Duration of Diabetes and Cardiorenal Efficacy of Liraglutide and Semaglutide: A Post Hoc Analysis of the Leader and Sustain-6 Clinical Trials

Verma, Subodh; Bain, Stephen C.; Honoré, Julie Broe; Fries, Tea Monk; Nauck, Michael A.; Pratley, Richard E.; Rasmussen, Søren; Zinman, Bernard; Buse, John B.

doi:10.1016/s0735-1097(19)32310-1

Cited by 3 publications

(4 citation statements)

References 11 publications

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“…Within the context of selection of the right drug for the right patient, a sub‐analysis of the DECLARE trial has shown that dapagliflozin can significantly reduce the risk of MACE by 16% in patients with a history of prior MI, but not in patients with established CVD without prior MI; furthermore, dapagliflozin may prevent and reduce the progression of DKD in T2D patients with preserved renal function, adding evidence that treatment with SGLT‐2i could be useful for early prevention of DKD as well as late . Finally, both liraglutide and semaglutide exhibited consistent benefits concerning cardiorenal endpoints, irrespective of the duration of diabetes . Although many of these findings should be considered hypothesis‐generating, nonetheless, they give some indication for prescribing the right anti‐hyperglycaemic drug to patients who are likely to derive the greatest benefit and least likely to experience serious harm.…”

Section: Selecting the Right Drug For The Right Patientmentioning

confidence: 99%

“…30 Finally, both liraglutide and semaglutide exhibited consistent benefits concerning cardiorenal endpoints, irrespective of the duration of diabetes. 42 Although many of these findings should be considered hypothesisgenerating, nonetheless, they give some indication for prescribing the right anti-hyperglycaemic drug to patients who are likely to derive the greatest benefit and least likely to experience serious harm.…”

Section: Selecting the Right Drug For The Right Patientmentioning

confidence: 99%

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Primary versus secondary cardiorenal prevention in type 2 diabetes: Which newer anti‐hyperglycaemic drug matters?

Giugliano

Ceriello

Nicola

et al. 2019

Diabetes Obesity Metabolism

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We are observing a resurgence of major diabetic vascular complications after a period of dramatic decrease during the period 1990 to 2010. The classical division of cardiovascular prevention into primary (with an event) and secondary (without an event) is largely used to describe cardiovascular risk in type 2 diabetes (T2D); however, there is evidence that the cardiovascular risk in diabetes may range from highest in patients who experienced a previous cardiovascular event to mild in patients with the main risk factors at target. Herein, we present details of the 14 cardiovascular outcome trials (CVOTs) published to date, including the total population investigated, and their separation into primary (T2D + multiple risk factors) and secondary prevention (T2D + established cardiovascular disease [CVD]) populations as detailed within the trials. We also summarize evidence for the effects of dipeptidyl peptidase‐4 inhibitors (DPP‐4i), glucagon‐like peptide‐1 receptor agonists (GLP1‐RA) and sodium glucose co‐transporter‐2 inhibitors (SGLT‐2i) versus placebo on the risk of major cardiovascular events (MACE), heart failure (HF) and diabetic kidney disease (DKD). In primary prevention, SGLT‐2i reduce both the risk of hospitalization for HF and progression of DKD; in secondary prevention, SGLT‐2i are effective on the three endpoints, DPP‐4i are neutral, while GLP1‐RA show mixed results.

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Section: Selecting the Right Drug For The Right Patientmentioning

confidence: 99%

Section: Selecting the Right Drug For The Right Patientmentioning

confidence: 99%

Primary versus secondary cardiorenal prevention in type 2 diabetes: Which newer anti‐hyperglycaemic drug matters?

Giugliano

Ceriello

Nicola

et al. 2019

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

show abstract

“…A post-hoc analysis of the SUSTAIN-6 trial [43] showed that semaglutide reduces the risk of MACE in all the subgroups analyzed, which included grouping by age, gender, and CV risk. The duration of diabetes at baseline, however, seems to affect the outcomes, as demonstrated Melo et al Diabetol Metab Syndr (2021) 13:81 by a post-hoc analysis of the SUSTAIN-6 and LEADER trials [44]. A recent meta-analysis of all the discussed GLP-1 RA CVOTs found no significant heterogeneity across subgroups, which included primary versus secondary prevention, HbAc1 levels, length of follow-up, daily versus weekly administration, homology of the drug to human GLP-1, BMI, age, or baseline eGFR [45].…”

Section: Summary and Discussion Of The Glp-1 Ra Cvots Resultsmentioning

confidence: 98%

Heterogeneity amongst GLP-1 RA cardiovascular outcome trials results: can definition of established cardiovascular disease be the missing link?

