Blood glucose reduction by diabetic drugs with minimal hypoglycaemia risk for cardiovascular outcomes: Evidence from meta‐regression analysis of randomized controlled trials

Huang, Chi‐Jung; Wang, Wei‐Ting; Sung, Shih‐Hsien; Chen, Chen‐Huan; Lip, Gregory Y.H.; Cheng, Hao‐Min; Chiang, Chern‐En

doi:10.1111/dom.13342

Cited by 15 publications

(24 citation statements)

References 47 publications

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“…Hypoglycaemia due to anti‐hyperglycaemic drugs causes significant morbidity and occasional mortality, limiting maintenance of euglycaemia . A meta‐regression analysis suggested that HbA1c reduction was significantly associated with a decreased risk of major cardiovascular events . Furthermore, an anti‐hyperglycaemic drug, which improves cardiovascular outcomes, is considered to be the therapeutic agent of choice .…”

Section: Discussionmentioning

confidence: 99%

“…22 A meta-regression analysis suggested that HbA1c reduction was significantly associated with a decreased risk of major cardiovascular events. 23 Furthermore, an anti-hyperglycaemic drug, which improves cardiovascular outcomes, is considered to be the therapeutic agent of choice. 24,25 Both pioglitazone and SGLT-2 are associated with reduction of major cardiovascular events.…”

Section: Discussionmentioning

confidence: 99%

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Sodium‐glucose cotransporter 2 inhibitor plus pioglitazone vs pioglitazone alone in patients with diabetes mellitus: A systematic review and meta‐analysis of randomized controlled trials

Liao¹,

Sue

et al. 2018

Endocrino Diabet & Metabol

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Summary Aims To evaluate the efficacy and safety of combined therapy with sodium‐glucose cotransporter 2 (SGLT‐2) inhibitors plus pioglitazone versus pioglitazone alone in type 2 diabetic patients. Materials and Methods Systematic literature searches were performed across PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and clinicaltrials.gov from 1966 to September 2018 to identify randomized, controlled trials. Mean difference (MD) or odds ratio (OR) was used to evaluate efficacy and safety end‐points (active group vs control group), wherever appropriate. Heterogeneity was assessed by P value of χ 2 statistics and I 2 . Results Four randomized controlled trials with 1411 diabetic patients were included. Pooling data from included trials showed that HbA1c change was significantly larger in both low‐dose SGLT‐2 inhibitors (MD: −0.59%, 95% CI: −0.77 to −0.41%) and high‐dose SGLT‐2 inhibitors (MD: −0.65%, 95% CI: −0.78 to −0.53%) plus pioglitazone than pioglitazone alone in 24‐26 weeks. Favourable outcomes were also found in fasting blood glucose level reduction and more patients achieving HbA1c <7% in SGLT‐2 inhibitor plus pioglitazone (OR: 3.21, 95% CI: 1.99 to 5.16). Also, SGLT‐2 inhibitor plus pioglitazone vs pioglitazone, reduced weight and blood pressure. The risks of death, heart failure, hypoglycaemia and urinary tract infection were not different between active and control groups although genital tract infection was more frequently seen in SGLT‐2 inhibitor group. Conclusions Compared to pioglitazone alone, SGLT‐2 inhibitor plus pioglitazone improved glycaemic control, reduced body weight and lowered blood pressure, but increased genital tract infection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sodium‐glucose cotransporter 2 inhibitor plus pioglitazone vs pioglitazone alone in patients with diabetes mellitus: A systematic review and meta‐analysis of randomized controlled trials

Liao¹,

Sue

et al. 2018

Endocrino Diabet & Metabol

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“…In the specific case of HbA1c, no systematic reviews of RCTs were identified that allow validating HbA1c as a surrogate in DM studies. Even though two recent systematic reviews evaluated the association between HbA1c reduction and diabetic complications with data from RCTs with antihyperglycemic drugs, these did not adequately report the correlation values ( R -values with their corresponding 95 percent CIs) that allow conclusions to be drawn about the predictive capacity of HbA1c (15;16).…”

Section: Introductionmentioning

confidence: 99%

Glycated hemoglobin as a surrogate for evaluating the effectiveness of drugs in diabetes mellitus trials: a systematic review and trial-level meta-analysis

Rivera

Rodríguez-Zúñiga

Caballero-Alvarado

et al. 2021

Int J Technol Assess Health Care

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Objective The objective of this study was to investigate whether glycated hemoglobin (HbA1c) is a valid surrogate for evaluating the effectiveness of antihyperglycemic drugs in diabetes mellitus (DM) trials. Methods We conducted a systematic review of placebo-controlled randomized clinical trials (RCTs) evaluating the effect of a treatment on HbA1c (mean difference between groups) and clinical outcomes (relative risk of mortality, myocardial infarction, stroke, heart failure, and/or kidney injury) in patients with DM. Then, we investigated the association between treatment effects on HbA1c and clinical outcomes using regression analysis at the trial level. Lastly, we interpreted the correlation coefficients (R) using the cut-off points suggested by the Institute for Quality and Efficiency in Healthcare (IQWiG). HbA1c was considered a valid surrogate if it demonstrated a strong association: lower limit of the 95 percent confidence interval (95 percent CI) of R greater than or equal to .85. Results Nineteen RCTs were identified. All studies included adults with type 2 DM. None of the associations evaluated was strong enough to validate HbA1c as a surrogate for any clinical outcome: mortality (R = .34; 95 percent CI −.14 to .69), myocardial infarction (R = .20; −.30 to .61), heart failure (R = .08; −.40 to .53), kidney injury (R = −.04; −.52 to .47), and stroke (R = .81; .54 to .93). Conclusions The evidence from multiple placebo-controlled RCTs does not support the use of HbA1c as a surrogate to measure the effectiveness of antihyperglycemic drugs in DM studies.

