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Tirzepatide preserves the body’s key hormonal defenses against hypoglycemia in type 2 diabetes, maintaining normal glucagon responses even during controlled low-glucose conditions.
In type 2 diabetes (T2D), the body’s ability to mount a protective hormonal response during low blood sugar is frequently compromised. As tirzepatide (glucose-dependent insulinotropic polypeptide receptor/glucagon-like peptide-1 receptor [GIPR/GLP-1R] agonist) continues to rise in clinical use for its dual metabolic actions, interest has grown around how it interacts with these critical physiologic systems.
Researchers conducted a controlled investigation to see whether tirzepatide influenced glucagon dynamics or disrupted other hormonal components of the hypoglycemia defense mechanism.
The phase 1 trial followed a randomized, placebo-controlled crossover design in 42 adults with T2D. Participants received 15 mg tirzepatide or placebo for 12 weeks, completed an 8–10-week washout, and switched treatments. A hypoglycemic clamp reduced glucose from 100 to 45 mg/dL to evaluate glucagon and other counterregulatory hormones.
Researchers also tracked recovery time and hypoglycemic symptoms using validated scales, analyzing all measures under prespecified safety criteria. The results showed that:
In conclusion, the study showed that tirzepatide preserved the essential glucagon response to hypoglycemia while easing symptom burden.
Frontiers in Endocrinology
Counterregulatory response to hypoglycemia during a hypoglycemic clamp in people with type 2 diabetes treated with tirzepatide
Thomas R Pieber et al.
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