with adding or switching to a sulfonylurea as second‐line Type 2 diabetes mellitus treatment in a US veteran population

2018

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Aim To examine the risks of all‐cause mortality and cardiovascular events associated with adding vs switching to second‐line therapies in a comparative safety study of people with Type 2 diabetes mellitus. Methods We conducted a retrospective cohort study using an as‐treated analysis of people served by the Veterans Health Administration who were on metformin and subsequently augmented this treatment or switched to other oral glucose‐lowering treatments between 1998 and 2012. This study included 145 250 people with long follow‐up. Confounding was addressed through several strategies, involving weighted propensity score models with rich confounder adjustment and strict inclusion criteria, coupled with an incident‐user design. Results Second‐line use of sulfonylureas was related to higher mortality (hazard ratio 1.39, 95% CI 1.14, 1.70) and cardiovascular risks (hazard ratio 1.19, 95% CI 1.09, 1.30) compared with thiazolidinedione therapy. Differential hazards were associated with discontinuing or not discontinuing metformin; switching to sulfonylurea therapy was associated with a higher risk of all‐cause mortality and cardiovascular events compared with all other therapies. Furthermore, add‐on sulfonylurea therapy was associated with an elevated risk for both outcomes when compared with thiazolidinedione add‐on therapy. Conclusions The results of the present study may inform decisions on whether to augment or discontinue metformin; when considering the long‐term risks, switching to a sulfonylurea appears unfavourable compared with other therapies. Instead, adding a thiazolidinedione to existing metformin therapy appears to be superior to adding or switching to a sulfonylurea.

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Section: Discussionsupporting

confidence: 87%

Long‐term comparative safety analysis of the risks associated with adding or switching to a sulfonylurea as second‐line Type 2 diabetes mellitus treatment in a US veteran population

2018

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“…Zghebi et al found that TZD as an add-on medication to metformin was associated with lower risk of major cardiovascular disease or death, when compared with a SU add-on treatment to metformin in an UK Clinical Practice Research Datalink [ 26 ]. Recently, a Korean Health Insurance Service Study showed that TZD as a second-line drug to metformin had relatively lower risk of CVD compared to SU, although these findings did not reach statistical significance [ 20 ]. Similar to these previous studies, we observed that both TZD and AGI as the second-line ADAs added to metformin were associated with decreased cardiovascular risk including death, stroke and ACS, although the comparators were different [ 18 , 19 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…In a Korean Health Insurance Review and Assessment Database Study, TZD (pioglitazone) added to metformin was associated with a decreased total CVD risk in patients with T2DM [ 19 ]. Another Korean Health Insurance Database Study showed that DPP-4I added to metformin had a lower CVD risk than SU added to metformin in T2DM patients [ 20 ]. However, Chang et al using a Taiwan Diabetic Database, found that there were no differences in cardiovascular risk among several different add-on second-line oral ADAs, in a newly diagnosed diabetic population [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Glitazones and alpha-glucosidase inhibitors as the second-line oral anti-diabetic agents added to metformin reduce cardiovascular risk in Type 2 diabetes patients: a nationwide cohort observational study

Chan

Lin

et al. 2018

Cardiovasc Diabetol

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ObjectiveMetformin is the standard first-line drug for patients with Type 2 diabetes (T2DM). However, the optimal second-line oral anti-diabetic agent (ADA) remains unclear. We investigated the cardiovascular risk of various ADAs used as add-on medication to metformin in T2DM patients from a nationwide cohort.MethodsT2DM patients using different add-on oral ADAs after an initial metformin therapy of > 90 days were identified from the Taiwan National Health Insurance Database. Five classes of ADAs, including sulphonylureas (SU), glinides, thiazolidinediones (TZD), alpha-glucosidase inhibitors (AGI), and dipeptidyl peptidase-4 inhibitors (DPP-4I) were selected for analysis. The reference group was the SU added to metformin. Patients were excluded if aged < 20 years, had a history of stroke or acute coronary syndrome (ACS), or were receiving insulin treatment. The primary outcomes included any major adverse cardiovascular event (MACE) including ACS, ischemic/hemorrhagic stroke, and death. A Cox regression model was used to estimate the hazard ratio (HR) for MACE.ResultsA total of 26,742 patients receiving their add-on drug to metformin of either SU (n = 24,277), glinides (n = 962), TZD (n = 581), AGI (n = 808), or DPP-4I (n = 114) were analyzed. After a mean follow-up duration of 6.6 ± 3.4 years, a total of 4775 MACEs occurred. Compared with the SU+metformin group (reference), the TZD+metformin (adjusted HR: 0.66; 95% CI 0.50–0.88, p = 0.004) and AGI+metformin (adjusted HR: 0.74; 95% CI 0.59–0.94, p = 0.01) groups showed a significantly lower risk of MACE.ConclusionBoth TZD and AGI, when used as an add-on drug to metformin were associated with lower MACE risk when compared with SU added to metformin in this retrospective cohort study.Trial registration CE13152B-3. Registered 7 Mar, 2013, retrospectively registeredElectronic supplementary materialThe online version of this article (10.1186/s12933-018-0663-6) contains supplementary material, which is available to authorized users.

