A Study to Assess the Addition of Sitagliptin to Metformin Compared With the Addition of Dapagliflozin to Metformin in Participants With Type 2 Diabetes Mellitus (T2DM) and Mild Renal Impairment Who Have Inadequate Glycemic Control on Metformin With or Without a Sulfonylurea (MK-0431-838)

NCT02532855 | Completed Phase 3 Results

• 3 other identifiers: 0431-8382014-005525-13MK-0431-838
• Study Type: interventional
• Target: 614
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of the study is to assess the effect of the addition of sitagliptin to metformin with or without a sulfonylurea compared with the addition of dapagliflozin to metformin with or without a sulfonylurea on hemoglobin A1c (A1C) over 24 weeks of treatment as well as the overall safety and tolerability of sitagliptin in comparison to that of dapagliflozin after 24 weeks of treatment. The primary hypothesis is that the change from baseline in A1C in participants treated with the addition of sitagliptin is non-inferior compared to that in participants treated with the addition of dapagliflozin after 24 weeks of treatment.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in A1C at Week 24

  A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 24 A1C minus the Week 0 A1C.

  Baseline and Week 24

• Percentage of Participants Who Experienced One or More Adverse Events

  An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product. The AE does not have to have a causal relationship with this treatment. The AE can include any unfavourable and unintended sign, symptom, or disease or any worsening (change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the pharmaceutical product.

  Up to 26 weeks

• Percentage of Participants Who Discontinued Study Drug Due to an AE

  An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product. The AE does not have to have a causal relationship with this treatment. The AE can include any unfavourable and unintended sign, symptom, or disease or any worsening (change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the pharmaceutical product.

  Up to 24 weeks

Secondary Outcomes (7)

• Change From Baseline in Incremental 2-hour (2-hr) Postprandial Glucose Excursion (PPGE) at Week 24

  Immediately before and 120 minutes after the standard meal at Baseline and Week 24

• Change From Baseline in 2-hr Postprandial Glucose (PPG) at Week 24

  Immediately before and 120 minutes after the standard meal at Baseline and Week 24

• Change From Baseline in Glucagon Area Under the Curve (AUC0-120 Minutes) at Week 24

  Immediately before and 60 and 120 minutes after the standard meal at Baseline and Week 24

• Change From Baseline in Insulin AUC0-120 Minutes at Week 24

  Immediately before and 60 and 120 minutes after the standard meal at Baseline and Week 24

• Change From Baseline in Postprandial Insulin AUC0-120 Minutes to Glucagon AUC0-120 Minutes Ratio at Week 24

  Immediately before and 60 and 120 minutes after the standard meal at Baseline and Week 24

Study Arms (2)

Sitagliptin

EXPERIMENTAL

Participants receive sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 5 mg once daily for 4 weeks followed by sitagliptin 100 mg once daily plus matching placebo for dapagliflozin 10 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study.

Drug: Sitagliptin; Drug: Metformin; Drug: Matching placebo to dapagliflozin; Drug: Sulfonylurea

Dapagliflozin

ACTIVE COMPARATOR

Participants receive dapagliflozin 5 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 4 weeks followed by dapagliflozin 10 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study.

Drug: Dapagliflozin; Drug: Metformin; Drug: Matching placebo to sitagliptin; Drug: Sulfonylurea

Interventions

Sitagliptin DRUG

Sitagliptin 100 mg oral tablet

Sitagliptin

Dapagliflozin DRUG

Dapagliflozin 5 mg or 10 mg oral capsule. Up-titration to dapagliflozin 10 mg daily may be delayed if participant is unable to tolerate up-titration in the opinion of the investigator. Dapagliflozin 10 mg daily may be down-titrated to dapagliflozin 5 mg daily if participant is unable to tolerate the higher dose in the opinion of the investigator.

Dapagliflozin

Metformin DRUG

This medication is a standard-of-care medication and is administered in an open-label fashion. Supply of background metformin oral tablet(s) (at least 1500 mg daily) will be the responsibility of the participant throughout the duration of the study.

