Feasibility of DPP-4 Inhibitor Therapy on Advanced Hybrid Closed Loop System

Feasibility of DPP-4 Inhibitor for the Treatment of Iftar-Related Glycemic Excursions in Patients With Type 1 Diabetes on MiniMed™ 780G Advanced Hybrid Closed Loop System

Background: Ramadan Iftar meal typically causes glucose excursions. Dipeptidyl peptidase-4 inhibitors increase serum concentrations of glucagon-like peptide-1 and thus, decrease blood glucose levels with low risk of hypoglycemia.

Aim: To investigate the efficacy and safety of vildagliptin as an add-on therapy among adolescents and young adults with type 1 diabetes mellitus (T1DM) on glucose excursions of Iftar Ramadan meals and glycemic metrics during advanced hybrid closed-loop (AHCL) treatment.

Study Overview

• Status: Completed
• Conditions: Time in Range
• Intervention / Treatment: Drug: Dipeptidyl peptidase-4 inhibitors

Detailed Description

Current management of people with type 1 diabetes mellitus (T1DM) on intensive insulin therapy recognizes carbohydrates as the most important determinant of postprandial glycaemia; hence, worldwide guidelines recommend carbohydrates counting for determining pre-prandial insulin doses. Currently, the insulin to carbohydrate ratio (ICR) is frequently used to calculate the meal insulin dose. However, ICRs are considered difficult, ineffective and inaccurate for some patient, with an estimation error of around 20% in adults demonstrating only modest improvements in glycated hemoglobin (HbA1c). This lack of effectiveness and the wide variability using ICRs suggests it should be improved upon.

However, there have been only a few randomized control studies that investigated the efficacy and safety of DPP-4 inhibitors as an add-on drug in patients treated with basal insulin. Therefore, we conducted a one-month randomized control trial to investigate the efficacy and safety of DPP-4 inhibitors as an add-on therapy among adolescents and young adults with T1DM on glucose excursions of Iftar Ramadan meals and glucometrics during AHCL treatment .

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11361
    • Nancy Elbarbary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• patients with type 1 diabetes (T1DM )for at least one year
• patients aged 12-27 years
• patients using MiniMed 780G AHCL system (Medtronic, Northridge, CA, USA) at least 6 months before the study
• patients with minimum daily insulin requirement of more than 8 units
• patients willingness and ability to adhere to the study protocol, access to the internet and a computer system that met requirements for uploading the study pump data.

Exclusion Criteria:

• patients with any microvascular or macrovascular complications
• pregnancy, lactation
• patients who had a point-of-care screening HbA1c >10.0% (86 mmol/mol)
• patients with hypoglycemic unawareness or recurrent severe hypoglycemic episode in the last 6 months prior to recruitment
• patients with recurrent DKA (more than 2 episodes in the previous 6 months).
• patients with any chronic medical condition, current use of medications (other than insulin) that are known to affect blood glucose level.
• patients who had prior adverse reactions to the adjunctive agent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dipeptidyl peptidase-4 inhibitors; Dipeptidyl peptidase-4 inhibitors with Iftar meal	Drug: Dipeptidyl peptidase-4 inhibitors; Dipeptidyl peptidase-4 inhibitors with Iftar meal
No Intervention: Control group; No Dipeptidyl peptidase-4 inhibitors intake with Iftar meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
peak postprandial plasma glucose (PPG) level in mg/dl	peak postprandial plasma glucose (PPG) level in mg/dl	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in range %	Time in range %	4 weeks

Collaborators and Investigators

• Sponsor: Ain Shams University

Publications and helpful links

General Publications

• Brown SA, Kovatchev BP, Raghinaru D, Lum JW, Buckingham BA, Kudva YC, Laffel LM, Levy CJ, Pinsker JE, Wadwa RP, Dassau E, Doyle FJ 3rd, Anderson SM, Church MM, Dadlani V, Ekhlaspour L, Forlenza GP, Isganaitis E, Lam DW, Kollman C, Beck RW; iDCL Trial Research Group. Six-Month Randomized, Multicenter Trial of Closed-Loop Control in Type 1 Diabetes. N Engl J Med. 2019 Oct 31;381(18):1707-1717. doi: 10.1056/NEJMoa1907863. Epub 2019 Oct 16.
• Wadwa RP, Reed ZW, Buckingham BA, DeBoer MD, Ekhlaspour L, Forlenza GP, Schoelwer M, Lum J, Kollman C, Beck RW, Breton MD; PEDAP Trial Study Group. Trial of Hybrid Closed-Loop Control in Young Children with Type 1 Diabetes. N Engl J Med. 2023 Mar 16;388(11):991-1001. doi: 10.1056/NEJMoa2210834.
• Dyson PA, Twenefour D, Breen C, Duncan A, Elvin E, Goff L, Hill A, Kalsi P, Marsland N, McArdle P, Mellor D, Oliver L, Watson K. Diabetes UK evidence-based nutrition guidelines for the prevention and management of diabetes. Diabet Med. 2018 May;35(5):541-547. doi: 10.1111/dme.13603.
• Brazeau AS, Mircescu H, Desjardins K, Leroux C, Strychar I, Ekoe JM, Rabasa-Lhoret R. Carbohydrate counting accuracy and blood glucose variability in adults with type 1 diabetes. Diabetes Res Clin Pract. 2013 Jan;99(1):19-23. doi: 10.1016/j.diabres.2012.10.024. Epub 2012 Nov 10.
• Lakshman R, Boughton C, Hovorka R. The changing landscape of automated insulin delivery in the management of type 1 diabetes. Endocr Connect. 2023 Jul 31;12(8):e230132. doi: 10.1530/EC-23-0132.

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2023
• Primary Completion (Actual): April 21, 2023
• Study Completion (Actual): April 21, 2023

Study Registration Dates

• First Submitted: August 26, 2023
• First Submitted That Met QC Criteria: August 26, 2023
• First Posted (Actual): September 1, 2023

Study Record Updates

• Last Update Posted (Actual): September 1, 2023
• Last Update Submitted That Met QC Criteria: August 26, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Dipeptidyl-Peptidase IV Inhibitors
• Other Study ID Numbers: Ain Shams University 232212

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No