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“…Previous studies have suggested that DPP-4i as a monotherapy or in combination with other oral hypoglycemic agents has potentially beneficial effects on cardiovascular outcomes. 3) 4) 5) 6) A recent study by Ha et al, 6) based on the 2011–2015 Korean National Health Insurance Service (NHIS) database, reported that people with type 2 diabetes who added a DPP-4i as a second-line drug to metformin had lower risks of cardiovascular disease (CVD) and all-cause mortality, compared to those who added sulfonylurea. However, there are some practical differences between the DPP-4is such as duration of action, metabolism, elimination, and isolated compound-specific characteristics.…”

Section: Introductionmentioning

confidence: 99%

Comparative Cardiovascular Risks of Dipeptidyl Peptidase-4 Inhibitors: Analyses of Real-world Data in Korea

Kim

Shin

et al. 2018

Korean Circ J

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Background and ObjectivesTo compare cardiovascular disease (CVD) risk associated with 5 different dipeptidyl peptidase-4 inhibitors (DPP-4is) in people with type 2 diabetes.MethodsWe identified 534,327 people who were newly prescribed sitagliptin (n=167,157), vildagliptin (n=67,412), saxagliptin (n=29,479), linagliptin (n=220,672), or gemigliptin (n=49,607) between January 2013 and June 2015 using the claims database of the Korean National Health Insurance System. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for major CVD events (myocardial infarction, stroke, or death) among users of different DPP-4is. The model was adjusted for sex, age, duration of DPP-4i use, use of other glucose-lowering drugs, use of antiplatelet agents, hypertension, dyslipidemia, atrial fibrillation, chronic kidney disease, microvascular complications of diabetes, Charlson comorbidity index, and the calendar index year as potential confounders.ResultsCompared to sitagliptin users, the fully adjusted HRs for CVD events were 0.97 (95% confidence interval [CI], 0.94–1.01; p=0.163) for vildagliptin, 0.76 (95% CI, 0.71–0.81; p<0.001) for saxagliptin, 0.95 (95% CI, 0.92–0.98; p<0.001) for linagliptin, and 0.84 (95% CI, 0.80–0.88; p<0.001) for gemigliptin.ConclusionsCompared to sitagliptin therapy, saxagliptin, linagliptin, and gemigliptin therapies were all associated with a lower risk of cardiovascular events.

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Cardiovascular events associated with second‐line anti‐diabetes treatments: analysis of real‐world Korean data

Abstract: Analysis of Korea National Health Insurance database showed that MET + DPP4i treatment for diabetes had a lower CVD risk than MET + SU treatment.

Cited by 12 publications

References 31 publications

Long‐term comparative safety analysis of the risks associated with adding or switching to a sulfonylurea as second‐line Type 2 diabetes mellitus treatment in a US veteran population

Long‐term comparative safety analysis of the risks associated with adding or switching to a sulfonylurea as second‐line Type 2 diabetes mellitus treatment in a US veteran population

Glitazones and alpha-glucosidase inhibitors as the second-line oral anti-diabetic agents added to metformin reduce cardiovascular risk in Type 2 diabetes patients: a nationwide cohort observational study

Comparative Cardiovascular Risks of Dipeptidyl Peptidase-4 Inhibitors: Analyses of Real-world Data in Korea

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