Dapagliflozin; Sitagliptin

Matching placebo to sitagliptin DRUG

Matching placebo to sitagliptin 100 mg oral tablet

Dapagliflozin

Matching placebo to dapagliflozin DRUG

Matching placebo to dapagliflozin 5 mg or 10 mg oral capsule. Up-titration to matching placebo to dapagliflozin 10 mg daily may be delayed if participant is unable to tolerate up-titration in the opinion of the investigator. Matching placebo to dapagliflozin 10 mg daily may be down-titrated to matching placebo to dapagliflozin 5 mg daily if participant is unable to tolerate the higher dose in the opinion of the investigator.

Sitagliptin

Sulfonylurea DRUG

This medication is a standard-of-care medication and is administered in an open-label fashion. The dose of the sulfonylurea agent will be required to be at least 50% of maximum labeled dose, consistent with near maximum efficacy of the sulfonylurea agent.

Dapagliflozin; Sitagliptin

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have T2DM at Screening visit
• Be on metformin monotherapy ≥1500 mg/day alone or in combination with an sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) for ≥8 weeks
• Is a male or a female not of reproductive potential (defined as one who is postmenopausal or has had a hysterectomy and/or bilateral oophorectomy, or had bilateral tubal ligation or occlusion at least 6 weeks prior to Screening visit). If participant is a female of reproductive potential, must agree to remain abstinent from heterosexual activity or agrees to use (or have her partner use) acceptable contraception to prevent pregnancy while receiving blinded study drug and for 14 days after the last dose of blinded study drug

You may not qualify if:

• Has a history of type 1 diabetes mellitus or a history of ketoacidosis
• Has a history of secondary causes of diabetes
• Has a known hypersensitivity or intolerance to any dipeptidyl peptidase IV (DPP-4) inhibitor or sodium-glucose cotransporter 2 (SGLT2) inhibitor
• Has been treated with any anti-hyperglycemic agents (AHA) other than metformin and for participants on dual combination therapy, a sulfonylurea within 12 weeks of screening
• Intends to initiate weight loss medication during the study period
• Has undergone bariatric surgery within 12 months of Screening visit
• Has started a weight loss medication or a medication associated with weight changes within the prior 12 weeks.
• Has a history of myocardial infarction, unstable angina, arterial revascularization, stroke, transient ischemic attack, heart failure within 3 months of Screening visit
• Has a history of malignancy ≤5 years prior to study, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
• Has human immunodeficiency virus (HIV)
• Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells, or clinically important hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
• Has a medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease
• Is currently being treated for hyperthyroidism or is on thyroid replacement therapy and has not been on a stable dose for at least 6 weeks prior to Screening visit
• Is on or likely to require treatment for ≥14 consecutive days or repeated courses of corticosteroids
• Is on or likely to require treatment for ≥7 consecutive days with non-steroidal anti-inflammatory drugs

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.

  PMID: 38770818 DERIVED

• Scott R, Morgan J, Zimmer Z, Lam RLH, O'Neill EA, Kaufman KD, Engel SS, Raji A. A randomized clinical trial of the efficacy and safety of sitagliptin compared with dapagliflozin in patients with type 2 diabetes mellitus and mild renal insufficiency: The CompoSIT-R study. Diabetes Obes Metab. 2018 Dec;20(12):2876-2884. doi: 10.1111/dom.13473. Epub 2018 Aug 16.

  PMID: 30019498 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sitagliptin Phosphate; dapagliflozin; Metformin; Sulfonylurea Compounds

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Biguanides; Guanidines; Amidines; Organic Chemicals; Urea; Amides; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2015
• First Posted: August 26, 2015
• Study Start: October 20, 2015
• Primary Completion: October 10, 2017
• Study Completion: October 10, 2017
• Last Updated: November 20, 2018
• Results First Posted: October 10, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share