Cortisol is an essential hormone that helps regulate blood pressure and blood sugar, dampen inflammation, and control the sleep-wake cycle. In short bursts, cortisol is life-saving: a classic “fight-or-flight” response that mobilizes energy to escape danger. Think of a prehistoric ancestor facing a saber-toothed tiger. In that life-or-death moment, a surge of cortisol releases glucose into the bloodstream, spikes blood pressure, and primes the muscles to run or fight. For a brief encounter in the Ice Age, and still today in many real-life situations, this biological response is vital. But when persistently elevated, cortisol can be deadly.
New research suggests that excess cortisol (hypercortisolism) is more prevalent than once thought. Whether the source is job stress, life stress, or something more organic like a tumor in the adrenal gland, hypercortisolism keeps the body in a catabolic (breakdown) state, which can lead to osteoporosis (bone wasting), sarcopenia (muscle wasting), and chronically high blood glucose levels. For people already fighting T2D, that extra glucose is like adding fuel to the fire, making their diabetes very difficult to treat.
A Gap in Current Treatments
Modern T2D therapies—GLP-1 receptor agonists, SGLT2 inhibitors, and others—focus on lowering blood sugar. None directly address excess cortisol. As a result, patients with hypercortisolism may see little benefit from even the most effective regimens.
Clofutriben: A First-in-Class Solution
Sparrow’s lead candidate, clofutriben, is a first-in-class 11β-hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor that corrects and normalizes cortisol levels, giving other medicines a chance to work as intended. An upcoming Phase 2b trial (CAPTAIN-T2D) will randomize participants to clofutriben or placebo, measuring change in HbA1c after 24 weeks as the primary endpoint. A one percentage-point drop in A1c (representing a decrease in blood sugar of roughly 10% on average for a person with type 2 diabetes) would be considered a clinically significant success, as even a half-percentage-point drop in A1c is associated with reduced all-cause mortality and microvascular complications. The study will also explore whether participants can reduce or even discontinue other diabetes medications.
Rethinking Metabolic Dysfunction
One of the most intriguing possibilities is that some patients may not have classic diabetes at all. If their high blood sugar is driven primarily by elevated cortisol, normalizing cortisol could, in effect, eliminate their diabetes. It’s an ambitious goal, but one worth pursuing.
Next Steps
With Series B financing in place, Sparrow plans to launch CAPTAIN-T2D in early 2026, with data expected in 2027. If approved, clofutriben would represent the first new mechanism of action for type 2 diabetes in years and could open a promising new chapter in metabolic medicine.
At RiverVest, we believe innovation happens when science and strategy meet a genuine unmet need. By targeting the hidden role of cortisol, Sparrow is taking that kind of bold, science-driven step forward, and we are proud to support them in their pursuit.