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“…The risk increases with each risk factor above target . A meta‐analysis of randomized controlled trials (RCTs) has shown a linear relationship between the reduction in HbA 1c and major cardiovascular events . Another meta‐analysis of RCTs, showed that reaching blood pressure targets was associated with decreased risk of diabetes‐related mortality .…”

Section: Introductionmentioning

confidence: 99%

Variation in the achievement of HbA_1c, blood pressure and LDL cholesterol targets in type 2 diabetes in general practice and characteristics associated with risk factor control

et al. 2019

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To identify population, general practitioner, and practice characteristics associated with the achievement of HbA 1c , blood pressure and LDL cholesterol targets, and to describe variation in the achievement of risk factor control. Methods We conducted a cross-sectional survey of 9342 people with type 2 diabetes, 281 general practitioners and 77 general practices in Norway. Missing values (7.4%) were imputed using multiple imputation by chained equations. We used three-level logistic regression with the achievement of HbA 1c , blood pressure and LDL cholesterol targets as dependent variables, and factors related to population, general practitioners, and practices as independent variables. Results Treatment targets were achieved for HbA 1c in 64%, blood pressure in 50%, and LDL cholesterol in 52% of people with type 2 diabetes, and 17% met all three targets. There was substantial heterogeneity in target achievement among general practitioners and among practices; the estimated proportion of a GPs diabetes population at target was 55-73% (10-90 percentiles) for HbA 1c , 36-63% for blood pressure, and 47-57% for LDL cholesterol targets. The models explained 11%, 5% and 14%, respectively, of the total variation in the achievement of HbA 1c , blood pressure and LDL cholesterol targets. Use among general practitioners of a structured diabetes form was associated with 23% higher odds of achieving the HbA 1c target (odds ratio 1.23, 95% confidence interval (CI) 1.02-1.47) and 17% higher odds of achieving the LDL cholesterol target (odds ratio 1.17, 95% CI 1.01-1.35). Conclusions Clinical diabetes management is difficult, and few people meet all three risk factor control targets. The proportion of people reaching target varied among general practitioners and practices. Several population, general practitioner and practice characteristics only explained a small part of the total variation. The use of a structured diabetes form is recommended.

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Blood glucose reduction by diabetic drugs with minimal hypoglycaemia risk for cardiovascular outcomes: Evidence from meta‐regression analysis of randomized controlled trials

Abstract: Compared with placebo, newer T2D agents with less hypoglycaemic hazard significantly reduced the risk of MACE. The MACE reduction appears to be associated with HbA1c reduction in a linear relationship.

Cited by 15 publications

References 47 publications

Sodium‐glucose cotransporter 2 inhibitor plus pioglitazone vs pioglitazone alone in patients with diabetes mellitus: A systematic review and meta‐analysis of randomized controlled trials

Sodium‐glucose cotransporter 2 inhibitor plus pioglitazone vs pioglitazone alone in patients with diabetes mellitus: A systematic review and meta‐analysis of randomized controlled trials

Glycated hemoglobin as a surrogate for evaluating the effectiveness of drugs in diabetes mellitus trials: a systematic review and trial-level meta-analysis

Variation in the achievement of HbA_1c, blood pressure and LDL cholesterol targets in type 2 diabetes in general practice and characteristics associated with risk factor control

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Blood glucose reduction by diabetic drugs with minimal hypoglycaemia risk for cardiovascular outcomes: Evidence from meta‐regression analysis of randomized controlled trials

Abstract: Compared with placebo, newer T2D agents with less hypoglycaemic hazard significantly reduced the risk of MACE. The MACE reduction appears to be associated with HbA1c reduction in a linear relationship.

Cited by 15 publications

References 47 publications

Sodium‐glucose cotransporter 2 inhibitor plus pioglitazone vs pioglitazone alone in patients with diabetes mellitus: A systematic review and meta‐analysis of randomized controlled trials

Sodium‐glucose cotransporter 2 inhibitor plus pioglitazone vs pioglitazone alone in patients with diabetes mellitus: A systematic review and meta‐analysis of randomized controlled trials

Glycated hemoglobin as a surrogate for evaluating the effectiveness of drugs in diabetes mellitus trials: a systematic review and trial-level meta-analysis

Variation in the achievement of HbA1c, blood pressure and LDL cholesterol targets in type 2 diabetes in general practice and characteristics associated with risk factor control

Contact Info

Product

Resources

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Variation in the achievement of HbA_1c, blood pressure and LDL cholesterol targets in type 2 diabetes in general practice and characteristics associated with risk factor control