GIP Infusion Has No Clear Benefits for Patients Treated With GLP-1 Receptor Agonists

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Treatment with intravenous glucose-dependent insulinotropic polypeptide had no acute beneficial effects on appetite, energy intake, or energy expenditure in type 2 diabetes.

In patients with type 2 diabetes treated with glucagon-like peptide 1 (GLP-1) receptor agonists, additional treatment with intravenous glucose-dependent insulinotropic polypeptide (GIP) had no acute beneficial effects on appetite, energy intake, or energy expenditure, according to study results published in Diabetes Care.

While in healthy people GLP-1 and GIP have additive insulinotropic effects and account for a significant amount of the total insulin secreted after an oral glucose tolerance test, studies in patients with type 2 diabetes have found that co-administration of these hormones does not induce an additional glucose-lowering effect compared with GLP-1 administration alone.

The goal of the current study was to explore the effects of high-dose GIP infusion on energy intake in patients with type 2 diabetes, which was the primary end point. Effects on energy expenditure, glucose concentration, lipid profile, glucose-regulating hormones, gastric emptying, and gallbladder motility were also evaluated.

The randomized double-blind study ( Identifier: NCT03526289) included 22 men with type 2 diabetes (mean hemoglobin A1c, 6.8%) treated with metformin and long-acting GLP-1 receptor agonists. Each patient underwent 2 experimental days: 1 day of 5-hour GIP infusion (6 pmol/kg/min) and 1 day of 5-hour placebo infusion. After 1 hour, the participants ingested a standardized liquid mixed meal for evaluation of gastric emptying. At 3 hours postinfusion, an ad libitum meal of pasta Bolognese was served and weighted before and after the meal to assess energy intake. The order of the experimental days was randomized, with a washout period of ≥72 hours.

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With regard to the primary end point, energy intake from the ad libitum meal was similar with infusion of GIP or placebo (648±74 vs 594±55 kcal, respectively; P =.480). Water intake was also similar during GIP vs placebo infusion.

Energy expenditure did not differ between the interventions at any measured time point. Hunger, satiety, fullness, food consumption, and thirst were statistically similar in both study days, as were lipid profiles, gallbladder volumes, and gastric emptying.

Plasma glucagon levels were higher during GIP infusion compared with placebo infusion (area under the curve: 4357±430 vs 3655±377 pmol/L × min, respectively; P =.026), as were glucose levels (area under the curve: 2394±74 vs 2260±62 mmol/L × min, respectively; P =.017).

The researchers noted that they could not exclude that a clinically relevant increase in energy intake with GIP infusion might have been overlooked due to lack of power.

“These findings do not indicate acute metabolic benefits of GIP administration on top of stable GLP-1 [receptor] agonism in men with type 2 diabetes,” concluded the researchers.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Bergmann NC, Gasbjerg LS, Heimbürger SM, et al. No acute effects of exogenous glucose-dependent insulinotropic polypeptide on energy intake, appetite, or energy expenditure when added to treatment with a long-acting glucagon-like peptide 1 receptor agonist in men with type 2 diabetes [published online January 16, 2020]. Diabetes Care. doi:10.2337/dc19-0578