TY - JOUR
T1 - Cardiovascular effects of noninsulin, glucose-lowering agents
T2 - Need for more outcomes data
AU - Joshi, Parag H.
AU - Kalyani, Rita R.
AU - Blumenthal, Roger S.
AU - Donner, Thomas W.
PY - 2012/11/6
Y1 - 2012/11/6
N2 - Macrovascular complications of type 2 diabetes mellitus (DM) are primarily driven by the combination of underlying atherosclerosis and propensity for thrombosis. Prevention of macrovascular complications in DM relies on therapies directed at multiple coexisting intermediary pathophysiologies that contribute to cardiovascular events, including hyperglycemia, lipoprotein abnormalities, hypertension, inflammation, and propensity for thrombosis. Multiple noninsulin, glucose-lowering agents have been developed that effectively lower blood glucose levels. This review explores the literature on the cardiovascular benefits and harms associated with these therapies, with an emphasis on cardiovascular outcomes when available. The lack of long-term data on cardiovascular outcomes regarding safety and efficacy of available traditional glucose-lowering agents has led to recommendations for more thorough evaluations of new therapies before approval. Furthermore, recent data suggest harm from intensive hemoglobin A1c reductions. Accordingly, there are multiple, large, cardiovascular-event driven phase 3-4 trials of therapies from the incretin axis currently enrolling. Recommendations for a therapeutic approach with noninsulin, glucose-lowering agents for the prevention of cardiovascular events in patients with type 2 DM are provided based on current data. Ultimately, multifactorial risk interventions, including lifestyle modifications, antihyperglycemic agents, antihypertensives, statins, and aspirin remain the primary focus to prevent macrovascular complications in patients with type 2 DM.
AB - Macrovascular complications of type 2 diabetes mellitus (DM) are primarily driven by the combination of underlying atherosclerosis and propensity for thrombosis. Prevention of macrovascular complications in DM relies on therapies directed at multiple coexisting intermediary pathophysiologies that contribute to cardiovascular events, including hyperglycemia, lipoprotein abnormalities, hypertension, inflammation, and propensity for thrombosis. Multiple noninsulin, glucose-lowering agents have been developed that effectively lower blood glucose levels. This review explores the literature on the cardiovascular benefits and harms associated with these therapies, with an emphasis on cardiovascular outcomes when available. The lack of long-term data on cardiovascular outcomes regarding safety and efficacy of available traditional glucose-lowering agents has led to recommendations for more thorough evaluations of new therapies before approval. Furthermore, recent data suggest harm from intensive hemoglobin A1c reductions. Accordingly, there are multiple, large, cardiovascular-event driven phase 3-4 trials of therapies from the incretin axis currently enrolling. Recommendations for a therapeutic approach with noninsulin, glucose-lowering agents for the prevention of cardiovascular events in patients with type 2 DM are provided based on current data. Ultimately, multifactorial risk interventions, including lifestyle modifications, antihyperglycemic agents, antihypertensives, statins, and aspirin remain the primary focus to prevent macrovascular complications in patients with type 2 DM.
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U2 - 10.1016/j.amjcard.2012.08.030
DO - 10.1016/j.amjcard.2012.08.030
M3 - Article
C2 - 23062565
AN - SCOPUS:84867535853
SN - 0002-9149
VL - 110
SP - 32B-42B
JO - American Journal of Cardiology
JF - American Journal of Cardiology
IS - SUPPL. 9
ER -