The Easy and Prompt Access to Research Results for Patients vs. the Premature Incorporation of New Drugs
Type 2 diabetes mellitus (T2DM) is a common and increasingly prevalent disease and represent a major public health worldwide. People with diabetes have increased risk of serious health complications including vision loss, kidney failure, vascular complications such as myocardial infarction and stroke, and premature death.
Editorial
Type 2 diabetes mellitus (T2DM) is a common and increasingly prevalent disease and represent a major public health worldwide. People with diabetes have increased risk of serious health complications including vision loss, kidney failure, vascular complications such as myocardial infarction and stroke, and premature death [1, 2]. Good glycemic control remains the main foundation of T2DM treatment, this approach play a role in preventing or delaying the onset and progression of diabetic complications. Among diabetes-related complications, cardiovascular disease (CVD) is a leading cause of mortality and adverse outcomes in people with T2DM [1]. However, despite the clear correlation between diabetes and negative CV outcomes, it is still not clear whether glycemic control per se would have any effect on reducing CVD in T2DM patients [3, 4, 5]. Before 2008 US Food and Drug Administration (FDA) and 2012 European Medicines Agency (EMA) regulations, few trials of glucose-lowering drugs or strategies in people with type 2 diabetes have investigated cardiovascular outcomes, even though most patients die from cardiovascular causes despite the beneficial effects of lipid-reducing and blood pressure-lowering treatments. Since these dates FDA and EMA requirement that all new therapies for diabetes undergo a rigorous assessment of CV safety through large-scale cardiovascular outcome trials (CVOT). FAD guidelines include, among others:
- Patient selection should focus on high risk populations, including those with advanced disease, elderly and those with renal impairment.
- Trials must include at least 2 years of CV safety data, and
- A prospective independent adjudication of CV events in phase 2 and 3 studies must also be performed (CV events include, CV mortality, myocardial infarction, stroke and possibly hospitalization for acute coronary syndrome).
After FDA and EMA guidance request for the CV safety for new anti-diabetic drugs, 18 CVOT have been initiated. From those, results for seven are already available: SAVOR-TIMI53, EXAMINE, TECOS, ELIXA, EMPA-REG OUTCOME, LEADER, and SUSTAIN-
References
-
Gregg EW, Gu Q, Cheng YJ, Narayan KM, Cowie CC (2007) Mortality trends in men and women with diabetes, 1971 to 2000. Ann Intern Med 147(3): 149-155
-
Seshasai SR, Kaptoge S, Thompson A, Di Angelantonio E, Gao P, et al. (2011) Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Eng J Med 364(9): 829-841.
-
American Diabetes Association (2017) Pharmacological Approaches to Glycemic Treatment. Diabetes Care 40(S1): S64-S74.
-
Scheen AJ, Charbonnel B (2014) Effects of glucose lowering-agents on vascular outcomes in type 2 diabetes: a critical reappraisal. Diabetes Med 40(3): 176-185.
-
Holman RR, Sourij H, Califf RM (2014) Cardiovascular outcomes trials of glucose – lowering drugs or strategies in type 2 diabetes. Lancet 383(9933): 2008-2017.
-
Ferrenini E, DeFronzo RA (2015) Impact of glucose- lowering drugs on cardiovascular disease in type2 diabetes. Eur Heart J 36(34): 2288-2296.
-
Marso SP, Daniels GH, Brown FK, Kristensen P, Maan JF, et al. (2016) Liraglutide and cardiovascular outcomes in type 2 diabetes. N Eng J Med 375(4): 311-322.
-
Marso SP, Brain SC, Consoli A, Eliaschewitz FG, Jodar E, et al. (2016) Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Eng J Med 375(19): 1834-1844.
-
Fitchett D, Zinman B, Wanner C, Hantel S, Salsali AJ, et al. (2016) Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMP-REG OUTCOME trial. Eur Heart J 37(19): 1526-1534.
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