Approaches To Therapy Escalation In T2D

NCT03813316 | Withdrawn Phase 4

• 1 other identifier: 58214
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Type 2 diabetes mellitus (T2D) is a serious public health challenge which affects more than 9% of Canadians older than 20 years, an estimated prevalence that is anticipated to increase by over 40% in the next decade. The microvascular and macrovascular complications of T2D markedly increase the risks of hospitalization, heart disease, amputation, blindness, end stage renal disease and death, with profound socio-economic consequences for patients, families and society. Optimal glycemic control is fundamental to the management of T2D, as glycated hemoglobin (A1C) levels \> 7.0% are associated with a significantly increased risk of both microvascular and cardiovascular complications. But despite detailed clinical practice guidelines for management of hyperglycemia, glycemic control remains sub-optimal in a large proportion of patients. For example, in over 5000 Canadian diabetic patients managed by primary care physicians (PCPs), more than 50% had an A1C \> 7% and more than 20% an A1C \> 8%. For patients not achieving glycemic target on metformin monotherapy and without clinical CVD, Diabetes Canada 2018 Guidelines suggest that the preferred oral antihyperglycemic agents as add-on therapy be either DPP-4 inhibitors or SGLT2 inhibitors if avoidance of hypoglycemia and/or weight gain is a priority. Since most patients with type 2 diabetes would benefit from avoidance of hypoglycemia and/or weight gain, there is clinical rationale for adding DPP-4 inhibitors or SGLT2 inhibitors as oral therapy before considering other oral agents like sulfonylureas or thiazolidinediones. This study is designed to explore the possibility of improving care by providing more precise management guidance to primary care physicians when utilizing DPP-4 inhibitors or SGLT2 inhibitors as add-on therapy to metformin.

Conditions

Type2 Diabetes

Keywords

Diabetes; Type 2; T2D

Outcome Measures

Primary Outcomes (1)

• The percentage of participants achieving an A1C value of ≤ 7% at 24 weeks

  This study is designed to test the hypothesis that the provision of physician guidance and specialized training on utilizing DPP-4 inhibitors or SGLT2 inhibitors as add-on to metformin will result in more participants achieving glycemic target at Week 24 when compared to a usual care approach.

  24 Weeks

Secondary Outcomes (10)

• The percentage of participants achieving an A1C value ≤ 7% at 12 weeks

  12 weeks

• The absolute reduction in A1C from Baseline at 24 weeks

  Week 12 and Week 24.

• The percentage of participants requiring a change of therapy or rescue therapy at 12 weeks

  At 12 weeks

• Drug tolerability including percentage of participants with hypoglycemic events, and percentage with adverse events.events.

  24 weeks

• The absolute reduction in FPG from Baseline at 24 weeks

  24 weeks

Study Arms (2)

Interventional Arm

EXPERIMENTAL

Adding a DPP-4i (sitagliptin) and/or an SGLT2i (ertugliflozin) to metformin after receiving extra training on individualized care.

Drug: DPP-4 inhibitor; Drug: SGLT2 inhibitor; Drug: SGLT2 inhibitor and DPP-4 inhibitor

Control Arm

EXPERIMENTAL

Adding a DPP-4i (sitagliptin) and/or an SGLT2i (ertugliflozin) to metformin as per standard care/Diabetes Canada guidelines.

Drug: DPP-4 inhibitor; Drug: SGLT2 inhibitor; Drug: SGLT2 inhibitor and DPP-4 inhibitor

Interventions

DPP-4 inhibitor DRUG

Adding sitagliptin (DPP-4i) add-on using a fixed-dose combination with metformin (Janumet® 50/1000 mg BID).

Also known as: Sitagliptin

Control Arm; Interventional Arm

SGLT2 inhibitor DRUG

Adding ertugliflozin (SGLT2i) add-on using a fixed-dose combination with metformin(Segluromet® 2.5/1000 mg BID)

Also known as: Ertugliflozin

Control Arm; Interventional Arm

SGLT2 inhibitor and DPP-4 inhibitor DRUG

Adding both a DPP-4i as Fixed dose combination (Janumet) plus SGLT2i ertugliflozin (steglatro) as add-on to metformin.

Also known as: Ertugliflozin and Sitagliptin

Control Arm; Interventional Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18 years of age or older
• Previously diagnosed with T2D
• Have a glycated hemoglobin (A1C) result at Baseline between 7.1% and 9%
• Have an eGFR value at Baseline ≥60 ml/min/1.73m2
• Receiving stable (≥ 8 weeks) metformin at a dose of ≥1500 mg/day as monotherapy for T2D
• Ability to take oral medication and be willing to adhere to the study intervention regimen
• Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration
• No reason for investigator to suspect they will not tolerate the study medication

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Treated with antihyperglycemic agents other than metformin monotherapy.
• Known allergies or contraindications to the use of either DPP-4 inhibitors or SGLT2 inhibitors
• Presence of clinical evidence of cardiovascular disease including a history of heart failure, myocardial infarction, unstable angina, severe atherosclerotic cardiovascular disease on angiography, peripheral arterial disease and/or prior low extremity amputation, revascularization or stroke.
• Known pregnancy or current lactation
• Women of child bearing age not willing to use a method of contraception.
• Febrile illness within 30 days of signing informed consent
• Treatment with another investigational drug or other intervention within 90 days of signing informed consent
• Any physical or psychological condition(s) or diagnoses that in the opinion of the treating physician may preclude participation

Sponsors & Collaborators

• LMC Diabetes & Endocrinology Ltd.: lead
• Merck Sharp & Dohme LLC: collaborator
• Syreon Corporation: collaborator

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; ertugliflozin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• Ronald M. Goldenberg, MD

  LMC Clinical Research Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Model Description" by adding another sentence as follows: "Randomization with be cluster-based by investigator to either standard care or specific individualized training for adding DPP-4 inhibitors and/or SGLT2 inhibitors to metformin

Study Record Dates

• First Submitted: December 24, 2018
• First Posted: January 23, 2019
• Study Start: May 1, 2019
• Primary Completion: September 18, 2019
• Study Completion: September 18, 2019
• Last Updated: September 27, 2019

Record last verified: 2019-09