Inhibition of dipeptidyl peptidase IV activity by oral metformin in Type 2 diabetes

JR Lindsay, NA Duffy, Aine McKillop, J Ardill, Finbarr O'Harte, Peter Flatt, PM Bell

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Aims Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) are important insulinotropic hormones that enhance the insulin secretory response to feeding. Their potential for treating Type 2 diabetes is limited by short biological half-life owing to degradation by dipeptidyl peptidase IV (DPP IV). We investigated the acute effects of metformin on DPP IV activity in Type 2 diabetes to elucidate inhibition of DPP IV as a possible mechanism of action. Methods Eight fasting subjects with Type 2 diabetes (5M/3F, age 53.1 +/- 4.2 years, BMI 36.8 +/- 1.8 kg/m(2), glucose 8.9 +/- 1.2 mmol/l, HbA(1c) 7.8 +/- 0.6%) received placebo or metformin 1 g orally 1 week apart in a random, crossover design. Results Following metformin, DPP IV activity was suppressed compared with placebo (AUC(0-6 h) 3230 +/- 373 vs. 5764 +/- 504 nmol ml/l, respectively, P = 0.001). Circulating glucose, insulin and total GLP-1 were unchanged. Metformin also concentration-dependently inhibited endogenous DPP IV activity in vitro in plasma from Type 2 diabetic subjects. Conclusion Oral metformin effectively inhibits DPP IV activity in Type 2 diabetic patients, suggesting that the drug may have potential for future combination therapy with incretin hormones.
LanguageEnglish
Pages654-657
JournalDiabetic medicine
Volume22
Issue number5
Publication statusPublished - May 2005

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Dipeptidyl Peptidase 4
Metformin
Type 2 Diabetes Mellitus
Glucagon-Like Peptide 1
Placebos
Gastric Inhibitory Polypeptide
Hormones
Insulin
Incretins
Glucose
Cross-Over Studies
Area Under Curve
Half-Life
Inhibition (Psychology)
Fasting
Pharmaceutical Preparations

Cite this

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title = "Inhibition of dipeptidyl peptidase IV activity by oral metformin in Type 2 diabetes",
abstract = "Aims Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) are important insulinotropic hormones that enhance the insulin secretory response to feeding. Their potential for treating Type 2 diabetes is limited by short biological half-life owing to degradation by dipeptidyl peptidase IV (DPP IV). We investigated the acute effects of metformin on DPP IV activity in Type 2 diabetes to elucidate inhibition of DPP IV as a possible mechanism of action. Methods Eight fasting subjects with Type 2 diabetes (5M/3F, age 53.1 +/- 4.2 years, BMI 36.8 +/- 1.8 kg/m(2), glucose 8.9 +/- 1.2 mmol/l, HbA(1c) 7.8 +/- 0.6{\%}) received placebo or metformin 1 g orally 1 week apart in a random, crossover design. Results Following metformin, DPP IV activity was suppressed compared with placebo (AUC(0-6 h) 3230 +/- 373 vs. 5764 +/- 504 nmol ml/l, respectively, P = 0.001). Circulating glucose, insulin and total GLP-1 were unchanged. Metformin also concentration-dependently inhibited endogenous DPP IV activity in vitro in plasma from Type 2 diabetic subjects. Conclusion Oral metformin effectively inhibits DPP IV activity in Type 2 diabetic patients, suggesting that the drug may have potential for future combination therapy with incretin hormones.",
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Inhibition of dipeptidyl peptidase IV activity by oral metformin in Type 2 diabetes. / Lindsay, JR; Duffy, NA; McKillop, Aine; Ardill, J; O'Harte, Finbarr; Flatt, Peter; Bell, PM.

In: Diabetic medicine, Vol. 22, No. 5, 05.2005, p. 654-657.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Inhibition of dipeptidyl peptidase IV activity by oral metformin in Type 2 diabetes

AU - Lindsay, JR

AU - Duffy, NA

AU - McKillop, Aine

AU - Ardill, J

AU - O'Harte, Finbarr

AU - Flatt, Peter

AU - Bell, PM

PY - 2005/5

Y1 - 2005/5

N2 - Aims Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) are important insulinotropic hormones that enhance the insulin secretory response to feeding. Their potential for treating Type 2 diabetes is limited by short biological half-life owing to degradation by dipeptidyl peptidase IV (DPP IV). We investigated the acute effects of metformin on DPP IV activity in Type 2 diabetes to elucidate inhibition of DPP IV as a possible mechanism of action. Methods Eight fasting subjects with Type 2 diabetes (5M/3F, age 53.1 +/- 4.2 years, BMI 36.8 +/- 1.8 kg/m(2), glucose 8.9 +/- 1.2 mmol/l, HbA(1c) 7.8 +/- 0.6%) received placebo or metformin 1 g orally 1 week apart in a random, crossover design. Results Following metformin, DPP IV activity was suppressed compared with placebo (AUC(0-6 h) 3230 +/- 373 vs. 5764 +/- 504 nmol ml/l, respectively, P = 0.001). Circulating glucose, insulin and total GLP-1 were unchanged. Metformin also concentration-dependently inhibited endogenous DPP IV activity in vitro in plasma from Type 2 diabetic subjects. Conclusion Oral metformin effectively inhibits DPP IV activity in Type 2 diabetic patients, suggesting that the drug may have potential for future combination therapy with incretin hormones.

AB - Aims Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) are important insulinotropic hormones that enhance the insulin secretory response to feeding. Their potential for treating Type 2 diabetes is limited by short biological half-life owing to degradation by dipeptidyl peptidase IV (DPP IV). We investigated the acute effects of metformin on DPP IV activity in Type 2 diabetes to elucidate inhibition of DPP IV as a possible mechanism of action. Methods Eight fasting subjects with Type 2 diabetes (5M/3F, age 53.1 +/- 4.2 years, BMI 36.8 +/- 1.8 kg/m(2), glucose 8.9 +/- 1.2 mmol/l, HbA(1c) 7.8 +/- 0.6%) received placebo or metformin 1 g orally 1 week apart in a random, crossover design. Results Following metformin, DPP IV activity was suppressed compared with placebo (AUC(0-6 h) 3230 +/- 373 vs. 5764 +/- 504 nmol ml/l, respectively, P = 0.001). Circulating glucose, insulin and total GLP-1 were unchanged. Metformin also concentration-dependently inhibited endogenous DPP IV activity in vitro in plasma from Type 2 diabetic subjects. Conclusion Oral metformin effectively inhibits DPP IV activity in Type 2 diabetic patients, suggesting that the drug may have potential for future combination therapy with incretin hormones.

M3 - Article

VL - 22

SP - 654

EP - 657

JO - Diabetes Medicine

T2 - Diabetes Medicine

JF - Diabetes Medicine

SN - 0742-3071

IS - 5

ER -