Investigation of a Switch From Insulin Therapy to a Metformin & Saxagliptin Combination in Patients With Type 2 Diabetes Mellitus

The purpose of this study is to investigate the success rate of a switch from insulin therapy to a metformin & saxagliptin combination in patients with type 2 diabetes mellitus.

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Metformin and Saxagliptin

Detailed Description

The following study is based on a previous clinical trial performed at ikfe GmbH in Mainz in 2006 and 2007 (PIOswitch). [2] The purpose of this trial was to demonstrate that type 2 diabetes patients treated with insulin can be effectively switched to a pioglitazone/glimepiride combination without loss of glycemic control. The study was performed with 100 patients, out of whom 76 were finally successfully switched, resulting in a cheaper and more convenient therapy with indications of an improved laboratory cardiovascular risk biomarker profile (Hohberg et al., Diabetes Obes. Metab. 11:464-471, 2009). [2] Glimeperide is an agent with unspecific stimulating effect on the ß-cell and is considered to accelerate the progression of the disease while still controlling blood glucose. In addition, it may cause hypoglycemia. The combination of pioglitazone with glimepiride was selected, because pioglitazone requires approx. 5-6 weeks for developing its full anti-diabetic efficacy and an immediate effect on glucose was required to avoid glycemic deterioration.

It is tempting to speculate that the combination of a drug providing ß-cell protection (like saxagliptin) with a drug effectively and rapidly lowering blood glucose through a different mechanism of action (metformin) instead of unspecific ß-cell stimulation would result in an even improved outcome without risk of hypoglycemia. The purpose of this study is to investigate the success rate of a switch from insulin therapy to a metformin & saxagliptin combination in patients with type 2 diabetes mellitus.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Bochum, Germany, 44869
    • Diabetologische Schwerpunktpraxis Dr. Lorra / Dr. Bonnermann
  • Dresden, Germany, 01307
    • Zentrum für klinische Studien Dresden, GWT-TUD GmbH
  • Essen, Germany, 45355
    • Gemeinschaftspraxis Partner der Gesundheit
  • Mainz, Germany, 55116
    • IKFE Institute for Clinical Research and Development
  • Münster, Germany, 48145
    • Zentrum für Diabetes und Gefäßerkrankungen
  • Neuwied, Germany, 56564
    • Diabetes Zentrum Neuwied
  • Potsdam, Germany, 14469
    • ikfe Studiencenter Potsdam GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Combination of OAD and basal insulin treatment (BOT) or intensified conventional therapy (ICT; > 2 injections of basal and prandial) or conventional insulin therapy (CIT; 1 or 2 injections of basal or biphasic)
• HbA1c < 7.5 %
• Age: 18-80 years inclusively
• Duration of insulin therapy > 1 year
• Insulin dose < 120 IU/day
• Fasting C-peptide > 0.6 ng/l
• Fasting glucose ≤ 210 mg/dl
• Full legal, mental and physical ability to give informed consent
• Patient consent that the general physician will be informed of trail participation
• Experience in self measurement of blood glucose > 1 year

Exclusion Criteria:

• Type 1 Diabetes mellitus
• History of drug or alcohol abuse within the last five years prior to screening
• History of severe or multiple allergies
• Progressive fatal disease
• History of significant cardiovascular, respiratory, gastrointestinal, hepatic (ALAT and/or ASAT > 3 times the normal reference range), neurological, psychiatric and/or haematological disease as judged by the investigator
• Renal insufficiency or history of significant renal diseases (creatinine clearance lower than 60 ml/min determined using the Cockroft-Goult equation).
• Contra-indications for study drugs including contraindications for the rescue drugs
• Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures
• Pregnancy or breast feeding
• Sexually active women of childbearing potential not consistently and correctly practicing birth control by implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence or vasectomised partner
• Treatment with any other investigational drug within 3 months prior to screening
• Lack of compliance or other similar reason, that according to investigator, precludes satisfactory participation in the study

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
No Intervention: Control arm; The patients randomized to the control arm will continue their current therapy, as individually prescribed. Insulin will be administered via subcutaneous injection and OADs (if applicable) will be administered orally, as individually prescribed.
Experimental: Saxagliptin & metformin; Saxagliptin and metformin tablets will be administered orally. Pioglitazione (Rescue medication) tablets will be administered orally. Insulin glargine (Rescue medication) will be administered via subcutaneous injection as individually prescribed.	Drug: Metformin and Saxagliptin; Metformin 500mg/daily titrated to 2000mg/d in 4 Weeks (continued for 20 weeks) Saxagliptin 5 mg daily over complete trial

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
percentage of patients with stable HbA1c	26 ± 2 weeks (baseline to postbaseline values) at 4 week intervals

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
impact of the switch on:	- Biomarkers of insulin resistance and ß-cell function	26 ± 2 weeks (baseline to postbaseline values)
impact of the switch on:	- Biomarkers of cardiovaskular risk	26 ± 2 weeks (baseline to postbaseline values)
impact of the switch on:	- Patient treatment satifaction	26 ± 2 weeks (baseline to postbaseline values)
impact of the switch on:	- Treatment costs	26 ± 2 weeks (baseline to postbaseline values)
impact of the switch on:	- Requirement of 3rd line OAD pioglitazone as rescue drug	26 ± 2 weeks (baseline to postbaseline values)
impact of the switch on:	- oral Glucose Tolerance Test (oGTT)	26 ± 2 weeks (baseline to postbaseline values)
impact of the switch on:	- Macrophagen activation (in a subpopulation at site 01 ikfe GmbH)	26 ± 2 weeks (baseline to postbaseline values)

Collaborators and Investigators

• Sponsor: ikfe-CRO GmbH
• Collaborators: AstraZeneca; IKFE Institute for Clinical Research and Development
• Investigators: Principal Investigator: Andreas Pfützner, Prof.Dr.Dr., IKFE Institute for Clinical Research and Development

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Anticipated): February 1, 2011
• Study Completion (Anticipated): February 1, 2011

Study Registration Dates

• First Submitted: September 15, 2010
• First Submitted That Met QC Criteria: September 21, 2010
• First Posted (Estimate): September 22, 2010

Study Record Updates

• Last Update Posted (Estimate): September 22, 2010
• Last Update Submitted That Met QC Criteria: September 21, 2010
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Saxagliptin
• Other Study ID Numbers: AZ-SAX-001