Major adverse cardiovascular and limb events in patients with diabetes and concomitant peripheral artery disease treated with sodium glucose cotransporter 2 inhibitor versus dipeptidyl peptidase-4 inhibitor

Lee, Hsin-Fu; Chen, Shaowei; Liu, Jia‐Rou; Li, Pei-Ru; Wu, Lung‐Sheng; Chang, Shang‐Hung; Yeh, Yung‐Hsin; Kuo, Chi‐Tai; Chan, Yi‐Hsin; See, Lai‐Chu

doi:10.1186/s12933-020-01118-0

Cited by 21 publications

(19 citation statements)

References 45 publications

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“…Our study indicates that the amplitudes of reductions in body weight and blood pressure are associated with risks of lower limb complications, which calls for an additional attention to the alterations in body weight and blood pressure, two common indicators easy and feasible to monitor during the SGLT2i treatment. In studies in which canagliflozin was not included, SGLT2i were associated with lower risks of chronic heart failure and adverse lower limb events compared with DPP4i among patients with T2D and PAD in real-world practice [ 30 ]. It might be assumed that smooth and steady reductions in body weight and blood pressure, which do not exceed the autoregulation threshold, may not increase but reduce the risk of lower limb complications instead.…”

Section: Discussionmentioning

confidence: 99%

SGLT2 inhibitors and lower limb complications: an updated meta‐analysis

Lin

Zhu

Cai

et al. 2021

Cardiovasc Diabetol

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Background To exam the associations between the use of sodium glucose co-transporter 2 inhibitor (SGLT2i) and the risk of lower limb complications, and to analyze the associated factors. Methods Pubmed, Medline, Embase, the Cochrane Center Register of Controlled Trials for Studies and Clinicaltrial.gov were searched from the inception to November 2020. Randomized controlled trials of SGLT2i conducted in population containing diabetic patients with reports of amputation, peripheral arterial disease (PAD) and diabetic foot (DF) events were included. Random-effect model, fixed-effect model and meta-regression analysis were accordingly used. Result The numbers of SGLT2i users versus non-SGLT2i users in the analyses of amputation, PAD and DF were 40,925/33,414, 36,446/28,685 and 31,907/25,570 respectively. Compared with non-SGLT2i users, the risks of amputation and PAD were slightly increased in patients with canagliflozin treatment (amputation: OR = 1.60, 95% CI 1.04 to 2.46; PAD: OR = 1.53, 95 % CI 1.14 to 2.05). Meta-regression analyses indicated that greater weight reduction in SGLT2i users was significantly associated with the increased risks of amputation (β = − 0.461, 95% CI − 0.726 to − 0.197), PAD (β = − 0.359, 95% CI − 0.545 to − 0.172) and DF (β = − 0.476, 95% CI − 0.836 to − 0.116). Lower baseline diastolic blood pressure (β = − 0.528, 95% CI − 0.852 to − 0.205), more systolic blood pressure reduction (β = − 0.207, 95% CI − 0.390 to − 0.023) and more diastolic blood pressure reduction (β = − 0.312, 95% CI − 0.610 to − 0.015) were significantly associated with the increased risks of amputation, PAD and DF respectively in patients with SGLT2i treatment. Conclusions The risks of amputation and PAD were slightly increased in patients with canagliflozin treatment. Reductions in body weight and blood pressure were associated with lower limb complications in patients with SGLT2i treatment.

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Section: Discussionmentioning

confidence: 99%

SGLT2 inhibitors and lower limb complications: an updated meta‐analysis

Lin

Zhu

Cai

et al. 2021

Cardiovasc Diabetol

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“…Moreover, most previous Asian studies of T2D patients mainly focused on cardiovascular or mortality outcomes associated with the use of SGLT2is without analyzing safety outcomes of treatment (e.g., amputation, hospitalized hypoglycemia) ( 14 – 20 ). Additionally, adjustment for competing risk of death to clinical outcomes of interest (e.g., CVDs) was not considered in previous analyses, leading to biased estimates of relative hazards of study outcomes ( 14 – 17 , 21 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular Benefits With Favorable Renal, Amputation and Hypoglycemic Outcomes of SGLT-2 Inhibitors in Type 2 Diabetes From the Asian Perspective: A Population-Based Cohort Study and Systematic Review

