The Landscape of Glucose-Lowering Therapy and Cardiovascular Outcomes: From Barren Land to Metropolis

Table 1

Summary of the completed trials of hypoglycemic therapy and cardiovascular outcome as a result of the 2008 FDA mandate.

Trial	Tested molecule	Comparator	Population	N	Duration; (years)	Primary outcome	Hazard ratio
ORIGIN [71]	Glargine	Standard care	Prediabetes or T2D with CV risk	12537	6.2	3-point MACE	1.02 (0.94–1.11)
DEVOTE [72]	Degludec	Glargine	T2D and above 50 years with CV or renal, or above 60 years at risk	7637	2.0	3-point MACE	0.91 (0.78 to 1.06)
SAVOR [41]	Saxagliptin	Placebo	T2D and above 40 with CV disease or above 55 years at risk	16492	2.1	3-point MACE	1.00 (0.89–1.12)
EXAMINE [43]	Alogliptin	Placebo	T2D and acute coronary syndrome within 15-90 days	5380	1.5	3-point MACE	0.96 (≤1.16)
TECOS [44]	Sitagliptin	Placebo	T2D and above 50 years and established CV disease	14671	3.0	4-point MACE	0.98 (0.88–1.09)
ELIXA [56]	Lixisenatide	Placebo	T2D and patients with acute coronary syndrome within 180 days	6068	2.1	3- point MACE	1.02 (0.89–1.17)
EMPA-REG [67]	Empagliflozin	Placebo	T2D and age above 18 years with established CV disease	7020	3.1	3-point MACE	0.86 (0.74–0.99)
CANVAS [62]	Canagliflozin	Placebo	T2D and age above 30 years with CV or above 50 years with ≥ 2 risks	10142	3.6	3- point MACE	0.86 (0.75 to 0.97)
LEADER [57]	Liraglutide	Placebo	T2D and age above 50 years and CV disease or above 60 years at risk	9340	3.8	3-point MACE	0.87 (0.78–0.97)
SUSTAIN-6 [58]	Semaglutide	Placebo	T2D and above 50 years with CV disease or age above 60 years at risk	3297	2.1	3- point MACE	0.86 (0.74–0.99)
ACE [88]	Acarbose	Placebo	IGT and above 50 years with CV disease	6522	5.0	5-point MACE	0.98 (0.86–1.11)
EXSCEL [89]	Exenatide	Placebo	T2D adults with established CV disease 70% or at risk 30%	14752	3.2	3-point MACE	0.91 (0.83–1.00)

Notes. Overall, study population across studies represents a high cardiovascular risk, with average age ranging from 60 to 65 years (±SD 7–10 years), mean BMI range is from 28.7 to 32.8 kg/m², with diabetes duration ranging between 5.4 and 13.8 years, and average HbA1C range is from 6.4 to 8.7% (±0.8–1.5%). Table adapted from Table from [2].