Metformin combined with dipeptidyl peptidase-4 inhibitors or metformin combined with sulfonylureas in patients with type 2 diabetes: A real world analysis of the South Korean national cohort

Cho, Yeon Young; Cho, Sung-Il

doi:10.1016/j.metabol.2018.03.009

Cited by 5 publications

(4 citation statements)

References 53 publications

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“…Our study findings are consistent with recent retrospective studies from the UK, Sweden, Taiwan, and Korea that evaluated the safety of sulfonylureas compared with DPP4 inhibitors when added on to metformin. [15][16][17][18][19] In two cohort studies using the UK Clinical Practice Research Datalink, investigators noted an increased risk of cardiovascular-related and all-cause mortality in patients prescribed sulfonylureas. Similarly, in three independent analyses from Sweden, Taiwan, and Korea, an increased risk of mortality, cardiovascular events, and hypoglycemia was noted in patients prescribed sulfonylureas.…”

Section: Discussionmentioning

confidence: 99%

“…Many observational studies have compared DPP4 inhibitors with sulfonylureas when in combination with metformin and most have found lower risks of mortality and cardiovascular disease. [15][16][17][18][19] However, comparisons between sulfonylureas and other OHAs in this setting are much less common. In this observational, populationwide study, we set out to compare all-cause mortality, cardiovascular events, and major hypoglycemic episodes in patients using metformin who were newly prescribed sulfonylureas compared with other OHAs (older and newer agents) in a real-world setting.…”

mentioning

confidence: 99%

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Safety of add-on sulfonylurea therapy in patients with type 2 diabetes using metformin: a population-based real-world study

Hougen

Whitlock

Komenda

et al. 2021

BMJ Open Diab Res Care

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IntroductionMetformin is the initial oral antihyperglycemic agent (OHA) of choice for most patients with type 2 diabetes (T2D). However, more than one agent is often required for optimal glucose control. As the choice of preferred second OHAs is less well defined, we sought to compare the real-world safety of sulfonylureas to other OHAs as add-on therapy to metformin in patients with T2D.Research design and methodsThis retrospective cohort study included adults in Manitoba, Canada with T2D from 2006 to 2017. Using a new-user design, we divided patients who started on metformin into two groups: add-on therapy with a sulfonylurea and add-on therapy with a different OHA. Outcomes included all-cause mortality, cardiovascular events, and major hypoglycemic episodes. We calculated propensity scores and applied inverse probability of treatment weights to each individual. We compared groups using Cox proportional hazards regression and explored differences in HRs between pre-2008 (acarbose, meglitinides, and thiazolidinediones) and post-2008 (dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose linked transporter-2 inhibitors) OHAs.ResultsOur cohort included 32 576 individuals (28 077 metformin plus sulfonylurea and 4499 metformin plus ‘other’). Patients newly prescribed a sulfonylurea in the setting of metformin had a higher risk of all-cause mortality (HR 1.44, 95% CI 1.12 to 1.84, p=0.005) and major hypoglycemic episodes (HR 2.78, 95% CI 1.66 to 4.66, p<0.001) than those prescribed an ‘other’ OHA. No differences in cardiovascular events were observed (HR 0.99, 95% CI 0.81 to 1.22, p=0.92). In subgroup analyses, mortality and cardiovascular event risk was higher in patients prescribed sulfonylureas versus post-2008 OHAs.ConclusionsSulfonylureas as add-on therapy to metformin are associated with increased risk of all-cause mortality and major hypoglycemic episodes compared with ‘other’ OHAs. Post hoc analysis suggests newer OHAs may be preferred to sulfonylureas as second-line therapy for glycemic control.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Safety of add-on sulfonylurea therapy in patients with type 2 diabetes using metformin: a population-based real-world study

Hougen

Whitlock

Komenda

et al. 2021

BMJ Open Diab Res Care

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“…In terms of blood glucose control, the combination therapy of sulfonylureas with metformin has shown a similar efficacy of glucose-lowering as other dual combinations, and there was no significant difference in the change of HbA1 among different combinations before and after the treatment (98). However, in other real-world analyses based on different populations, the combination of sulfonylureas with metformin have a higher risk of hypoglycemia events, cardiovascular events, and all-cause mortality compared with other oral anti-diabetic agent added to metformin (99)(100)(101). It suggested that with comparable glycemic effects, other oral anti-hyperglycemic agents may be a preferable option as adjunctive to metformin than sulfonylureas.…”

Section: Biguanides + Sulphonylureasmentioning

confidence: 96%

Benefits and risks of drug combination therapy for diabetes mellitus and its complications: a comprehensive review

Xie,

Wu,

Hao

et al. 2023

Front. Endocrinol.

