Do GLP‐1RAs and SGLT‐2is reduce cardiovascular events in black patients with type 2 diabetes? A systematic review and meta‐analysis

Mishriky, Basem M.; Powell, J.R.; Wittwer, Jennifer; Chu, Jennifer; Sewell, Kerry; Wu, Qiang; Cummings, Doyle M.

doi:10.1111/dom.13805

Cited by 27 publications

(26 citation statements)

References 56 publications

(206 reference statements)

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“…We used two previously performed and published literature searches to explore and include trials. 13,14 In addition, we searched review articles that examined completed and ongoing cardiovascular outcome trials. 15 Two Relative risks (RRs) with 95% confidence intervals (CIs) were used to summarize dichotomous data.…”

Section: Methodsmentioning

confidence: 99%

Sodium‐glucose co‐transporter‐2 inhibitors and atrial fibrillation in the cardiovascular and renal outcome trials

Okunrintemi

Mishriky

Powell

et al. 2020

Diabetes Obesity Metabolism

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Dapagliflozin is a sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor that has recently been shown to reduce the incidence of reported episodes of atrial fibrillation (AF)/atrial flutter in the DECLARE‐TIMI 58 trial. This raises the question regarding whether SGLT2 inhibitors can reduce the incidence of AF in a high‐risk population. We searched for trials comparing SGLT2 inhibitors to placebo in high‐risk individuals with or without diabetes (ie, cardiovascular and renal outcome trials) and that reported the incidence of AF as a serious adverse event. The EMPA‐REG OUTCOME trial, CANVAS, CANVAS‐R, the DECLARE‐TIMI 58 trial, CREDENCE, DAPA‐HF, VERTIS‐CV and DAPA‐CKD were included. The incidence of AF, reported as a serious adverse event, was 0.9% in individuals who received an SGLT2 inhibitor compared to 1.1% in those who received placebo. Pooled results showed a significantly lower incidence of AF in individuals with and without diabetes (relative risk 0.79, 95% confidence interval 0.67,0.93). This review suggests that there is a significantly lower risk of incident AF for individuals on SGLT2 inhibitors versus placebo. While there was a statistically significant lower incidence of AF, reported as a serious adverse event, more research is needed to evaluate its clinical significance.

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Section: Methodsmentioning

confidence: 99%

Sodium‐glucose co‐transporter‐2 inhibitors and atrial fibrillation in the cardiovascular and renal outcome trials

Okunrintemi

Mishriky

Powell

et al. 2020

Diabetes Obesity Metabolism

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“…While stratification of participants according to race or ethnic groups have not identified significant differences in the cardiovascular efficacy of GLP-1RAs, [6][7][8][9] given the under-representation of these populations in CVOTs, it is currently unclear whether GLP-1RAs reduce cardiovascular risk in specific race/ethnic groups (eg, black patients). 62 Moreover, it is unknown whether this under-representation in RCTs affects routine clinical practice and GLP-1RAs prescription. In this context, RWS have shown how subjects belonging to minorities have lower probability to achieve appropriate glucose control and control of other cardiovascular risk factors.…”

Section: Effectiveness In Special Populationsmentioning

confidence: 99%

<p>Long-Acting Injectable GLP-1 Receptor Agonists for the Treatment of Adults with Type 2 Diabetes: Perspectives from Clinical Practice</p>

Morieri

Avogaro

Fadini

2020

DMSO

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Randomized controlled trials (RCTs) have consistently shown glycemic and extra-glycemic benefits of long-acting injectable glucagon-like-peptide-1 receptor agonists (GLP-1RAs, liraglutide, albiglutide, exenatide once-weekly, dulaglutide, and semaglutide) in terms of reduction in the rates of cardiovascular events and mortality among patients with type 2 diabetes. Recently, the analyses of large datasets collecting routinely-accumulated data from clinical practice (ie, real-world studies, RWS) have provided new opportunities to complement the information obtained from RCTs. In this narrative review, we addressed clinically relevant questions that might be answered by well-conducted RWS: are subjects treated with GLP-1RAs in the "real-world" similar to those included in RCTs? Is the performance of GLP-1RA observed in the RWS (effectiveness) similar to that described in RCTs (efficacy)? Is the effectiveness similar in population of patients generally underrepresented in RCTs? Are the cardiovascular benefits of GLP-1RAs confirmed in RWS? We also describe a few comparisons currently un-explored by specific RCTs, such as direct comparison between different administration strategies (eg, fixed-versus flexiblecombination with basal-insulin) or between GLP-1RAs versus dipeptidyl-peptidase-4 inhibitor (DDP4i) or versus sodium/glucose cotransporter-2 inhibitors (SGLT-2i) on hard cardiorenal outcomes. Altogether, RWS provide highly informative information on treatment with GLP-1RAs. On the one side, RWS showed different clinical characteristics between subjects enrolled in RCTs versus those attending real-world clinics and receiving a GLP-1RA. On the other hand, RWS showed that GLP-1RA effectiveness is overall consistent in subgroups of patients less represented in RCTs. In addition, RWS allowed the identification of modifiable factors (eg, titration or adherence) that might guide physicians towards better GLP-1RAs use. Finally, multiple RWS reported better cardio-renal outcomes with GLP-1RAs than with DPP-4i, while initial findings from RWS described a weaker cardiovascular protection compared to SGLT-2i. Therefore, there is the need for further RWS and RCTs comparing these different classes of glucose lowering medications.

