Dual glucagon‐like peptide ‐1 and glucagon receptor agonism reduces energy intake in type 2 diabetes with obesity

Apr 2, 2024Diabetes, obesity & metabolism

Activating both GLP-1 and glucagon receptors reduces food intake in people with type 2 diabetes and obesity

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Abstract

The mean weight change for participants using cotadutide was -4.0% compared to -1.4% for those on placebo.

A total of 12 participants in the cotadutide group completed the study, compared to 7 in the placebo group.
Energy intake was significantly lower in the cotadutide group, with a reduction of -41.3% compared to placebo.
Energy expenditure showed minimal change between cotadutide and placebo groups, with a difference of 1.0% assessed by one method.
A more significant decrease in energy expenditure of -6.5% was observed with another method, but it was not the primary driver of weight loss.
The findings suggest that weight loss with cotadutide is mainly associated with decreased energy intake rather than changes in energy expenditure.

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AIMS: To establish which components of energy balance mediate the clinically significant weight loss demonstrated with use of cotadutide, a glucagon-like peptide-1 (GLP-1)/glucagon receptor dual agonist, in early-phase studies.

MATERIALS AND METHODS: We conducted a phase 2a, single-centre, randomized, placebo-controlled trial in overweight and obese adults with type 2 diabetes. Following a 16-day single-blind placebo run-in, participants were randomized 2:1 to double-blind 42-day subcutaneous treatment with cotadutide (100-300 μg daily) or placebo. The primary outcome was percentage weight change. Secondary outcomes included change in energy intake (EI) and energy expenditure (EE).

RESULTS: A total of 12 participants (63%) in the cotadutide group and seven (78%) in the placebo group completed the study. The mean (90% confidence interval [CI]) weight change was -4.0% (-4.9%, -3.1%) and -1.4% (-2.7%, -0.1%) for the cotadutide and placebo groups, respectively (p = 0.011). EI was lower with cotadutide versus placebo (-41.3% [-66.7, -15.9]; p = 0.011). Difference in EE (per kJ/kg lean body mass) for cotadutide versus placebo was 1.0% (90% CI -8.4, 10.4; p = 0.784), assessed by doubly labelled water, and -6.5% (90% CI -9.3, -3.7; p < 0.001), assessed by indirect calorimetry.

CONCLUSION: Weight loss with cotadutide is primarily driven by reduced EI, with relatively small compensatory changes in EE.

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Dual glucagon‐like peptide ‐1 and glucagon receptor agonism reduces energy intake in type 2 diabetes with obesity

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