Melo

Gavina

Silva-Nunes

et al. 2021

Diabetol Metab Syndr

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Atherosclerotic cardiovascular diseases are the leading cause of adverse outcomes in patients with type 2 diabetes, and all new anti-diabetic agents are mandated to undergo cardiovascular outcome trials (CVOTs). Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are incretin mimetics that reduce blood glucose levels with a low associated risk of hypoglycaemia. CVOTs with different GLP-1 RAs yielded different results in terms of major cardiovascular composite outcome (MACE), with some trials showing superiority in the treatment arm, whereas other simply displayed non-inferiority. More importantly, the significance of each component of MACE varied between drugs. This begs the question of whether these differences are due to dissimilarities between drugs or other factors, namely trial design, are at the root of these differences. We analyse the trial designs for all CVOTs with GLP-1 RAs and highlight important differences between them, namely in terms of definition of established cardiovascular disease, and discuss how these differences might explain the disparate results of the trials and preclude direct comparisons between them. We conclude that a fair comparison between GLP-1 RA CVOTs would involve post-hoc analysis re-grouping the patients into different cardiovascular risk categories based upon their baseline clinical parameters, in order to even out the criteria used to classify patients.

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“…As one of the most essential public health problems worldwide, diabetes mellitus has attracted increasing attention due to the dramatic increase in its incidence and prevalence in recent decades (Gregg et al, 2018; Verma et al, 2019). Epidemiological surveys have shown that more than 440 million individuals have diabetes globally, and the overall prevalence in Chinese adults is approximately 10.9%, with type 2 diabetes being the major type (Wang et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Development and validation of an ultrasensitive LC–MS/MS method for the quantification of cetagliptin in human plasma and its application in a microdose clinical trial

Bai

Lu²,

Cheng

et al. 2020

Biomedical Chromatography

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This study established and validated an LC–MS/MS method for the ultrasensitive determination of cetagliptin in human plasma. Sample pretreatment was achieved by liquid–liquid extraction with ethyl acetate, and chromatographic separation was performed on an XB‐C18 analytical column (50 × 2.1 mm, 5 μm) with gradient elution (0.1% formic acid in acetonitrile and 0.1% formic acid) at a flow rate of 1.0 mL/min. For mass spectrometric detection, multiple reaction monitoring was used, and the ion transitions monitored were m/z 421.2–86.0 for cetagliptin and m/z 424.2–88.0 for cetagliptin‐d3. Method validation was performed according to the U.S. Food and Drug Administration Bioanalytical Method Validation Guidance, for which the calibration curve was linear in the range of 50.0–2000 pg/mL. All of the other results, such as selectivity, lower limit of quantitation, precision, accuracy, matrix effect, recovery, and stability, met the acceptance criteria. The validated method was successfully applied in a microdose clinical trial to systematically investigate the pharmacokinetic profile of cetagliptin in healthy subjects. Both rapid absorption and prolonged duration demonstrate the potential value of cetagliptin for diabetes treatment.

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Duration of Diabetes and Cardiorenal Efficacy of Liraglutide and Semaglutide: A Post Hoc Analysis of the Leader and Sustain-6 Clinical Trials

Cited by 3 publications

References 11 publications

Primary versus secondary cardiorenal prevention in type 2 diabetes: Which newer anti‐hyperglycaemic drug matters?

Primary versus secondary cardiorenal prevention in type 2 diabetes: Which newer anti‐hyperglycaemic drug matters?

Heterogeneity amongst GLP-1 RA cardiovascular outcome trials results: can definition of established cardiovascular disease be the missing link?

Development and validation of an ultrasensitive LC–MS/MS method for the quantification of cetagliptin in human plasma and its application in a microdose clinical trial

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