The ghrelin receptor agonist capromorelin initially reduced insulin secretion and worsened blood sugar control in healthy cats, but these metabolic effects largely normalized after 30 days of treatment.
72% drop in first-phase insulin responseCapromorelin dramatically blunted initial insulin secretion on day 1, though partial recovery occurred by day 30
What the researchers found
Capromorelin activates the ghrelin receptor (GHSR), which is found on pancreatic delta cells that produce somatostatin. Activating delta cells was expected to suppress insulin secretion.
On day 1:
- Fasting blood glucose increased by 13 mg/dL (p < 0.0001)
- Insulin decreased (p = 0.03)
- Glucagon was unchanged
- First-phase insulin response (FPIR) during glucose tolerance test dropped by 72% (from 17,437 to 4,931 ng/L/15min, p = 0.004)
Days 2-4:
- Mean interstitial glucose rose by 19 mg/dL (p = 0.03)
- Glycemic variability increased (SD 9.7 vs 5.0, p = 0.02)
By day 30:
- Glucose tolerance returned to baseline
- Glycemic variability normalized
- But FPIR was still partially blunted (9,993 vs 17,437, p = 0.045)
The body appeared to compensate for the initial insulin suppression over time.
Why it matters
This study has implications beyond veterinary medicine. Ghrelin receptor agonists like MK-677 (ibutamoren) are widely used in human growth hormone optimization. Understanding that ghrelin receptor activation temporarily impairs insulin secretion and glucose control is important for anyone considering these compounds, particularly people with existing insulin sensitivity concerns. The finding that metabolic effects normalize over 30 days suggests an adaptation mechanism worth understanding.
The numbers in context
Day 1: fasting glucose +13mg/dL; FPIR dropped 72%; Days 2-4: glucose +19mg/dL; Day 30: glucose tolerance normalized
How the study worked
Seven healthy cats received capromorelin daily for 30 days. Intravenous glucose tolerance tests were performed on days -3 (baseline), 1, and 30 to assess insulin secretion and glucose clearance. Continuous glucose monitoring tracked interstitial glucose levels and glycemic variability. Blood samples measured fasting glucose, insulin, and glucagon at multiple time points.
Who was studied
7 healthy cats (animal study)
What this study cannot tell us
Only 7 cats were studied, which is a very small sample size. Only healthy cats were tested — diabetic, obese, or insulin-resistant cats might respond differently or not adapt as well. The 30-day treatment period may not reveal longer-term metabolic consequences. The specific mechanism by which the body compensated for insulin suppression was not fully explored. Results from cats may not directly translate to other species.
How to read the evidence
This is a small animal study with only 7 cats. While the study design includes baseline controls and multiple time points, the very small sample size limits statistical power. The prospective design with continuous glucose monitoring adds strength, but these are preliminary findings that need replication in larger cohorts.
When this study was published
Published in 2021, this study remains relevant as ghrelin receptor agonists continue to be widely used in veterinary medicine and studied for human applications. No major subsequent studies have contradicted these metabolic findings.
The bigger picture
Ghrelin receptor agonists are of significant interest in both veterinary and human medicine — for appetite stimulation, growth hormone release, and metabolic regulation. This study reveals an important trade-off: activating the ghrelin receptor boosts appetite and growth hormone but temporarily suppresses insulin and raises blood sugar. This has direct relevance to human use of similar compounds like MK-677, where metabolic side effects are a well-known concern.
Questions still open
- Does the same metabolic adaptation occur in diabetic or pre-diabetic animals, or does the insulin suppression persist?
- Do human ghrelin receptor agonists like MK-677 produce similar temporary insulin suppression followed by metabolic normalization?
- What is the specific compensatory mechanism that restores glucose tolerance despite continued ghrelin receptor activation?
Common questions
Is capromorelin related to MK-677 (ibutamoren)?
Should I be concerned about blood sugar if my cat takes capromorelin?
Read the original research
The effect of the ghrelin-receptor agonist capromorelin on glucose metabolism in healthy cats.
Domestic animal endocrinology, 74, 106484
Citation
Pires, J; Greathouse, R L; Quach, N; Huising, M O; Crakes, K R; Miller, M; Gilor, C. (2021). The effect of the ghrelin-receptor agonist capromorelin on glucose metabolism in healthy cats.. Domestic animal endocrinology, 74, 106484. https://doi.org/10.1016/j.domaniend.2020.106484