In the Journals

Switching DPP-IV inhibitor in type 2 diabetes may reduce albuminuria

Adults with type 2 diabetes who switched from other DPP-IV inhibitors to teneligliptin for 24 weeks had decreased plasma DPP-IV activity, which was associated with a reduction in albuminuria, but they had no change in glucose levels, according to data from a single-arm, open-label, observational study published in the Journal of Diabetes Investigation.

“Multiple DPP-4 inhibitors are available in the current clinical setting,” Daisuke Koya, MD, PhD, professor in the department of diabetology and endocrinology at Kanazawa Medical University in Japan, and colleagues wrote. “DPP-4 inhibitors may show differences in DPP-4 inhibitory action on glucose control and reno-protection. However, the differences in the reno-protective effect for diabetic kidney disease among DPP-4 inhibitors are unclear. In this study, our data clearly indicated that teneligliptin may have stronger inhibitory action against DPP-4 than other DPP-4 inhibitors because the plasma DPP-4 activity was significantly decreased after switching to teneligliptin.”

The researchers evaluated 23 outpatients with type 2 diabetes who visited the department of endocrinology and metabolism at their institution. At baseline, patients had HbA1c levels of 6% or greater and urinary albumin to creatinine ratio (UACR) of 30 mg/gCr or greater in spot urine during screening for diabetic kidney disease. All participants had been receiving treatment with another DPP-IV inhibitor, including linagliptin (Tradjenta, Boehringer Ingelheim), sitagliptin (Januvia, Merck), vildagliptin, anagliptin or alogliptin (Nesina, Takeda), as well as other antidiabetes agents. Seven participants received insulin, and all participants received renin-angiotensin system inhibitors. Three patients received spironolactone. Patients were switched from their current DPP-IV inhibitor to 20 mg per day of teneligliptin.

After patients switched to teneligliptin, researchers found no significant differences in HbA1c levels, fasting plasma glucose levels, UACR, renal and liver function tests, lipid data, BMI or blood pressure. Plasma DPP-IV activity showed a tendency to decrease from baseline at 8 weeks after switching (from 1.49 nmol/min/mL to 0.78 nmol/min/mL; P = .139). After 24 weeks, plasma DPP-IV decreased to 0.57 nmol/min/mL (P = .012). Researchers observed a positive correlation between the change rate of plasma DPP-IV activity for 24 weeks and both plasma DPP-IV activity (r = –0.5997; P = .0025) and FPG levels (r = –0.4235; P = .044) at baseline, but there was no correlation between plasma DPP-IV activity at baseline and FPG levels at baseline. Data also showed a positive correlation between the change rate of plasma DPP-IV and the change rate of the UACR (r = 0.556; P = .0059).

Change amounts in HbA1c, FPG, UACR, BMI and BP were not correlated with the change rate of plasma DPP-IV at 24 weeks after switching. Researchers did not observe significant correlations between change rate of the UACR and plasma DPP-IV activity at baseline, change rate of UACR and FPG at baseline, change rate of plasma DPP-IV and amount of HbA1c change or the amount of HbA1c change and change rate of the UACR. They concluded that the change rate of plasma DPP-IV after teneligliptin treatment contributed to the change rate of the UACR independent of the change in glucose control, BMI or BP at 24 weeks and plasma DPP-IV activity and FPG at baseline.

“The detailed mechanism by which teneligliptin decreases the UACR through a reduction in DPP-4 activity in a glucose-lowering-independent manner is unclear; therefore, further study is necessary to elucidate these points,” the researchers wrote. – by Tina DiMarcantonio-Brown

Disclosures: The authors report their work was financially supported by Mitsubishi Tanabe Pharma.

Adults with type 2 diabetes who switched from other DPP-IV inhibitors to teneligliptin for 24 weeks had decreased plasma DPP-IV activity, which was associated with a reduction in albuminuria, but they had no change in glucose levels, according to data from a single-arm, open-label, observational study published in the Journal of Diabetes Investigation.

“Multiple DPP-4 inhibitors are available in the current clinical setting,” Daisuke Koya, MD, PhD, professor in the department of diabetology and endocrinology at Kanazawa Medical University in Japan, and colleagues wrote. “DPP-4 inhibitors may show differences in DPP-4 inhibitory action on glucose control and reno-protection. However, the differences in the reno-protective effect for diabetic kidney disease among DPP-4 inhibitors are unclear. In this study, our data clearly indicated that teneligliptin may have stronger inhibitory action against DPP-4 than other DPP-4 inhibitors because the plasma DPP-4 activity was significantly decreased after switching to teneligliptin.”

The researchers evaluated 23 outpatients with type 2 diabetes who visited the department of endocrinology and metabolism at their institution. At baseline, patients had HbA1c levels of 6% or greater and urinary albumin to creatinine ratio (UACR) of 30 mg/gCr or greater in spot urine during screening for diabetic kidney disease. All participants had been receiving treatment with another DPP-IV inhibitor, including linagliptin (Tradjenta, Boehringer Ingelheim), sitagliptin (Januvia, Merck), vildagliptin, anagliptin or alogliptin (Nesina, Takeda), as well as other antidiabetes agents. Seven participants received insulin, and all participants received renin-angiotensin system inhibitors. Three patients received spironolactone. Patients were switched from their current DPP-IV inhibitor to 20 mg per day of teneligliptin.

After patients switched to teneligliptin, researchers found no significant differences in HbA1c levels, fasting plasma glucose levels, UACR, renal and liver function tests, lipid data, BMI or blood pressure. Plasma DPP-IV activity showed a tendency to decrease from baseline at 8 weeks after switching (from 1.49 nmol/min/mL to 0.78 nmol/min/mL; P = .139). After 24 weeks, plasma DPP-IV decreased to 0.57 nmol/min/mL (P = .012). Researchers observed a positive correlation between the change rate of plasma DPP-IV activity for 24 weeks and both plasma DPP-IV activity (r = –0.5997; P = .0025) and FPG levels (r = –0.4235; P = .044) at baseline, but there was no correlation between plasma DPP-IV activity at baseline and FPG levels at baseline. Data also showed a positive correlation between the change rate of plasma DPP-IV and the change rate of the UACR (r = 0.556; P = .0059).

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Change amounts in HbA1c, FPG, UACR, BMI and BP were not correlated with the change rate of plasma DPP-IV at 24 weeks after switching. Researchers did not observe significant correlations between change rate of the UACR and plasma DPP-IV activity at baseline, change rate of UACR and FPG at baseline, change rate of plasma DPP-IV and amount of HbA1c change or the amount of HbA1c change and change rate of the UACR. They concluded that the change rate of plasma DPP-IV after teneligliptin treatment contributed to the change rate of the UACR independent of the change in glucose control, BMI or BP at 24 weeks and plasma DPP-IV activity and FPG at baseline.

“The detailed mechanism by which teneligliptin decreases the UACR through a reduction in DPP-4 activity in a glucose-lowering-independent manner is unclear; therefore, further study is necessary to elucidate these points,” the researchers wrote. – by Tina DiMarcantonio-Brown

Disclosures: The authors report their work was financially supported by Mitsubishi Tanabe Pharma.