Nearly 100,000 patient data PK: in the prevention and treatment of MACE of diabetic patients, who is the most powerful among the three new hypoglycemic drugs?

Older adults with type 2 diabetes (T2D) have an increased
risk of cardiovascular disease (CVD) compared to older adults without T2D.
Although professional associations recommend two classes of glucose-lowering drugs, sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA), adopting these guidelines in routine care remains a challenge because evidence suggests that their cardiovascular benefits may not be consistent
among patient subgroups.

However, evidence on the efficacy of empagliflozin compared with alternative second-line hypoglycemic agents in T2D patients receiving usual care and with extensive cardiorenal risk remains limited
.

Therefore, this study compared the correlation
of empagliflozin (increased in recent years) with (1) liraglutide (the most commonly used GLP-1RA, demonstrated cardiovascular benefit), and (2) sitagliptin (the most commonly used drug in another glucose-lowering drug class of dipeptidyl peptidase-4 [DPP-4] inhibitors, which has demonstrated no cardiovascular effect).

This retrospective study included a total of 45,788 patients (22,894 pairs started treatment with empagliflozin or liraglutide matched by propensity score) and cohort 2 included 45,624 patients (22 812 pairs of propensity score-matched treatment started with empagliflozin or sitagliptin).

Primary outcomes were (1) modification of major cardiovascular adverse events (MACEs), including a combination of myocardial infarction, stroke and all-cause mortality, and (2) hospitalization for heart failure (HHF).

Results showed that of the 45,788 patients in cohort 1, the mean age was 71.
9 years (5.
1), 23,396 (51.
1%) were female, and 22,392 (48.
9%)
were male.
In 245624 cohort patients, the mean (SD) age was 72.
1 (5.
1) years; 21,418 cases (46.
9%) were females and 24,206 cases (53.
1%) were males
.

Patients with empagluflozin had a similar risk of MACE outcomes compared with patients with liraglutide (HR, 0.
90; 95% CI, 0.
79-1.
03), while the risk of HHF was reduced (HR, 0.
66; 95% CI,0.
52-0.
82)
。 In subgroups, empagliflozin was associated with the MACE outcome of patients with a history of ASCVD compared with liraglutide (HR, 0.
83; 95% CI, 0.
71-0.
98) and HF (HR, 0.
77; 95% CI, 0.
60 to 1.
00) risk was associated and estimated potential heterogeneity was observed by sex (male: HR, 0.
85 [95% CI, 0.
71 to 1.
01]; Women: HR, 1.
16 [95% CI, 0.
94-1.
42]; Homogeneity P = .
02).

However, a reduced risk of HHF was observed in most subgroups (e.
g.
, ASCVD: HR, 0.
66 [95% CI, 0.
51-0.
85]; HF：HR，0.
66 [95% CI，0.
49-0.
88]）
。

Empagliflozin was associated with a reduced risk of MACE outcomes (HR, 0.
68, 95% CI, 0.
60 to 0.
77) and HHF (HR, 0.
45, 95% CI, 0.
36 to 0.
56) compared to sitagliptin, and these results were consistent across
all subgroups 。 In patients with a history of ASCVD, empagliflozin has a greater absolute benefit over sitagliptin (MACE:RD, −17.
6 [95% CI, −24.
9 to -10.
4]; HHF: RD, −16.
7 [95% CI, −21.
7 to −11.
9]), HF(MACE: RD, −41.
1 [95% CI, −59.
9 to −22.
6]; HFF: RD, −50.
4 [95% CI, −67.
5 to −33.
9]), or CKD (MACE:RD, −26.
7 [95% CI, −41.
3 to −12.
3]; HHF: RD, −31.
9 [95% CI, −43.
5 to −20.
8]).

Overall, in this comparative study of efficacy in older adults, empagliflozin was associated with a lower risk of HHF (versus liraglutide and sitagliptin) and MACE outcomes (relative to sitagliptin), with a large absolute benefit
in patients with confirmed cardiorenal disease.
These findings suggest that older patients with T2D may benefit more from empagliflozin in terms of HHF risk compared with liraglutide or sitagliptin; Regarding the risk of MACE, empagliflozin may be superior to liraglutide only in patients with a history of cardiovascular disease and sitagliptin
in all patient subgroups.

Original source:

Htoo PT, Tesfaye H, Schneeweiss S, et al.
Comparative Effectiveness of Empagliflozin vs Liraglutide or Sitagliptin in Older Adults With Diverse Patient Characteristics.
JAMA Netw Open.
2022; 5(10):e2237606.
doi:10.
1001/jamanetworkopen.
2022.
37606