et al. 2022

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ObjectiveWe assessed the effects of sodium glucose cotransporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) in a large real-world Asian cohort with type 2 diabetes (T2D) and performed a systematic review with integrating the present study findings to provide up-to-date evidence from the Asian perspective.MethodsNew users of SGLT2is or DPP4is were identified from the Taiwan’s National Health Insurance Research Database and followed until 2018. Primary outcomes were hospitalization for heart failure (HHF) and three-point major adverse cardiovascular event (3P-MACE; namely, myocardial infarction [MI], stroke, or cardiovascular death). Other outcomes included all-cause death, chronic kidney disease (CKD), amputation, and hospitalized hypoglycemia. Subdistribution hazard models were employed to assess treatment-associated clinical outcomes.ResultsA total of 21,329 SGLT2i and DPP4i propensity-score-matched pairs were analyzed. SGLT2is versus DPP4is showed lower risks of HHF (hazard ratio [95% CI]: 0.52 [0.45–0.59]), 3P-MACE (0.62 [0.55–0.70]), MI (0.63 [0.50–0.79]), stroke (0.60 [0.51–0.70]), all-cause death (0.57 [0.49–0.67]), CKD (0.46 [0.43–0.50]), amputation (0.64 [0.42–0.98]), and hospitalized hypoglycemia (0.54 [0.45–0.64]). Our results were consistent with findings from a systematic review.ConclusionAmong Asian patients with T2D, SGLT2is versus DPP4is showed benefits for several clinical outcomes. More research is warranted to explore the heterogeneous treatment effects of SGLT2is and DPP4is by race/ethnicity.

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“…However, the SGLT2 inhibitor group showed lower risks of congestive heart failure (HR: 0.66; 95% CI 0.49–0.89; p = 0.0062), lower limb ischemia requiring revascularization (HR: 0.73; 95% CI 0.54–0.98; p = 0.0367) or amputation (HR: 0.43; 95% CI 0.30–0.62; p < 0.0001) and cardiovascular death (HR: 0.67; 95% CI 0.49–0.90; p = 0.0089) compared to those in the DPP-4 inhibitor group. [ 119 ].…”

Section: Clinical Evidence Of Sglt2 Inhibitors Against Cvdmentioning

confidence: 99%

Effects of SGLT2 Inhibitors on Atherosclerosis: Lessons from Cardiovascular Clinical Outcomes in Type 2 Diabetic Patients and Basic Researches

Hirai

Koya

et al. 2021

JCM

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Atherosclerosis-caused cardiovascular diseases (CVD) are the leading cause of mortality in type 2 diabetes mellitus (T2DM). Sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective oral drugs for the treatment of T2DM patients. Multiple pre-clinical and clinical studies have indicated that SGLT2 inhibitors not only reduce blood glucose but also confer benefits with regard to body weight, insulin resistance, lipid profiles and blood pressure. Recently, some cardiovascular outcome trials have demonstrated the safety and cardiovascular benefits of SGLT2 inhibitors beyond glycemic control. The SGLT2 inhibitors empagliflozin, canagliflozin, dapagliflozin and ertugliflozin reduce the rates of major adverse cardiovascular events and of hospitalization for heart failure in T2DM patients regardless of CVD. The potential mechanisms of SGLT2 inhibitors on cardioprotection may be involved in improving the function of vascular endothelial cells, suppressing oxidative stress, inhibiting inflammation and regulating autophagy, which further protect from the progression of atherosclerosis. Here, we summarized the pre-clinical and clinical evidence of SGLT2 inhibitors on cardioprotection and discussed the potential molecular mechanisms of SGLT2 inhibitors in preventing the pathogenesis of atherosclerosis and CVD.

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Major adverse cardiovascular and limb events in patients with diabetes and concomitant peripheral artery disease treated with sodium glucose cotransporter 2 inhibitor versus dipeptidyl peptidase-4 inhibitor

Cited by 21 publications

References 45 publications

SGLT2 inhibitors and lower limb complications: an updated meta‐analysis

SGLT2 inhibitors and lower limb complications: an updated meta‐analysis

Cardiovascular Benefits With Favorable Renal, Amputation and Hypoglycemic Outcomes of SGLT-2 Inhibitors in Type 2 Diabetes From the Asian Perspective: A Population-Based Cohort Study and Systematic Review

Effects of SGLT2 Inhibitors on Atherosclerosis: Lessons from Cardiovascular Clinical Outcomes in Type 2 Diabetic Patients and Basic Researches

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