DPP-4 inhibitors may reduce risk of peripheral arterial disease, limb amputation
Treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors is associated with lower risk of peripheral arterial disease occurrence and limb amputation in patients with type 2 diabetes mellitus (T2D), according to a large-scale nationwide population-based cohort study.
“DPP-4 inhibitors are oral antihyperglycaemic agents that inhibit the breakdown of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, resulting in augmented glucose-dependent insulin secretion and suppression of glucagon production,” researchers said. [Diabetes Care 2007;30:1335–1343]
There were 3,369 DPP-4 inhibitor users and 3,880 DPP-4 inhibitor nonusers diagnosed with peripheral arterial disease during the mean follow-up of 3.0 years (maximum 4.8 years). DPP-4 inhibitor users had a lower risk of peripheral arterial disease (hazard ratio [HR], 0.84; 95 percent CI, 0.80 to 0.88) than nonusers. [Am J Med 2017;130:348–355]
Users of DPP-4 inhibitor also had a reduced rate of lower-extremity amputation compared with nonusers (HR, 0.65; 0.54 to 0.79). In addition, subgroup analysis showed a consistent association between the use of DPP-4 inhibitors and risk of peripheral arterial disease.
“We demonstrated that DPP-4 inhibitor users have a 16-percent decrease in the risk of developing peripheral arterial disease compared with DPP-4 inhibitor nonusers,” researchers said. “Of particular note is that DPP-4 inhibitor users had significantly reduced risk of lower-extremity amputation.”
A retrospective registry analyses using Taiwan’s National Health Insurance Research Database was conducted to examine the association between the use of DPP-4 inhibitors and risk of peripheral arterial disease in patients with T2D. A total of 82,169 propensity score-matched participants (mean age 58.9 years; 54 percent male) were evaluated for the period 2009 to 2011.
“Our study also provided additional clinical evidence about the vascular protective effects of DPP-4 inhibitors,” researchers said. “However, we observed that the vascular protective effect of DPP-4 inhibitors was significant only in patients using metformin concomitantly in subgroup analysis.”
This study, however, has several limitations. These include unmeasured confounding due to the use of administrative data, lack of information on indices of blood sugar control, and the exclusion of personal information (such as body mass index, dietary habits, physical activity, smoking status), clinical laboratory data, or detailed images.
Despite these limitations, researchers argued that their findings may provide pivotal clinical and therapeutic implications. However, further prospective clinical and experimental studies are needed to verify such findings and clarify the mechanisms responsible for producing these beneficial effects.
Patients with diabetes are at an extremely high risk of developing peripheral arterial disease, which is characterized by symptoms of intermittent claudication or critical limb ischemia. Peripheral arterial disease is a major risk factor for lower-extremity amputation and is also accompanied by a heightened risk of cardiovascular and cerebrovascular diseases. [Vasc Med 2001;6:3–7; Vasc Med 1997;2:221–226]