Glucagon

Glucagon is the body's own counter-regulatory hormone to insulin, and its emergency-use drug formulations for severe hypoglycemia are real and FDA-approved — but the newer, easier-to-use ones are a genuinely interesting case of trading a slightly softer public evidence base for a much larger practical improvement. Baqsimi (2019, nasal powder) rests on a real published noninferiority trial. Gvoke (2019-2021, prefilled syringe/autoinjector) rested on trials that reached FDA mostly as unpublished data summarized in the package insert — real evidence for the regulator, but thinner in the independently checkable public literature than most drugs on this site.

What it is, and the older reconstituted kits

Glucagon is a 29-amino-acid pancreatic peptide hormone that raises blood glucose by triggering hepatic glycogen breakdown — the physiological opposite of insulin. For decades, the only approved emergency treatments for severe hypoglycemia were injectable glucagon kits requiring reconstitution: mixing a powder vial with a diluent syringe by hand, under real time pressure, often performed by a frightened bystander rather than a clinician — a well-recognized practical failure point in actual emergencies.

Baqsimi: the first non-injectable form

FDA approved Baqsimi (glucagon nasal powder, 3mg, Eli Lilly) on July 24, 2019, as the first non-injectable glucagon product, for ages 4 and up. A randomized crossover noninferiority trial in adults with type 1 diabetes (Rickels et al., Diabetes Care 2016;39:264-270, PMID 26681725) compared intranasal glucagon against injectable glucagon during insulin-induced hypoglycemia and found it noninferior on the glucose-recovery endpoint — a real, published, peer-reviewed trial.

Gvoke: ready-to-use liquid, thinner public trial record

FDA approved Gvoke (Xeris Pharmaceuticals) — a room-temperature-stable liquid glucagon formulation not requiring reconstitution — as a prefilled syringe and autoinjector on September 10, 2019, and as a simpler single-use vial-and-syringe kit in August 2021. Its pivotal trials were two unpublished, randomized crossover studies in 161 adults total, plus a single-arm study in 31 children, summarized in FDA review documents and conference abstracts rather than a standard peer-reviewed publication as best we could determine. Reported treatment-success rates were high in both groups — around 99% in adults, 100% in children.

What all of these are actually tested against

For ethical reasons, no modern glucagon rescue-product trial uses a placebo arm in real hypoglycemia — patients are randomized to the new formulation versus the older injectable standard, with success defined as raising blood glucose above a threshold within a set time window. That's a clinically sensible design, but it's worth being explicit that "glucagon products work" rests on this substitution logic (new form vs. old form, in engineered hypoglycemia) rather than large outcome trials measuring hospitalization or death avoided in real-world emergencies.