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Diabetes is a chronic metabolic disease, and its therapeutic goals focus on the effective management of blood glucose and various complications. Drug combination therapy has emerged as a comprehensive treatment approach for diabetes. An increasing number of studies have shown that, compared with monotherapy, combination therapy can bring significant clinical benefits while controlling blood glucose, weight, and blood pressure, as well as mitigating damage from certain complications and delaying their progression in diabetes, including both type 1 diabetes (T1D), type 2 diabetes (T2D) and related complications. This evidence provides strong support for the recommendation of combination therapy for diabetes and highlights the importance of combined treatment. In this review, we first provided a brief overview of the phenotype and pathogenesis of diabetes and discussed several conventional anti-diabetic medications currently used for the treatment of diabetes. We then reviewed several clinical trials and pre-clinical animal experiments on T1D, T2D, and their common complications to evaluate the efficacy and safety of different classes of drug combinations. In general, combination therapy plays a pivotal role in the management of diabetes. Integrating the effectiveness of multiple drugs enables more comprehensive and effective control of blood glucose without increasing the risk of hypoglycemia or other serious adverse events. However, specific treatment regimens should be tailored to individual patients and implemented under the guidance of healthcare professionals.

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“…[3][4][5][6] The CAROLINA 7 was the only large, randomized, active comparator trial of DPP-4i (linagliptin) vs. sulfonylureas (SU; glimepiride), another commonly used GLA, and it revealed that the use of DPP-4i relative to SU did not yield beneficial cardiovascular effects either. Nevertheless, our literature review ( Table S1) has found that numerous cohort studies [8][9][10][11][12][13][14][15][16][17] for assessing long-term comparative risks of cardiovascular diseases (CVDs) associated with the real-world use of DPP-4i vs. SU showed the significantly reduced risks of CVDs from DPP-4i vs. SU.…”

mentioning

confidence: 99%

Heterogeneous Treatment Effects on Cardiovascular Diseases With Dipeptidyl Peptidase‐4 Inhibitors Versus Sulfonylureas in Type 2 Diabetes Patients

Chen

Lin

et al. 2020

Clin Pharma and Therapeutics

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This study explored heterogeneous treatment effects (HTEs) of the real‐world use of dipeptidyl peptidase‐4 inhibitors (DPP‐4is) vs. sulfonylureas (SUs) on cardiovascular diseases (CVDs) and mortality in patients with type 2 diabetes. Utilizing Taiwan’s National Health Insurance Research Database, 19,853 propensity score‐matched pairs of DPP‐4i and SU stable users were identified. Classification and regression tree analyses and Cox models were applied to explore HTEs, according to various patient characteristics, on the composite CVDs, three‐point major adverse cardiovascular event (MACE), and all‐cause mortality. The absolute risk difference (ARD), hazard ratio (HR), and 95% confidence interval (CI) were estimated for comparing treatment effects. CVD history, ischemic stroke, or transient ischemic attack (IS/TIA) history, and age at treatment initiation were significant treatment effect modifiers. Patients with prior IS/TIA but without any other prior CVDs benefited most in reduced risks of composite CVDs from using DPP‐4i vs. SU (ARD −4.31%, 95% CI −7.48% to −1.14%, HR 0.81, 95% CI 0.69 ~ 0.95), followed by those without prior IS/TIA and CVDs and initiated with DPP‐4i at age < 69.3 years (ARD −0.90%, 95% CI −1.47% to −0.32%, HR 0.86, 95% CI 0.77 ~ 0.97). Patients with prior IS/TIA benefited most in reduced risks of three‐point MACE from using DPP‐4i vs. SU (ARD −4.22%, 95% CV −6.66% to −1.78%, HR 0.80, 95% CI 0.69 ~ 0.93), followed by those without prior IS/TIA and initiated with DPP‐4i at age < 69.3 years (ARD −0.68%, 95% CI −1.08% to −0.29%, HR 0.81, 95% CI 0.70 ~ 0.93). Consideration of CVD and IS/TIA histories and age could facilitate individualized diabetes management of using DPP‐4i vs. SU. Future studies are warranted given the hypothesis‐generating nature in this exploratory research.

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Metformin combined with dipeptidyl peptidase-4 inhibitors or metformin combined with sulfonylureas in patients with type 2 diabetes: A real world analysis of the South Korean national cohort

Cited by 5 publications

References 53 publications

Safety of add-on sulfonylurea therapy in patients with type 2 diabetes using metformin: a population-based real-world study

Safety of add-on sulfonylurea therapy in patients with type 2 diabetes using metformin: a population-based real-world study

Benefits and risks of drug combination therapy for diabetes mellitus and its complications: a comprehensive review

Heterogeneous Treatment Effects on Cardiovascular Diseases With Dipeptidyl Peptidase‐4 Inhibitors Versus Sulfonylureas in Type 2 Diabetes Patients

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