Acute concomitant GIP receptor antagonism during GLP-1 receptor agonism does not affect appetite, resting energy expenditure or food intake in patients with type 2 diabetes and overweight/obesity
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Acute concomitant GIP receptor antagonism during GLP-1 receptor agonism does not affect appetite, resting energy expenditure or food intake in patients with type 2 diabetes and overweight/obesity. / Stensen, Signe; Krogh, Liva L.; Sparre-Ulrich, Alexander H.; Dela, Flemming; Hartmann, Bolette; Vilsbøll, Tina; Holst, Jens J; Rosenkilde, Mette M; Christensen, Mikkel B; Gasbjerg, Lærke S.; Knop, Filip K.
In: Diabetes, Obesity and Metabolism, Vol. 24, No. 9, 2022, p. 1882-1887.Research output: Contribution to journal › Journal article › peer-review
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T1 - Acute concomitant GIP receptor antagonism during GLP-1 receptor agonism does not affect appetite, resting energy expenditure or food intake in patients with type 2 diabetes and overweight/obesity
AU - Stensen, Signe
AU - Krogh, Liva L.
AU - Sparre-Ulrich, Alexander H.
AU - Dela, Flemming
AU - Hartmann, Bolette
AU - Vilsbøll, Tina
AU - Holst, Jens J
AU - Rosenkilde, Mette M
AU - Christensen, Mikkel B
AU - Gasbjerg, Lærke S.
AU - Knop, Filip K
N1 - This article is protected by copyright. All rights reserved.
PY - 2022
Y1 - 2022
N2 - AIMS: When combined with glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonism, antagonising the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) reduces body weight in rodent models of obesity. Here, we investigated the acute effects of GIPR antagonism combined with a GLP-1 infusion on determinants of body weight in patients with type 2 diabetes and overweight/obesity.MATERIALS AND METHODS: In a randomised, double-blind, placebo-controlled, crossover design, human synthetic GLP-1(7-36)NH 2 (0.75 pmol/kg/min) was infused together with the selective GIPR antagonist GIP(3-30)NH 2 (1,200 pmol/kg/min) or placebo for 320 minutes on two separate days covering an initial oral liquid mixed meal test and a terminal ad libitum meal. Appetite sensations, resting energy expenditure (REE) and food intake were evaluated, and subcutaneous adipose tissue (SAT) biopsies were analysed for triglyceride content. RESULTS: Ten patients with type 2 diabetes and overweight/obesity (mean±SD; HbA 1c 52±9 mmol/mol (7±1%); BMI 32.5±4.8 kg/m 2 ) were included. Compared to placebo, infusion of the GIPR antagonist GIP(3-30)NH 2 added to a GLP-1 infusion had no effect on appetite sensations, REE, food intake, or SAT triglyceride content during an ad libitum meal. Compared to placebo, GIP(3-30)NH 2 lowered plasma glucagon by -12.4±5.9% (p=0.037), and reduced serum insulin by -32.5±8.0% (p=0.027). CONCLUSIONS: During short term infusion, we found no effect of GIPR antagonism added to GLP-1R agonism on appetite sensations, REE, SAT triglyceride content or food intake in patients with type 2 diabetes and overweight/obesity. This article is protected by copyright. All rights reserved.
AB - AIMS: When combined with glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonism, antagonising the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) reduces body weight in rodent models of obesity. Here, we investigated the acute effects of GIPR antagonism combined with a GLP-1 infusion on determinants of body weight in patients with type 2 diabetes and overweight/obesity.MATERIALS AND METHODS: In a randomised, double-blind, placebo-controlled, crossover design, human synthetic GLP-1(7-36)NH 2 (0.75 pmol/kg/min) was infused together with the selective GIPR antagonist GIP(3-30)NH 2 (1,200 pmol/kg/min) or placebo for 320 minutes on two separate days covering an initial oral liquid mixed meal test and a terminal ad libitum meal. Appetite sensations, resting energy expenditure (REE) and food intake were evaluated, and subcutaneous adipose tissue (SAT) biopsies were analysed for triglyceride content. RESULTS: Ten patients with type 2 diabetes and overweight/obesity (mean±SD; HbA 1c 52±9 mmol/mol (7±1%); BMI 32.5±4.8 kg/m 2 ) were included. Compared to placebo, infusion of the GIPR antagonist GIP(3-30)NH 2 added to a GLP-1 infusion had no effect on appetite sensations, REE, food intake, or SAT triglyceride content during an ad libitum meal. Compared to placebo, GIP(3-30)NH 2 lowered plasma glucagon by -12.4±5.9% (p=0.037), and reduced serum insulin by -32.5±8.0% (p=0.027). CONCLUSIONS: During short term infusion, we found no effect of GIPR antagonism added to GLP-1R agonism on appetite sensations, REE, SAT triglyceride content or food intake in patients with type 2 diabetes and overweight/obesity. This article is protected by copyright. All rights reserved.
U2 - 10.1111/dom.14736
DO - 10.1111/dom.14736
M3 - Journal article
C2 - 35491518
VL - 24
SP - 1882
EP - 1887
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
SN - 1462-8902
IS - 9
ER -
ID: 311121885