Mark Warren, MD: When I’m evaluating a clinical trial for type 2 diabetes, I look at what the purpose of the trial was. If it’s cardiovascular outcome and cardiovascular safety, then I look at the secondary outcomes such as glycemic control, weight gain, and progression in renal disease. If I have an agent that actually can decrease cardiovascular risk and events, decrease the progression of nephropathy, have better glycemic control, and have weight loss instead of weight gain, those are all big wins. That’s important for me.

Recent cardiovascular outcome trials have been very important in determining what drugs we use for our patients. In the LEADER trial, we looked at comparing liraglutide to placebo in patients who are at high risk or who had had a cardiovascular event. There was about a 13% reduction in the composite endpoint over and beyond what we attained with conventional care, with statins, ACE inhibitors, and aspirin. So, this is over and beyond what we would expect from the statins. That’s extremely important—and an amazing finding—that we were able to improve upon the statin effect. Also, with the CANVAS trial using canagliflozin, there was also about a 14% reduction in the composite outcome, 3-point MACE, or major adverse cardiovascular events. So, it showed, with using that SGLT2 inhibitor in patients who either had an event or are at high risk for an event, that they were at lower risk with canagliflozin. They also had less progression and nephropathy in both the LEADER trial and with the canagliflozin, or the CANVAS trials. Those are very important findings that were able to show both a decrease in cardiovascular events and a decrease in the progression of nephropathy.

When evaluating the cardiovascular outcome trials, I look at what they found. Was it consistent in all the endpoints, such as with nonfatal MI, all-cause mortality, and strokes? Or, was it just in one of the areas that was it driven by, for example, strokes or heart attacks? Or, was it always consistent throughout the 3-point MACE. So, if something is more consistent across all 3 of those, that shows me it probably is more of an effect on the atherosclerotic events, and just a more consistent effect.

Looking at the cardiovascular outcomes trials, it’s important to me to look at all the results: not just the cardiovascular endpoints, but also the side effect profile and the tolerability, preferably weight loss versus weight gain and how often they’re able to maintain the medication and not stop it for fear of side effects or because of side effects.

Impact of Cardiovascular Data in Type 2 Diabetes

Mark Warren, MD, offers insight regarding the recent cardiovascular outcomes trials in type 2 diabetes.
Published Online: September 12, 2017


Mark Warren, MD: When I’m evaluating a clinical trial for type 2 diabetes, I look at what the purpose of the trial was. If it’s cardiovascular outcome and cardiovascular safety, then I look at the secondary outcomes such as glycemic control, weight gain, and progression in renal disease. If I have an agent that actually can decrease cardiovascular risk and events, decrease the progression of nephropathy, have better glycemic control, and have weight loss instead of weight gain, those are all big wins. That’s important for me.

Recent cardiovascular outcome trials have been very important in determining what drugs we use for our patients. In the LEADER trial, we looked at comparing liraglutide to placebo in patients who are at high risk or who had had a cardiovascular event. There was about a 13% reduction in the composite endpoint over and beyond what we attained with conventional care, with statins, ACE inhibitors, and aspirin. So, this is over and beyond what we would expect from the statins. That’s extremely important—and an amazing finding—that we were able to improve upon the statin effect. Also, with the CANVAS trial using canagliflozin, there was also about a 14% reduction in the composite outcome, 3-point MACE, or major adverse cardiovascular events. So, it showed, with using that SGLT2 inhibitor in patients who either had an event or are at high risk for an event, that they were at lower risk with canagliflozin. They also had less progression and nephropathy in both the LEADER trial and with the canagliflozin, or the CANVAS trials. Those are very important findings that were able to show both a decrease in cardiovascular events and a decrease in the progression of nephropathy.

When evaluating the cardiovascular outcome trials, I look at what they found. Was it consistent in all the endpoints, such as with nonfatal MI, all-cause mortality, and strokes? Or, was it just in one of the areas that was it driven by, for example, strokes or heart attacks? Or, was it always consistent throughout the 3-point MACE. So, if something is more consistent across all 3 of those, that shows me it probably is more of an effect on the atherosclerotic events, and just a more consistent effect.

Looking at the cardiovascular outcomes trials, it’s important to me to look at all the results: not just the cardiovascular endpoints, but also the side effect profile and the tolerability, preferably weight loss versus weight gain and how often they’re able to maintain the medication and not stop it for fear of side effects or because of side effects.
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Episode 2 When to Start Insulin? Lack of Consensus on Targets
Episode 3 Comparing New Insulins to Older Formulations
Episode 4 Understanding Factors Behind Insulin Costs
Episode 5 Formulary Decisions and Clinical Practice
Episode 6 Glycemic Control Is the Bottom Line
Episode 7 The Advantages of Insulin, GLP-1 Combinations
Episode 8 Adherence Matters When Weighing a Single Injection
Episode 9 Juggling Multiple Factors When Selecting Therapy
Episode 10 Formulary Management: Antidiabetes Medications
Episode 11 Barriers to Traditional Insulin Therapy
Episode 12 Evidence With Ultra–Long Acting Insulins
Episode 13 Appropriate Access: Payer Perspective on Newer Insulins
Episode 14 Cardiovascular Considerations in Antidiabetic Therapies
Episode 15 Formulary Decisions and GLP-1/Insulin Combinations
Episode 16 Role of GLP-1/Insulin Combinations
Episode 17 Barriers to Insulin Therapy in Type 2 Diabetes
Episode 18 Practical Decisions in Type 2 Diabetes
Episode 19 Deciding Among Insulin Therapies for Type 2 Diabetes
Episode 20 Formulary Access to Insulins in Type 2 Diabetes
Episode 21 Clinical Evidence of Insulin Degludec in Type 2 Diabetes
Episode 22 Hypoglycemia: An Unrecognized Complication in Diabetes
Episode 23 Access to Therapeutic Combinations in Type 2 Diabetes
Episode 24 Impact of Cardiovascular Data in Type 2 Diabetes
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