In the Journals

DPP-IV inhibitor shows little effect on adipose tissue inflammation

The DPP-IV inhibitor saxagliptin has a minimal effect on adipose tissue inflammation, arteriole vasodilation and postprandial endothelial function in adults with overweight or obesity, according to findings published in Diabetic Medicine.

“The DPP-IV inhibitors are a relatively new class of type 2 diabetes medications. Recent evidence suggests additional metabolic and vascular benefits of DPP-IV inhibitors, including amelioration of dyslipidemia and endothelial dysfunction,” Juraj Koska, MD, PhD, a research health scientist and principal investigator at Carl T. Hayden Medical Research Foundation in the Phoenix VA Health Care System, and colleagues wrote. “In humans, DPP-IV inhibitors decreased multiple blood proinflammatory markers in those with type 2 diabetes and inhibited both systemic and adipose tissue inflammation in HIV-positive people with impaired glucose tolerance.”

Koska and colleagues conducted a randomized, double-blind, placebo-controlled study with 44 participants from the Phoenix VA Health Care System between June 2013 and November 2016. All participants were U.S. veterans aged 21 to 70 years and had a BMI between 27.5 kg/m2 and 37.5 kg/m2. The researchers excluded participants with diabetes “to limit confounding of the analysis of adipose tissue inflammation by the glucose-lowering effect of saxagliptin.”

Baseline measurements were taken for endothelial function and plasma concentrations of lipids, glucose and insulin. Endothelial function was measured via plasma glucose, insulin and triglyceride levels and peripheral arterial tonometry at 2 and 4 hours after a 400-kcal/m2 high-fat breakfast. Participants also underwent biopsies of 5-g to 7-g abdominal subcutaneous fat tissue.

After baseline measurement, participants were randomly assigned at a 2:1 ratio to saxagliptin (Onglyza, AstraZeneca) or placebo. Participants in the saxagliptin group (n = 28; mean age, 55 years; 11% women; mean BMI, 31.8 kg/m2) took one tablet orally each day while maintaining routines in exercise and diet. The placebo group (n = 16; mean age, 58 years; 12% women; mean BMI, 34.7 kg/m2) was also instructed to make no diet or exercise changes.

After 6 weeks, the researchers found increases in the 6- and 24-hour interleukin-8 measurements in adipose tissue in the placebo group (median fold-change from baseline of 2 in saxagliptin and 3.3 in placebo; P = .03 and P = .006, respectively).

“Although indicative of a protective effect of saxagliptin against adipose tissue inflammation, this observation should be interpreted with caution as it is difficult to explain why these inflammatory markers would increase over 6 weeks in the placebo group,” the researchers wrote.

Saxagliptin lowered thioredoxin-inhibitory protein levels (P = .02) and plasma glucose concentrations after the high-fat breakfast (P = .02).

Conversely, there were no significant changes found between the two groups in the concentrations of IL-1b, IL-6, monocyte chemoattractant protein-1 at the 6- and 24-hour adipose tissue media. Saxagliptin was not associated with significant change in adipose tissue macrophage content or mRNA expression levels of inflammation-related genes, according to the researchers, and had little effect on insulin-induced vasodilation of adipose tissue arterioles.

“Although the participants in the present study were without type 2 diabetes, the lack of significant improvement in adipose tissue inflammation and vascular function is consistent with the generally neutral effect of saxagliptin and other DPP-IV inhibitors on cardiovascular events in recent cardiovascular outcome trials,” the researchers wrote. – by Phil Neuffer

Disclosures: This study was supported by a grant from AstraZeneca. Koska reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

The DPP-IV inhibitor saxagliptin has a minimal effect on adipose tissue inflammation, arteriole vasodilation and postprandial endothelial function in adults with overweight or obesity, according to findings published in Diabetic Medicine.

“The DPP-IV inhibitors are a relatively new class of type 2 diabetes medications. Recent evidence suggests additional metabolic and vascular benefits of DPP-IV inhibitors, including amelioration of dyslipidemia and endothelial dysfunction,” Juraj Koska, MD, PhD, a research health scientist and principal investigator at Carl T. Hayden Medical Research Foundation in the Phoenix VA Health Care System, and colleagues wrote. “In humans, DPP-IV inhibitors decreased multiple blood proinflammatory markers in those with type 2 diabetes and inhibited both systemic and adipose tissue inflammation in HIV-positive people with impaired glucose tolerance.”

Koska and colleagues conducted a randomized, double-blind, placebo-controlled study with 44 participants from the Phoenix VA Health Care System between June 2013 and November 2016. All participants were U.S. veterans aged 21 to 70 years and had a BMI between 27.5 kg/m2 and 37.5 kg/m2. The researchers excluded participants with diabetes “to limit confounding of the analysis of adipose tissue inflammation by the glucose-lowering effect of saxagliptin.”

Baseline measurements were taken for endothelial function and plasma concentrations of lipids, glucose and insulin. Endothelial function was measured via plasma glucose, insulin and triglyceride levels and peripheral arterial tonometry at 2 and 4 hours after a 400-kcal/m2 high-fat breakfast. Participants also underwent biopsies of 5-g to 7-g abdominal subcutaneous fat tissue.

After baseline measurement, participants were randomly assigned at a 2:1 ratio to saxagliptin (Onglyza, AstraZeneca) or placebo. Participants in the saxagliptin group (n = 28; mean age, 55 years; 11% women; mean BMI, 31.8 kg/m2) took one tablet orally each day while maintaining routines in exercise and diet. The placebo group (n = 16; mean age, 58 years; 12% women; mean BMI, 34.7 kg/m2) was also instructed to make no diet or exercise changes.

After 6 weeks, the researchers found increases in the 6- and 24-hour interleukin-8 measurements in adipose tissue in the placebo group (median fold-change from baseline of 2 in saxagliptin and 3.3 in placebo; P = .03 and P = .006, respectively).

“Although indicative of a protective effect of saxagliptin against adipose tissue inflammation, this observation should be interpreted with caution as it is difficult to explain why these inflammatory markers would increase over 6 weeks in the placebo group,” the researchers wrote.

Saxagliptin lowered thioredoxin-inhibitory protein levels (P = .02) and plasma glucose concentrations after the high-fat breakfast (P = .02).

Conversely, there were no significant changes found between the two groups in the concentrations of IL-1b, IL-6, monocyte chemoattractant protein-1 at the 6- and 24-hour adipose tissue media. Saxagliptin was not associated with significant change in adipose tissue macrophage content or mRNA expression levels of inflammation-related genes, according to the researchers, and had little effect on insulin-induced vasodilation of adipose tissue arterioles.

“Although the participants in the present study were without type 2 diabetes, the lack of significant improvement in adipose tissue inflammation and vascular function is consistent with the generally neutral effect of saxagliptin and other DPP-IV inhibitors on cardiovascular events in recent cardiovascular outcome trials,” the researchers wrote. – by Phil Neuffer

Disclosures: This study was supported by a grant from AstraZeneca. Koska reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.