Summary: In a crossover study in healthy trained adults, a whey-protein-only drink raised GLP-1 (more and longer) and amino acids and lowered glucose, while a carbohydrate-only drink produced a larger insulin and GIP response; protein also increased 24-hour urinary nitrogen excretion.
PICO Summary
| Element | Detail |
|---|---|
| Population | 14 young, healthy, moderate-to-well-trained adults; double-blind randomised crossover, Norway. |
| Intervention | Isoenergetic whey-protein-only drink (1.2 g/kg). |
| Comparison | Isoenergetic carbohydrate-only drink, on separate days. |
| Outcome | Protein lowered glucose and raised amino acids; carbohydrate raised glucose. Insulin rose with both but more with carbohydrate. GLP-1 rose more with protein and stayed elevated past 240 minutes; GIP rose more with carbohydrate. Protein increased 24-hour urinary nitrogen, mainly 2–8 hours after intake. |
Expert Commentary
This is a clean physiology study that nicely illustrates why macronutrient choice, not just calorie count, shapes the hormonal response to a meal. The standout finding is the divergence in incretins: protein preferentially and durably stimulated GLP-1, the very pathway our most effective obesity and diabetes drugs exploit, while carbohydrate drove GIP and a sharper insulin spike. That gives a tidy mechanistic basis for the well-known satiating effect of protein and for the food-order trick of eating protein before carbohydrate. The trade-off is also instructive: the rise in urinary nitrogen quantifies the renal work of processing protein, a reminder that high intakes are not free in patients with kidney disease. The honest caveat is generalisability, this was 14 healthy, fit young adults given single-macronutrient drinks, which is a long way from a person with diabetes eating a mixed meal. Can I use this with my patients? Yes, as supportive rationale for advice I already give, favouring adequate protein at meals for satiety and steadier glucose, and considering protein-first sequencing, while individualising protein targets according to renal function rather than pushing high intake indiscriminately.
References
Clauss M, Puissant C, Bastani NE, et al. Effect of high intakes of protein-only and carbohydrate-only on plasma metabolites and hormones, in addition to nitrogen excretion. Front Endocrinol (Lausanne). 2025;16:1618142. doi:10.3389/fendo.2025.1618142