Key result
SGLT2 inhibitors and GLP1 receptor agonists reduce MACE in multiple racial groups but not Black patients.
Why the study?
The cardiorenal protective effects of SGLT2 inhibitors and GLP-1 receptor agonists across different racial and ethnic groups were not well defined.
Do SGLT2 inhibitors and GLP1 receptor agonists reduce cardiovascular and renal events consistently across different racial, ethnic, and regional groups of patients with type 2 diabetes?
Meta-Analysis
Double-blind
Randomized
Yes
Do SGLT2 inhibitors and GLP1 receptor agonists reduce cardiovascular and renal events consistently across different racial, ethnic, and regional groups of patients with type 2 diabetes?
Hazard Ratio: 0.92 (95% CI 0.86–0.98)
SGLT2 inhibitors and GLP-1 receptor agonists provide consistent cardiorenal benefits in White and Asian populations with type 2 diabetes, but current evidence fails to demonstrate similar benefits in Black populations, highlighting a critical need for diverse trial recruitment.
OBJECTIVES: The cardiorenal protective effects of sodium-glucose co-transporter 2 inhibitors (SGLT2-Is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) across racial and ethnic groups are not well defined. By conducting a systematic review and meta-analysis of all randomised, placebo-controlled, cardiovascular disease (CVD) outcomes trials (CVOTs), we aimed to compare racial/ethnic as well as regional patterns in the effects of SGLT2-Is and GLP1-RAs on cardiovascular and renal outcomes in patients with type 2 diabetes (T2D). DESIGN: Trials were identified from MEDLINE, Embase, the Cochrane Library, and search of bibliographies to 7 July 2023. Setting North America, South/Central America, Europe (Eastern and Western), Asia, Australia-New Zealand (Pacific), Asia/Pacific, and Africa. SETTING: North America, South/Central America, Europe (Eastern and Western), Asia, Australia-New Zealand (Pacific), Asia/Pacific, and Africa. PARTICIPANTS: people with type 2 diabetes enrolled in cardiovascular outcome trials of SGLT2-Is and GLP1-RAs. MAIN OUTCOME MEASURES: Outcomes were (i) major adverse cardiovascular events (MACE), (ii) composite CVD death/heart failure (HF) hospitalization; (iii) composite renal outcome; and (iv) their components. Study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled. RESULTS: In total, 14 unique CVOTs (7 comparing SGLT2-Is vs placebo and 7 comparing GLP1-RAs vs placebo) were eligible. The proportion of participants enrolled in the trials ranged from 66.6-93.2% for White populations, 1.2-21.6% for Asian populations, 2.4-8.3% for Black populations and 0.9-23.1% for Other populations. The HR (95% CI) for MACE comparing SGLT2-Is vs placebo was 0.92 (0.86-0.98), 0.69 (0.53-0.92) and 0.70 (0.54-0.91) for White, Asian and Hispanic/Latino populations, respectively. Comparing GLP1-RAs vs placebo, the corresponding HR (95% CI) was 0.88 (0.80-0.97), 0.76 (0.63-0.93) and 0.82 (0.70-0.95), respectively. SGLT2-Is reduced the risk of all other cardiorenal outcomes in White and Asian populations, except for HF hospitalizations in Asians. No effects were observed in Black populations except for a reduced risk of HF hospitalizations by SGLT2-I. SGLT1-Is reduced the risk of composite CVD death/HF hospitalization in North America and Europe, whereas GLP1-RAs reduced the risk of MACE in Europe. GRADE certainty of evidence ranged from moderate to high. CONCLUSIONS: There appears to be substantial racial/ethnic differences in the cardiorenal effects of SGLT2-Is and GLP1-RAs in patients with T2D, with consistent benefits observed among White and Asian populations and consistent lack of benefits in Black populations. Whether the differences are due to issues with under-representation of Black populations and low statistical power or racial/ethnic variations in the pharmacokinetics, pharmacodynamics and safety of SGLT2-Is and GLP1-RAs need further investigation.PROSPERO Registration: CRD42023401734.
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Kunutsor et al. (2023) conducted a meta-analysis in Type 2 diabetes. Sodium-glucose co-transporter 2 inhibitors (SGLT2-Is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) vs. Placebo was evaluated on Major adverse cardiovascular events (MACE) comparing SGLT2-Is vs placebo in White populations (HR 0.92, 95% CI 0.86-0.98). SGLT2 inhibitors and GLP1 receptor agonists reduced the risk of major adverse cardiovascular events in White, Asian, and Hispanic/Latino populations with type 2 diabetes, but showed no consistent benefit in Black populations.
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