The Lancet: Diabetics who derive the greatest cardiovascular benefit from SGLT2i and GLP-1 RA have these characteristics!

The cardiovascular (CV) benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) in patients with type 2 diabetes mellitus (T2D) are well documented and may extend
in certain risk groups.

For example, a meta-analysis examining sex differences found a significant reduction in major adverse CVE events (MACE) in men but not in women with SGLT2i, while for GLP-1 RA, pooled data showed a significant reduction in
MACE in both sexes.
However, the study did not directly compare data
for men and women.
Regarding racial disparities, a recent meta-analysis of ten cardiovascular outcome trials (CVOTs) showed a significant reduction in MACE among Asian participants with GLP-1 RA, but not
SGLT2i.
In addition, although black patients are more affected by cardiovascular disease (coronary heart disease and type 2 diabetes) and advanced kidney disease, and cardiovascular outcomes are more severe, in addition, the incidence of T2D increases with obesity and age
, as obesity plays a crucial role in the development and progression of T2D.

Currently, it is unclear whether the CV benefits of SGLT2i or GLP-1 RA are maintained
in blacks, the elderly, and obese diabetics.
Therefore, this study aims to provide an overall risk ratio (HR) estimate of MACE for SGLT2i and GLP-1 RA, by age (< 65 vs.
≥ 65 years and < 75 years vs.
≥ 75 years old), gender (male vs.
female), race (black vs.
white, black vs.
Asian, white vs.
Asian), body mass index (BMI: < 30 kg/m 2 vs.
≥ 30 kg/m²), and duration of diabetes (< 10 years vs.
≥ 10 years) stratified
by BMI.

In this report, a total of 11 studies met the pre-specified criteria, covering 96,580 patients with
T2D.
Of these patients, there were 61,975 (64.
2%) male, 34,605 (35.
8%) female, and ethnicity including 74,982 (77.
6%) white, 7,760 (8.
0%) Asian, and 4,023 (4.
2%) black
.
In two SGLT2i trials, the HR (95% CI) for long-term diabetes lasting more than 10 years versus short-term diabetes was 0.
84 (0.
77 to 0.
93) vs.
1.
02 (0.
89-1.
16) (interaction P = 0.
03).

In the four SGLT2i trials, the benefits of MACE were similar
in terms of sex (interaction P = 0.
13), age (interaction P = 0.
36), BMI (interaction P = 0.
69), and racial group (black and white interaction P = 0.
86, black and Asian interaction P = 0.
98, white and Asian interaction P = 0.
69).

For GLP-1 RAs, Asians tended to gain more MACE (0.
71, [0.
58-0.
87]) than whites (0.
87, [0.
81-0.
94]) (interaction P = 0.
07).

In two trials of GLP-1 RAs, MACE outcomes were reduced by 22% (0.
78, 0.
63 to 0.
95) in older patients (≥ 75 years), compared with no difference (0.
87; 0.
75 to 1.
01) in patients aged < 75 years (interaction P = 0.
37).

。 In the remaining risk groups, the benefits of MACE were in sex (interaction P = 0.
37), age, and age; Age< 65 years (interaction P = 0.
80), diabetes course (interaction P = 0.
70), race (black and white interaction P = 0.
57, black and Asian interaction P = 0.
15), BMI (interaction P = 0.
78) aspects are similar
.

SGLT2i was at low risk of bias for sex and overall heterogeneity, with I2 values ranging from 0% to 54% for the remaining comparisons, moderate to low
.

Overall, older patients and Asian patients with MACE received greater benefit from MACE compared with white patients with GLP-1 RAs and long-term diabetes with SGLT2i in patients with established cardiovascular disease or type 2 diabetes who were at highest risk of cardiovascular disease
.
These findings may help guide treatment prescribing and help inform the selection and stratification
of future patients with CVOTs.
In addition, there is an urgent need for pooled individual patient-level data to support this conclusion and obtain clear evidence
.

Original source:

Alhassane Diallo, Age, sex, race, BMI, and duration of diabetes differences in cardiovascular outcomes with glucose lowering drugs in type 2 diabetes: A systematic review and meta-analysis.
eClinicalMedicine 2022; 54: 101697 Published online xxx https://doi.
org/10.
1016/j.
eclinm.
2022.
101697