In the Journals

DPP-IV inhibitors appear to reduce CV risk in type 2 diabetes

Unlike traditional oral diabetes medications, DDP-IV inhibitors have been associated with a decreased risk for cardiovascular events in patients with type 2 diabetes when used long term, according to data from a meta-analysis.

David S. H. Bell, MD, FACE, FACP, of Southside Endocrinology and University of Alabama Medical School in Birmingham and an Endocrine Today Editorial Board member, and colleagues said they found nearly a 60% decrease in CV events with DPP-IV inhibitors.

David S.H. Bell, MD, FACE, FACP 

David S.H. Bell

With DPP-IV therapy, the RR for any adverse CV event was 0.48 (95% CI, 0.31-0.75), and the RR for nonfatal MI or acute coronary syndrome was 0.4 (95% CI, 0.18-0.88).

“I think this is a turning point in the management of diabetes, from a cardiac standpoint, where we’ll consider not only glucose and HbA1c numbers, but also choose therapies that we can be confident improve CV prognosis,” James H. O’Keefe Jr., MD, of Saint Luke’s Mid America Heart Institute in Kansas City, told Endocrine Today of these findings.

“What a lot of physicians haven’t understood and really don’t believe, is that despite the fact that we’ve been treating diabetes for 70 or 80 years, and despite the fact that 70% of people with diabetes die from heart disease, our therapies for treating diabetes have not been shown to reduce the very high rate of CV death. All these mainstays of therapy we use to meticulously get their sugars down don’t seem to reduce heart attack and stroke and cardiac death, which is really the elephant in the room; we’ve sort of kind of ignored that reality.”

According to O’Keefe, in practice as a cardiologist, prognosis among patients with diabetes is not as promising as patients without diabetes. “I think it’s because we haven’t normalized the CVD risk,” he explained.

Promise of DPP-IV inhibition

The analysis included 18 trials of 4,998 patients randomly assigned to DPP-IV inhibitors and 3,546 to a comparative oral diabetes drug. A search of electronic databases identified trials published or unpublished in the literature until Sept. 30, 2011, that were at least 24 weeks.

Compared with placebo, the risk for adverse CV events was not significantly different with DPP-IV inhibitors (RR=1.05; 95% CI, 0.39-2.82); however, compared with metformin and other oral agents, including sulfonylureas and thiazolidinediones, the risk for CV events was significantly lower with DPP-IV inhibitor therapy (RR=0.42; 95% CI, 0.20-0.87 and RR=0.33; 95% CI, 0.16-0.67, respectively).

“It seems that DPP-IV inhibitors reduce cardiac events solely by lowering postprandial glucose; the same reductions have been shown with alfa-glucosidase inhibitors and quick-release bromocriptine-drugs which, by different mechanisms, only lower postprandial glucose. However, because DPP-IV is a ubiquitous enzyme involved in many other systems, it is possible that a non-metabolic action could explain the reduction in cardiac events. For example, DPP-IV inhibition increases the levels of HMGB1, a protein that increases angiogenesis and is deficient in patients with diabetes. Angiogenesis has been shown to be decreased in people with diabetes when compared with individuals without diabetes,” Bell told Endocrine Today.

Additionally, long-term use of DPP-IV inhibitors — specifically, trials at least 52 weeks — was associated with a lower risk for CV events compared with controls (RR=0.37; 95% CI, 0.21-0.63). However, this association was not observed in studies with less than 52 weeks of DPP-IV inhibitor treatment (RR=0.78; 95% CI, 0.38-1.60).

“This is all emerging data that needs to be confirmed, but both my clinical experience and work with these data make me pretty confident that we’re on the verge of a new era in treating diabetes that will be based on these incretin-based therapies,” O’Keefe said.

Unlike traditional oral diabetes medications, DDP-IV inhibitors have been associated with a decreased risk for cardiovascular events in patients with type 2 diabetes when used long term, according to data from a meta-analysis.

David S. H. Bell, MD, FACE, FACP, of Southside Endocrinology and University of Alabama Medical School in Birmingham and an Endocrine Today Editorial Board member, and colleagues said they found nearly a 60% decrease in CV events with DPP-IV inhibitors.

David S.H. Bell, MD, FACE, FACP 

David S.H. Bell

With DPP-IV therapy, the RR for any adverse CV event was 0.48 (95% CI, 0.31-0.75), and the RR for nonfatal MI or acute coronary syndrome was 0.4 (95% CI, 0.18-0.88).

“I think this is a turning point in the management of diabetes, from a cardiac standpoint, where we’ll consider not only glucose and HbA1c numbers, but also choose therapies that we can be confident improve CV prognosis,” James H. O’Keefe Jr., MD, of Saint Luke’s Mid America Heart Institute in Kansas City, told Endocrine Today of these findings.

“What a lot of physicians haven’t understood and really don’t believe, is that despite the fact that we’ve been treating diabetes for 70 or 80 years, and despite the fact that 70% of people with diabetes die from heart disease, our therapies for treating diabetes have not been shown to reduce the very high rate of CV death. All these mainstays of therapy we use to meticulously get their sugars down don’t seem to reduce heart attack and stroke and cardiac death, which is really the elephant in the room; we’ve sort of kind of ignored that reality.”

According to O’Keefe, in practice as a cardiologist, prognosis among patients with diabetes is not as promising as patients without diabetes. “I think it’s because we haven’t normalized the CVD risk,” he explained.

Promise of DPP-IV inhibition

The analysis included 18 trials of 4,998 patients randomly assigned to DPP-IV inhibitors and 3,546 to a comparative oral diabetes drug. A search of electronic databases identified trials published or unpublished in the literature until Sept. 30, 2011, that were at least 24 weeks.

Compared with placebo, the risk for adverse CV events was not significantly different with DPP-IV inhibitors (RR=1.05; 95% CI, 0.39-2.82); however, compared with metformin and other oral agents, including sulfonylureas and thiazolidinediones, the risk for CV events was significantly lower with DPP-IV inhibitor therapy (RR=0.42; 95% CI, 0.20-0.87 and RR=0.33; 95% CI, 0.16-0.67, respectively).

“It seems that DPP-IV inhibitors reduce cardiac events solely by lowering postprandial glucose; the same reductions have been shown with alfa-glucosidase inhibitors and quick-release bromocriptine-drugs which, by different mechanisms, only lower postprandial glucose. However, because DPP-IV is a ubiquitous enzyme involved in many other systems, it is possible that a non-metabolic action could explain the reduction in cardiac events. For example, DPP-IV inhibition increases the levels of HMGB1, a protein that increases angiogenesis and is deficient in patients with diabetes. Angiogenesis has been shown to be decreased in people with diabetes when compared with individuals without diabetes,” Bell told Endocrine Today.

Additionally, long-term use of DPP-IV inhibitors — specifically, trials at least 52 weeks — was associated with a lower risk for CV events compared with controls (RR=0.37; 95% CI, 0.21-0.63). However, this association was not observed in studies with less than 52 weeks of DPP-IV inhibitor treatment (RR=0.78; 95% CI, 0.38-1.60).

“This is all emerging data that needs to be confirmed, but both my clinical experience and work with these data make me pretty confident that we’re on the verge of a new era in treating diabetes that will be based on these incretin-based therapies,” O’Keefe said.