Highlights
- •Cardiovascular disease (CVD) is a primary cause of morbidity and mortality in type II diabetes mellitus.
- •CVD prevention/treatment is not used to select antihyperglycemic medications.
- •A new treatment algorithm based on the presence or risk of CVD and/or heart failure is needed.
- •Newer antihyperglycemic therapies can reduce CVD events.
Abstract
Patients with diabetes mellitus have increased rates of atherosclerotic cardiovascular
disease (CVD) and heart failure (HF). This increase occurs despite optimal lipid-lowering
therapies. We reviewed clinical trials of diabetes treatments and their effects on
circulating plasma lipoproteins and CVD. Several earlier studies failed to demonstrate
clear CVD benefit from diabetes therapies. In addition, triglyceride-reducing agents
did not reduce overall CVD in large clinical trials although these trials were not
conducted in cohorts selected as hypertriglyceridemic. Specific classes such as the
thiazolidinediones increased HF. After Food and Drug Administration mandates for more
rigorous safety data, recent studies have not only demonstrated CVD safety for many
diabetes mellitus agents, but have also shown that certain newer medications such
as empagliflozin, canagliflozin, liraglutide, and semaglutide reduce CVD. Moreover,
pioglitazone use in insulin-resistant patients has resulted in decreased cerebrovascular
and cardiovascular events, suggesting a protective vascular effect of this agent.
Benefits from these newer classes of medications are unlikely to be because of improved
lipoprotein profiles. These disparities in diabetes medication effects on CVD are
likely attributable to each drug or drug class' cardiometabolic effects. Selecting
medications based solely on their potential to lower hemoglobin A1C is an outdated
therapeutic approach. We propose a new algorithm for treatment of patients with type
II diabetes such that medication selection is based on the presence or risk of coronary
artery disease and/or HF.
Keywords
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References
- Metformin: non-glycemic effects and potential novel indications.Endocr Pract. 2016; 22: 999-1007
- Comparison of clinical outcomes and adverse events associated with glucose-lowering drugs in patients with type 2 diabetes: a meta-analysis.JAMA. 2016; 316: 313-324
- Liraglutide and cardiovascular outcomes in type 2 diabetes.N Engl J Med. 2016; 375: 311-322
- Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes.N Engl J Med. 2015; 373: 2117-2128
- Semaglutide and cardiovascular outcomes in patients with type 2 diabetes.N Engl J Med. 2016; 375: 1834-1844
- Comparison of quantity of left ventricular scarring and remodeling by magnetic resonance imaging in patients with versus without diabetes mellitus and with coronary artery disease.Am J Cardiol. 2011; 107: 1575-1578
- Lipid use and misuse by the heart.Circ Res. 2016; 118: 1736-1751
- High-density lipoprotein cholesterol in diabetes: is higher always better?.J Clin Lipidol. 2011; 5: 387-394
- Basal insulin and cardiovascular and other outcomes in dysglycemia.N Engl J Med. 2012; 367: 319-328
- Intensive glucose-lowering therapy reduces cardiovascular disease events in veterans' affairs diabetes trial participants with lower calcified coronary atherosclerosis.Diabetes. 2009; 58: 2642-2648
- The duration of diabetes affects the response to intensive glucose control in type 2 subjects: the VA diabetes trial.J Diabet Complications. 2011; 25: 355-361
- Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease.Diabetes Care. 2013; 36: 1304-1311
- Effect of glucagon-like peptide-1 receptor agonists on lipid profiles among type 2 diabetes: a systematic review and network meta-analysis.Clin Ther. 2015; 37 (e228): 225-241
- GLP-1 receptor agonist promotes brown remodeling in mouse white adipose tissue through SIRT1.Diabetologia. 2016; 59: 1059-1069
- Exenatide protects against glucose- and lipid-induced endothelial dysfunction: evidence for direct vasodilation effect of GLP-1 receptor agonists in humans.Diabetes. 2015; 64: 2624-2635
- Lixisenatide in patients with type 2 diabetes and acute coronary syndrome.N Engl J Med. 2015; 373: 2247-2257
- Effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction: a randomized clinical trial.JAMA. 2016; 316: 500-508
- SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials.Diab Vasc Dis Res. 2015; 12: 90-100
- Efficacy and safety of canagliflozin in patients with type 2 diabetes: a meta-analysis of randomized controlled trials.Medicine (Baltimore). 2016; 95: e5473
- Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME trial.Eur Heart J. 2016; 37: 1526-1534
- Insulin resistance as a physiological defense against metabolic stress: implications for the management of subsets of type 2 diabetes.Diabetes. 2015; 64: 673-686
- CV protection in the EMPA-REG OUTCOME Trial: a “thrifty substrate” hypothesis.Diabetes care. 2016; 39: 1108-1114
- Pharmacologic management of type 2 diabetes: 2016 interim update.Can J Diabetes. 2016; 40: 193-195
- Novel oral glucose-lowering drugs compared to insulin are associated with lower risk of all-cause mortality, cardiovascular events and severe hypoglycemia in type 2 diabetes patients.Diabetes Obes Metab. 2017; 19: 831-841
- Pioglitazone after ischemic stroke or transient ischemic attack.N Engl J Med. 2016; 374: 1321-1331
- Heart failure events with rosiglitazone in type 2 diabetes: data from the record clinical trial.Eur Heart J. 2010; 31: 824-831
- The effects of sulfonylureas plus metformin on lipids, blood pressure, and adverse events in type 2 diabetes: a meta-analysis of randomized controlled trials.Endocrine. 2013; 44: 648-658
- Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus.N Engl J Med. 2013; 369: 1317-1326
- Alogliptin after acute coronary syndrome in patients with type 2 diabetes.N Engl J Med. 2013; 369: 1327-1335
- Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes.N Engl J Med. 2015; 373: 232-242
- Empagliflozin and progression of kidney disease in type 2 diabetes.N Engl J Med. 2016; 375: 323-334
- Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomized, controlled trial.Ann Intern Med. 2016; 165: 305-315
Article info
Publication history
Published online: July 22, 2017
Accepted:
July 7,
2017
Received:
February 12,
2017
Identification
Copyright
© 2017 National Lipid Association. All rights reserved.
