Clinical trial NCT03076112: Efficacy of Ipragliflozin Compared With Sitagliptin in Uncontrolled Type 2 Diabetes With Sulfonylurea and Metformin
Official title: Efficacy of Ipragliflozin Compared With Sitagliptin in Uncontrolled Type 2 Diabetes With Sulfonylurea and Metformin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Keywords: Ipragliflozin
Sitagliptin
Lead sponsor: Seoul National University Bundang Hospital
Sponsor class: OTHER
Collaborators: name: Astellas Pharma Korea, Inc.
First posted: 2017-03-09
Enrollment: 170
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objectives of this study are 1) to compare the effect of ipragliflozin 50 mg on glucose-lowering effect with sitagliptin 100 mg in patients with type 2 diabetes mellitus, whose HbA1c level is ≥ 7.5% with sulfonylurea and metformin, 2) to investigate changes of other metabolic and cardiovascular risk factors such as triglyceride, HDL-cholesterol, uric acid, blood pressure, and inflammatory markers, 3) to examine changes of body composition including fat and muscle mass with volume status.

Detailed description: The objectives of this study are to compare the effect of 50mg of ipragliflozin, a SGLT2 inhibitor, on glucose-lowering effect with 100mg of sitagliptin, a DPP4 inhibitor in patients with type 2 diabetes mellitus, whose HbA1c level is ≥ 7.5% with sulfonylurea and metformin.

We are also going to investigate changes of other metabolic and cardiovascular risk factors such as triglyceride, HDL-cholesterol, uric acid, blood pressure, and inflammatory markers.

Changes of body composition including fat and muscle mass with volume status will be also examined.

Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes with HbA1c 7.5% - 9.0% at screening visit
* Male or female between 20 and 75 years of age
* Patients taking sulfonylurea (glimepiride 1\~8mg or gliclazide 30\~120 mg or equivalent dose) and metformin (≥ 1000 mg or maximum tolerated dose) for more than 3 months
* BMI ≥23 kg/m²
* Estimated GFR ≥ 60 ml/min/1.73m²
* Women of child bearing potential must take precautions to avoid pregnancy throughout the study and for 4 weeks after intake of the last dose and must have a negative urinary pregnancy test.

Exclusion Criteria:

* Type 1 diabetes, gestational diabetes, or diabetes with secondary cause
* Patients with acute coronary syndrome within 3 months prior to screening visit
* Patients with acute coronary syndrome within 3 months prior to screening visit
* Pregnant or breastfeeding women or reproductive-age women who refuse contraception
* Chronic hepatitis B or C (except healthy carrier of HBV), liver disease (AST/ALT \> 3-fold the upper limit of normal)
* Cancer within 5 years (except squamous cell cancer, cervical cancer, thyroid cancer with appropriate treatment) except thyroid cancer or carcinoma in situ
* Other clinical trials within 30 days
* Alcohol abuse
* Contraindication to SGLT2 inhibitors or Dipeptidyl-peptidase 4 inhibitors
* Taking insulin, oral hypoglycemic agents other than metformin, sulfonylurea, and the study drugs.

Primary outcomes:
measure: Glycated hemoglobin
timeFrame: Baseline, week 12, week 24
Secondary outcomes:
measure: Glycemic target goal achievement
timeFrame: Baseline, week 12, week 24
measure: Body weight
timeFrame: Baseline, week 12, week 24
measure: Body fat mass
timeFrame: Baseline, week 24
measure: Fasting plasma glucose level
timeFrame: Baseline, week 12, week 24
measure: Postprandial 2hr glucose level
timeFrame: Baseline, week 12, week 24
measure: Blood Pressure
timeFrame: Baseline, week 12, week 24
measure: Triglyceride/HDL-cholesterol ratio
timeFrame: Baseline, week 12, week 24
measure: Uric acid
timeFrame: Baseline, week 12, week 24
measure: Parathyroid hormone
timeFrame: Baseline, week 12, week 24
measure: 25-hydroxyvitamin D
timeFrame: Baseline, week 12, week 24
Other outcomes:
Locations:
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi
Study officials:
affiliation: Seoul National University Bundang Hospital
name: Soo Lim
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hedrington MS, Davis SN. Ipragliflozin , a sodium-glucose cotransporter 2 inhibitor, in the treatment of type 2 diabetes. Expert Opin Drug Metab Toxicol. 2015 Apr;11(4):613-23. doi: 10.1517/17425255.2015.1009893. Epub 2015 Feb 2.
citation: Kadokura T, Zhang W, Krauwinkel W, Leeflang S, Keirns J, Taniuchi Y, Nakajo I, Smulders R. Clinical pharmacokinetics and pharmacodynamics of the novel SGLT2 inhibitor ipragliflozin. Clin Pharmacokinet. 2014 Nov;53(11):975-88. doi: 10.1007/s40262-014-0180-z.
citation: Veltkamp SA, van Dijk J, Collins C, van Bruijnsvoort M, Kadokura T, Smulders RA. Combination treatment with ipragliflozin and metformin: a randomized, double-blind, placebo-controlled study in patients with type 2 diabetes mellitus. Clin Ther. 2012 Aug;34(8):1761-71. doi: 10.1016/j.clinthera.2012.06.027. Epub 2012 Jul 15.
citation: Takasu T, Hayashizaki Y, Tahara A, Kurosaki E, Takakura S. Antihyperglycemic effect of ipragliflozin, a sodium-glucose co-transporter 2 inhibitor, in combination with oral antidiabetic drugs in mice. Clin Exp Pharmacol Physiol. 2015 Jan;42(1):87-93. doi: 10.1111/1440-1681.12317.
citation: Smulders RA, Zhang W, Veltkamp SA, van Dijk J, Krauwinkel WJ, Keirns J, Kadokura T. No pharmacokinetic interaction between ipragliflozin and sitagliptin, pioglitazone, or glimepiride in healthy subjects. Diabetes Obes Metab. 2012 Oct;14(10):937-43. doi: 10.1111/j.1463-1326.2012.01624.x. Epub 2012 Jun 7.
citation: Macdonald FR, Peel JE, Jones HB, Mayers RM, Westgate L, Whaley JM, Poucher SM. The novel sodium glucose transporter 2 inhibitor dapagliflozin sustains pancreatic function and preserves islet morphology in obese, diabetic rats. Diabetes Obes Metab. 2010 Nov;12(11):1004-12. doi: 10.1111/j.1463-1326.2010.01291.x.
citation: Bolinder J, Ljunggren O, Johansson L, Wilding J, Langkilde AM, Sjostrom CD, Sugg J, Parikh S. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. 2014 Feb;16(2):159-69. doi: 10.1111/dom.12189. Epub 2013 Aug 29.
citation: Matthaei S, Bowering K, Rohwedder K, Grohl A, Parikh S; Study 05 Group. Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial. Diabetes Care. 2015 Mar;38(3):365-72. doi: 10.2337/dc14-0666. Epub 2015 Jan 15.
citation: Hermansen K, Kipnes M, Luo E, Fanurik D, Khatami H, Stein P; Sitagliptin Study 035 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab. 2007 Sep;9(5):733-45. doi: 10.1111/j.1463-1326.2007.00744.x. Epub 2007 Jun 26.