Efficacy and safety of diazoxide for treating hyperinsulinemic hypoglycemia: A systematic review and meta-analysis

Abstract

Diazoxide is the first-line drug for treating hyperinsulinism and the only pharmacological agent approved for hyperinsulinism by the Federal Drug Administration. This systemic review and meta-analysis aimed to investigate the efficacy and safety of diazoxide for treating hyperinsulinemic hypoglycemia (HH). The meta-analysis of the efficacy and safety of diazoxide in treating HH was performed by searching relevant studies in the PubMed, Embase, and Cochrane databases. The findings were summarized, and the pooled effect size and its 95% confidence interval (CI) were calculated. A total of 6 cohort studies, involving 1142 participants, met the inclusion criteria. Among the cohort studies, the pooled estimate of the response rate of diazoxide therapy was 71% (95% CI 50%–93%, Pheterogeneity< 0.001, I2 = 98.3%, Peffect< 0.001). The common side effects were hypertrichosis (45%), fluid retention (20%), gastrointestinal reaction (13%), edema (11%), and neutropenia (9%). Other adverse events included pulmonary hypertension (2%) and thrombocytopenia (2%). This meta-analysis suggested that diazoxide was potentially useful in HH management; however, it had some side effects, which needed careful monitoring. Furthermore, well-designed large-scale studies, such as randomized controlled trials, might be necessary in the future to obtain more evidence.

Congenital hyperinsulinism in infancy and childhood: challenges, unmet needs and the perspective of patients and families

“…The first-line therapy for CHI is the adenosine triphosphate-sensitive potassium (K ATP ) channel activator diazoxide, the only therapy for CHI approved by the FDA and the EMA [ 37 , 38 ]. Diazoxide was also included in the Model List of Essential Medicines for Children in 2019 of the World Health Organization (WHO) for hypoglycemia [ 20 , 39 , 40 ]. The therapeutic dose range of diazoxide is relatively wide and can be adapted to the severity of disease [ 18 ].…”

Persistent hypoglycemia in the setting of metastatic malignant insulinoma to the liver treated with chemoembolization and bland embolization

“…Diazoxide therapy for control of hypoglycemia has had the greatest long-term benefit [7,8,9]. Some patients have gastrointestinal intolerance to the drug and in very high doses it may produce anorexia.…”

“…After the second discharge from the hospital, we used only Diazoxide which has been the only drug with excellent track record for long term treatment of hypoglycemia due to Insulinoma in the literature [7,8,9].…”

Pharmacological Modulation and (Patho)Physiological Roles of TRPM4 Channel—Part 1: Modulation of TRPM4

“…The most well-known action of diazoxide (IUPAC name: 7-chloro-3-methyl-4H-1lambda6,2,4-benzothiadiazine1,1-dioxide, Figure 1) is the activation of K ATP channels, enabling its use in the treatment of hypoglycemia [67]. As mentioned earlier, TRPM4 can form heteromer channels with SUR1, a subunit of K ATP channels [68].…”