Effect of Pioglitazone on the Course of New-Onset Type 1 Diabetes Mellitus

Abstract

Objective: Type 1 diabetes mellitus (T1DM) is caused by insulin deficiency resulting from progressive destruction of β cells. The histological hallmark of the diabetic islet is mononuclear cell infiltration. Thiazolidinediones (TZDs) activate PPARg and enhance the actions of insulin. Studies in non-obese diabetic and streptocotozin-treated mouse models demonstrated that pretreatment with TZDs prevented the development of T1DM. The purpose of this study was to examine whether pioglitazone, given with insulin, preserved β cell function in patients with new-onset T1DM.Methods: This was a randomized, double-blind, placebo-controlled 24-week study. Subjects received pioglitazone or placebo. Blood sugar, glycated hemoglobin (HbA1c), C-peptide, and liver enzymes were measured at baseline. Boost© stimulated C-peptide responses were measured at baseline and at 24 weeks. Blood sugar, insulin dose, height, weight, and liver enzymes were monitored at each visit. HbA1c was performed every 12 weeks.Results: Of the 15 patients, 8 received pioglitazone, and 7 - placebo. There was no clinical improvement in HbA1c between or within groups at the completion of the study. Mean peak C-peptide values were similar between groups at baseline. Mean peak C-peptide level was slightly higher at 24 weeks in the pioglitazone group compared to the placebo (1.8 vs. 1.5ng/mL) which was considered as clinically insignificant. The interaction of HbA1c and insulin dose (HbA1c* insulin/kg/day), which combines degree of diabetic control and dose of insulin required to achieve this control, showed transient improvement in the pioglitazone group at 12 weeks but was not sustained at 24 weeks.Conclusion: In this pilot study, pioglitazone did not preserve β cell function when compared to placebo.Conflict of interest:None declared.

The efficacy and safety of SGLT2 inhibitors for adjunctive treatment of type 1 diabetes: a systematic review and meta-analysis

“…Alpha-glucosidase inhibitors provide a modest reduction in HbA1C and are associated with an increased risk of gastrointestinal reactions. The use of TZDs, however, pose a risk for development of AEs such as edema, weight gain, and possible worsening decline in endogenous insulin production 8 . Trials of GLP-1 analogs and DPP-4 inhibitors as insulin adjuncts in T1DM have also been conducted 9 10 , however, the effects remain to be seen.…”

“…In recent years, the use of adjunctive therapies to insulin—those that improve glucose metabolism and reduce insulin side effects—have become a popular topic of interest. A number of oral anti-diabetic agents have been tested in clinical trials as insulin adjuncts for management of T1DM, including thiazolidinediones (TZDs), biguanides, glucagon-like peptide 1 (GLP-1) analogs, alpha glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose co-transport-2 (SGLT-2) inhibitors 5 6 7 8 9 10 . Currently, pramlintide, a peptide hormone analog, is the only insulin adjunct that is approved by the U.S. Food and Drug Administration (FDA) for T1DM 11 .…”

The Time Is Right for a New Classification System for Diabetes: Rationale and Implications of the β-Cell–Centric Classification Schema

“…The principles of the β-cell–centric model provide a rationale for adjunctive therapy with noninsulin regimens in patients with type 1 DM (7,12–16). Thiazolidinedione (TZD) therapy in patients with type 1 DM presenting with IR, for example, is appropriate and can be beneficial (17).…”

Frequent Monitoring of C-Peptide Levels in Newly Diagnosed Type 1 Subjects Using Dried Blood Spots Collected at Home

“…There is increasing interest in interventions to preserve or even restore residual β -cell function in patients with T1D ( 9 ). Some drugs approved for treatment of type 2 diabetes have been investigated in pediatric T1D, such as thiazolidinediones ( 24 ) and glucagon-like peptide 1 receptor agonists ( 25 ), and a growing number of immunotherapy studies ( 26–31 ) are being conducted. Some T1D trials have reported some, if temporary, beneficial effects on β -cell function ( 26 , 27 , 29 , 31 ), although this effect led to reductions in insulin requirements in only a minority of patients ( 29 , 31 ).…”