Cyproheptadine = Diabetes/Insulin Resistance. Myth?

[Lokzo]

Hey everyone,

Why is everyone so concerned about Cyproheptadine worsening insulin resistance/diabetes risk?

Is this only relevant if someone was to use it DAILY, at doses above say 1mg?


Effect of cyproheptadine administration on insulin secretion in acromegalic, diabetic and normal subjects.
Effect of cyproheptadine administration on insulin secretion in acromegalic, diabetic and normal subjects. - PubMed - NCBI

Sci-Hub | The effects of cyproheptadine on glucose tolerance and pancreatic islets in rats. Acta Diabetologica Latina, 18(2), 107–114 | 10.1007/BF02098995
This study was using:
CPH hydrochloride (Sharp and Dohme, M/inchen, FRG), in aqueous solution,
was given orally by gastric intubation at a dose of 45 mg/kg body weight. Groups
of rats received 3, 5, 10, or 20 consecutive daily doses.


[Comparison of experimental diabetes induced by streptozotocin and cyproheptadine].
[Comparison of experimental diabetes induced by streptozotocin and cyproheptadine]. - PubMed - NCBI


Has anyone found anything else on Cyproheptadine affecting insulin/blood sugar?

 

[Kartoffel]

Large doses of cyproheptadine reversibly deplete pancreatic cells of insulin, in rats. It doesn't give them diabetes. The same doesn't seem to happen in humans, and the temporary hyperglycemia induced by cypro strongly protects rats' beta cells against toxins that normally induce irreversible diabetes (alloxan)

https://www.sciencedirect.com/science/article/pii/027205909190146U

"Pretreatment with an oral dose (45 mg/kg) of cyproheptadine (CPH), a drug that inhibits secretion and synthesis of insulin, 3 hr before alloxan (100 mg/kg, iv) protects mice from the permanent diabetes produced by alloxan. Pretreated animals at the time of alloxan administration were hyperglycemic. Therefore, the possibility that CPH-induced hyperglycemia protected mice from alloxan was investigated. This was accomplished by giving mannoheptulose (a glucose antagonist) or insulin (to lower blood glucose) after CPH and before alloxan. These interventions eliminated CPH-induced protection from alloxan, indicating a role for CPH-induced hyperglycemia in the protective effect. To confirm that CPH does not protect mice from alloxan-induced diabetes by a direct action, in vitro experiments using isolated pancreatic islets were conducted. Mouse islets were pretreated with CPH, its metabolite desmethylcyproheptadine (DMCPH), or an equal mixture of the two and/or various concentrations of glucose prior to an acute exposure to a toxic concentration of alloxan. Glucose-stimulated insulin release was used as a measure of pancreatic β-cell function after alloxan exposure. CPH or DMCPH (alone or in combination) pretreatment did not provide protection against alloxan-induced inhibition of insulin release nor did pretreatments potentiate the protective action of glucose against in vitro alloxan toxicity. The results indicate that the protective action of CPH when given to mice before alloxan is due to drug-induced hyperglycemia and not to a direct effect of CPH or its metabolite"