Subpopulation Differences in the Cardiovascular Efficacy of Long-Acting Glucagon-Like Peptide 1 Receptor Agonists in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

He, Liyun; Yang, Na; Xu, Lingling; Ping, Fan; Li, Wei; Li, Yuxiu; Zhang, Huabing

doi:10.1007/s13300-020-00882-2

Cited by 4 publications

(8 citation statements)

References 32 publications

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“… History of CVD 3 105 – 107 8 125 , 162 – 167 7 83 , 90 – 95 , 98 , 99 4 104 – 106 , 109 3 86 , 168 , 169 5 2 , 80 , 83 , 95 , 112 No consistent impact on SGLT2i or GLP1-RA outcomes. Age 2 107 , 108 3 121 , 165 , 170 3 83 , 92 , 94 2 104 , 109 1 171 4 78 – 80 , 83 No consistent heterogeneity by age for SGLT2is; No evidence of age effect for GLP1-RAs. Sex 3 102 , 107 , 108 1 165 5 83 , 90 , 92 , 94 , 96 , 99 4 102 , ...…”

Section: Resultsmentioning

confidence: 99%

Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors: a systematic review

Young,

McInnes,

Massey

et al. 2023

Commun Med

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Background A precision medicine approach in type 2 diabetes requires the identification of clinical and biological features that are reproducibly associated with differences in clinical outcomes with specific anti-hyperglycaemic therapies. Robust evidence of such treatment effect heterogeneity could support more individualized clinical decisions on optimal type 2 diabetes therapy. Methods We performed a pre-registered systematic review of meta-analysis studies, randomized control trials, and observational studies evaluating clinical and biological features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies, considering glycaemic, cardiovascular, and renal outcomes. After screening 5,686 studies, we included 101 studies of SGLT2-inhibitors and 75 studies of GLP1-receptor agonists in the final systematic review. Results Here we show that the majority of included papers have methodological limitations precluding robust assessment of treatment effect heterogeneity. For SGLT2-inhibitors, multiple observational studies suggest lower renal function as a predictor of lesser glycaemic response, while markers of reduced insulin secretion predict lesser glycaemic response with GLP1-receptor agonists. For both therapies, multiple post-hoc analyses of randomized control trials (including trial meta-analysis) identify minimal clinically relevant treatment effect heterogeneity for cardiovascular and renal outcomes. Conclusions Current evidence on treatment effect heterogeneity for SGLT2-inhibitor and GLP1-receptor agonist therapies is limited, likely reflecting the methodological limitations of published studies. Robust and appropriately powered studies are required to understand type 2 diabetes treatment effect heterogeneity and evaluate the potential for precision medicine to inform future clinical care.

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Section: Resultsmentioning

confidence: 99%

Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors: a systematic review

Young,

McInnes,

Massey

et al. 2023

Commun Med

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show abstract

“…A similar meta-analysis reported that the glucose-lowering effectiveness seemed to be similar among Asian people and people who are not Asian regardless of baseline weight 208 . Previous meta-analyses comparing cardiovascular risk reduction among Asian people and people who are not Asian reported mixed findings 209,210 , but an updated meta-analysis of six cardiovascular outcome trials for GLP1 receptor agonists reported that reductions in major adverse cardiovascular events were greater among Asian people than in white people 202 . Emerging evidence suggests that GLP1 receptor agonists could be more effective when initiated early in the course of disease among people with adequate β-cell function 211 .…”

Section: Glp1 Receptor Agonistsmentioning

confidence: 99%

Pathophysiology, phenotypes and management of type 2 diabetes mellitus in Indian and Chinese populations

et al. 2022

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| Nearly half of all adults with type 2 diabetes mellitus (T2DM) live in India and China. These populations have an underlying predisposition to deficient insulin secretion, which has a key role in the pathogenesis of T2DM. Indian and Chinese people might be more susceptible to hepatic or skeletal muscle insulin resistance, respectively, than other populations, resulting in specific forms of insulin deficiency. Cluster-based phenotypic analyses demonstrate a higher frequency of severe insulin-deficient diabetes mellitus and younger ages at diagnosis, lower β-cell function, lower insulin resistance and lower BMI among Indian and Chinese people compared with European people. Individuals diagnosed earliest in life have the most aggressive course of disease and the highest risk of complications. These characteristics might contribute to distinctive responses to glucose-lowering medications. Incretin-based agents are particularly effective for lowering glucose levels in these populations; they enhance incretin-augmented insulin secretion and suppress glucagon secretion. Sodium-glucose cotransporter 2 inhibitors might also lower blood levels of glucose especially effectively among Asian people, while α-glucosidase inhibitors are better tolerated in east Asian populations versus other populations. Further research is needed to better characterize and address the pathophysiology and phenotypes of T2DM in Indian and Chinese populations, and to further develop individualized treatment strategies.

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“…Analysis of these findings entails limitations that stem from the fact that results were based on adverse events reports and subsequent precise evaluation was not performed. Causal relationship between DR risk and the use of GLP-1 agonists was not confirmed in further meta-analyses [ 43 , 44 , 45 , 46 ]. In an AngioSafe study, designed to determine the safety of GLP-1 RAs in the retina, in both clinical models with liraglutide and experimental models with exenatide, negative effects on retinal angiogenesis and severe DR were not confirmed [ 47 ].…”

Section: Resultsmentioning

confidence: 97%

Will GLP-1 Analogues and SGLT-2 Inhibitors Become New Game Changers for Diabetic Retinopathy?

Wołos-Kłosowicz

Matuszewski

Rutkowska

et al. 2022

JCM

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Diabetic retinopathy (DR) is the most frequent microvascular complication of diabetes mellitus (DM), estimated to affect approximately one-third of the diabetic population, and the most common cause of preventable vision loss. The available treatment options focus on the late stages of this complication, while in the early stages there is no dedicated treatment besides optimizing blood pressure, lipid and glycemic control; DR is still lacking effective preventive methods. glucagon-like peptide 1 receptor agonists (GLP-1 Ras) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors have a proven effect in reducing risk factors of DR and numerous experimental and animal studies have strongly established its retinoprotective potential. Both drug groups have the evident potential to become a new therapeutic option for the prevention and treatment of diabetic retinopathy and there is an urgent need for further comprehensive clinical trials to verify whether these findings are translatable to humans.

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Subpopulation Differences in the Cardiovascular Efficacy of Long-Acting Glucagon-Like Peptide 1 Receptor Agonists in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

Cited by 4 publications

References 32 publications

Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors: a systematic review

Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors: a systematic review

Pathophysiology, phenotypes and management of type 2 diabetes mellitus in Indian and Chinese populations

Will GLP-1 Analogues and SGLT-2 Inhibitors Become New Game Changers for Diabetic Retinopathy?

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