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“…In fact, most of the randomized clinical trials evaluating cardiometabolic risk factor control and long-term cardiovascular and mortality risk among patients with type 2 diabetes are primarily based on white patients, with marginal representation of black populations. 17 The meta-analysis of cardiovascular outcome trials evaluating GLP-1RAs and SGLT2 inhibitors by Hoppe et al 17 and Mishriky et al 18 reported that less than 5% of the trial populations were black, and only two of these trials collected race data consistent with US Food and Drug Administration (FDA) guidelines.…”

Section: Introductionmentioning

confidence: 99%

Cardiometabolic risk factor control in black and white people in the United States initiating sodium‐glucose co‐transporter‐2 inhibitors: A real‐world study

Montvida

Verma

Shaw

et al. 2020

Diabetes Obesity Metabolism

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Aims: To explore cardiometabolic risk profiles, the probability of sustainable control, and the effectiveness of treatment with sodium-glucose co-transporter-2 (SGLT2) inhibitors in black and white adults in the United States with type 2 diabetes. Materials and Methods: Using nationally representative US electronic medical records, 72 690 white and 10 004 black adults diagnosed with type 2 diabetes initiating SGLT2 inhibitors during the period 2013 to 2018, continuing it for ≥6 months, and with follow-up of ≥12 months, were identified. Glycated haemoglobin (HbA1c), body weight, systolic blood pressure (SBP) and lipid changes at 6 months, and sustainability of control over 18 months post SGLT2 inhibitor initiation were explored, separately in those with and without atherosclerotic cardiovascular disease (ASCVD). Results: The white group was older (58 years) with lower mean HbA1c (8.5%), compared to the black group (age 54 years, HbA1c 9.0%). Body mass index distribution was similar. The proportions of people with uncontrolled SBP, LDL cholesterol, non-HDL cholesterol and triglyceride levels were 24%, 42%, 51% and 62%, respectively, in white patients, and 31%, 51%, 49% and 32%, respectively, in black patients. At 6-month follow-up white and black patients had similar adjusted reductions in HbA1c (1.1%), SBP (8-10 mmHg), LDL cholesterol (0.26-0.34 mmol / L) and body weight (1.1-1.4 kg). However, over 18 months' follow-up, compared to white patients, black patients were significantly less likely to achieve sustainable control in HbA1c (odds ratio [OR] 0.67, 95% confidence interval [CI] 0.63-0.72), body weight (OR 0.81, 95% CI 0.72-0.91), SBP (OR 0.67, 95% CI 0.61-0.74) and LDL cholesterol (OR 0.77, 95% CI 0.67-0.89). Triglyceride control was significantly better among black patients. Black patients had a significantly higher risk factor burden, irrespective of ASCVD status. Conclusions: While the effectiveness of SGLT2 inhibitors was similar among black and white patients, irrespective of ASCVD status, black patients continued to have worse cardiometabolic risk factor burden after SGLT2 inhibitor initiation.

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Do GLP‐1RAs and SGLT‐2is reduce cardiovascular events in black patients with type 2 diabetes? A systematic review and meta‐analysis

Cited by 27 publications

References 56 publications

Sodium‐glucose co‐transporter‐2 inhibitors and atrial fibrillation in the cardiovascular and renal outcome trials

Sodium‐glucose co‐transporter‐2 inhibitors and atrial fibrillation in the cardiovascular and renal outcome trials

<p>Long-Acting Injectable GLP-1 Receptor Agonists for the Treatment of Adults with Type 2 Diabetes: Perspectives from Clinical Practice</p>

Cardiometabolic risk factor control in black and white people in the United States initiating sodium‐glucose co‐transporter‐2 inhibitors: A real‐world study

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