Update on evidence-based clinical application of sodium-glucose cotransporter inhibitors: Insight to uncommon cardiovascular disease scenarios in diabetes

Table 4 Summary of clinical studies on sodium-glucose co-transporter inhibitors in primary prevention of atherosclerotic cardiovascular disease/cardiovascular disease patients

Ref.	Type of article	Journal and published time	Drugs	Aim of study	Inclusive population	Intervention cycle	Number of cases	Main conclusion
Katakami et al[39]	RCT	Cardiovasc Diabetol, 2020	Tofogliflozin (20 mg/d in addition to an alternative antidiabetic agent), or placebo	To investigate the preventive effects of tofogliflozin on atherosclerosis in T2D patients without apparent cardiovascular disease by monitoring carotid intima-media thickness	Patients with T2D and no history of apparent cardiovascular disease	104 wk	340	Tofogliflozin is a safe and effective treatment option for managing primary cardiovascular disease risk factors in this population
Kosiborod et al[40]	RCT	J Am Coll Cardiol, 2018	Dapagliflozin (2.5/5/10 mg/d), canagliflozin (100/300 mg/d), empagliflozin (10/25 mg/d), ipragliflozin (50 mg/d), tofogliflozin (20 mg/d), luseogliflozin (2.5 mg/d), or oGLD	To examine a broad range of cardiovascular outcomes in patients initiated on SGLT2is vs oGLD across 6 countries in the Asia Pacific, the Middle East, and North American regions	Patients initiated on SGLT2is vs oGLD	Start date ranged from December 2013 in Australia to April 2015 in Israel, last date of data collection from June 2016 in Australia to November 2017 in Singapore1	235064	SGLT2is were associated with a lower risk of cardiovascular events across a broad range of outcomes and patient characteristics
Zelniker et al[41]	Meta-analysis	Lancet, 2019	Empagliflozin (10/25 mg/d), canagliflozin (100/300 mg/d), dapagliflozin (10 mg/d), or placebo	To evaluate the magnitude of effect of SGLT2is on specific cardiovascular and renal outcomes and whether heterogeneity is based on key baseline characteristics	Patients with T2D	2.4-4.2 years	34322	SGLT2is have moderate benefits on atherosclerotic MACEs that seem confined to patients with established atherosclerotic cardiovascular disease
Rahman et al[42]	Meta-analysis	J Am Heart Assoc, 2023	Dapagliflozin (10 mg/d), canagliflozin (100 mg/d), sotagliflozin (400 mg/d), or placebo	To explore the benefit in patients without established ASCVD	Patients with prior ASCVD and T2D	69-218 wk	23987	SGLT2is significantly reduced atherosclerotic MACEs in both CKD and T2D without established ASCVD
Giugliano et al[43]	Meta-analysis	Diabetes Obes Metab, 2021	Dapagliflozin (2.5/5/10 mg/d), canagliflozin (100/300 mg/d), empagliflozin (10/25 mg/d), ertugliflozin (5/15 mg/d), sotagliflozin (200/400 mg/d), or placebo	To present a meta-analysis of cardiorenal outcomes of SGLT2is available in Europe or the United States in patients with T2D	Patients with T2D	1.5-4.2 years	65587	SGLT2is have moderate benefits on MACEs and major benefits on the progression of diabetic kidney disease

¹Patients were followed from index date (initiation of either sodium-glucose co-transporter-2 inhibitors or other glucose-lowering drugs) until end of the index treatment (on-treatment analysis only), migration/leaving the practice/database, last date of data collection, outcome date, or censoring date.

CKD: Chronic kidney disease; MACEs: Major adverse cardiovascular events; oGLD: Other glucose-lowering drugs; SGLT2i: Sodium-glucose co-transporter-2 inhibitors; T2D: Type 2 diabetes.