Takuya Haraguchi

<jats:sec> <jats:title/> <jats:p>Evaluation of insulin secretory capacity is essential to understand the pathophysiologic condition of individuals with diabetes and assess the efficacy of drugs used in the treatment of this disease. The 1-mg i.v. glucagon stimulation test (GST) is widely used to evaluate residual β-cell function; we previously reported that GST assessment of insulin secretory capacity is useful in assessing the efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs). However, recent reports have indicated that pharmacologic concentrations of glucagon stimulate insulin secretion through GLP-1 receptors, confounding the issue. The current studies were undertaken to reassess the reliability of the GST for evaluation of insulin secretory capacity under GLP-1RAs and dipeptidyl peptidase 4 inhibitors (DPP-4is). Our first study included individuals receiving GLP-1RA treatment, evaluated by the GST before and after treatment. Although the fasting C-peptide response (CPR) levels were elevated after treatment, the induction of insulin secretion by glucagon was significantly reduced. Our second study compared glucagon-induced insulin secretion between DPP-4i users and nonusers, assessed by the GST after propensity score matching. Although the fasting CPR levels were similar in the two investigations, glucagon-induced insulin secretion was significantly lower with DPP-4i use. These results suggest that the GST might underestimate insulin secretory capacity under incretin-based therapy.</jats:p> </jats:sec> <jats:sec> <jats:title>Article Highlights</jats:title> </jats:sec>

<h4>Context</h4>Roxadustat, a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, a recently developed class of drugs for treatment of anemia in chronic kidney disease (CKD), is reported to have a structure unlike that of other HIF-PH inhibitors but similar to that of triiodothyronine and bind to the thyroid hormone receptor in vitro. However, reports on the effects of roxadustat on thyroid function are limited and not detailed, and it remains unknown whether other HIF-PH inhibitors also affect thyroid function.<h4>Objective</h4>To compare the effect of roxadustat with daprodustat, another HIF-PH inhibitor, on thyroid function in patients with renal anemia in CKD.<h4>Methods</h4>This retrospective observational study included a total of 26 patients with anemia in CKD who were treated with roxadustat or daprodustat; thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were measured before and after treatment with the drugs.<h4>Results</h4>After initiation of roxadustat, TSH showed a significant decrease (2.4732 [1.7858-4.9016] μIU/mL before treatment and 0.659 [0.112-2.005] μIU/mL after treatment, P < .05); FT4 showed a significant decrease (0.93 [0.84-1.05] ng/dL before treatment and 0.70 [0.53-0.85] ng/dL after treatment, P < .01). After daprodustat initiation, neither TSH nor FT4 showed a significant change (TSH: 3.044 [1.853-4.171] μIU/mL before treatment and 2.893 [1.866-4.894] μIU/mL after treatment, P = .635; FT4 was 0.93 [0.81-1.00] ng/dL before treatment and 0.97 [0.87-1.05] ng/dL after treatment, P = .328).<h4>Conclusion</h4>Roxadustat decreases TSH and FT4 levels while daprodustat does not.