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Trial · Interventional

CompletedPhase 4Results postedRegistry data

FLuctuATion Reduction With inSULin and Glp-1 Added togetheR (FLAT-SUGAR)

Short name FLAT-SUGAR

Overview

Status
Completed
Phase
Phase 4
Enrollment
102 participants (actual)
Sponsor
University of Washington · Other
Design
Randomized · Double masking
Countries
1 country

United States

Start
Aug 2012
Primary completion
Jul 2014
Completion
Jul 2014
First posted
2 Feb 2012 (estimated)
Last update posted
29 Dec 2023
Conditions
Type 2 Diabetes

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2012201320142015
  1. Ph 4

    FLAT-SUGAR

    NCT01524705

    Aug 2012 to Jul 2014

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

Results of recent studies using standard long and short acting insulin therapy (Basal - Bolus or BBI) in type 2 diabetes mellitus (T2DM) have not shown benefits to lower risks for heart attacks, strokes, or eye, nerve and kidney problems. Some studies also show a long time between the start of treatment and signs of benefit. This has led to a review of current ways to normalize blood glucose control with basal bolus insulin and how to make blood glucose better. Improving blood sugar with insulin therapy usually causes weight gain, more high sugar levels after meals, and more low blood sugars. Early studies suggest that when people take long-acting insulin and metformin, they have fewer blood sugar extremes when they also take a new type of medicine called glucagon-like polypeptide-1 (GLP-1) agonist named exenatide (Byetta), instead of meal-time insulin. This means there might be a better way to treat Type 2 diabetes. Participants are asked to take part in an eight month study to find out if middle-aged and older people with Type 2 diabetes who have added risk factors for heart disease can even out their blood sugar levels. They will start on long-acting insulin, mealtime insulin, and metformin, if they are not already on these medications. Their kidney function tests must be normal and they must not be allergic to metformin. Then, after a 2 month run-in phase, they must be willing to be assigned by chance into one of two groups. This means that they will have a 50/50 chance (like flipping a coin) of being in either group. Half of them will be started on the new medicine known as Byetta rather than the meal-time insulin and the other half will remain on the meal-time insulin during the next 6 months (26 weeks) to see which group has more steady blood sugars. They will be asked to use a continuous blood sugar monitoring system called DexCom. A sensor is inserted under the skin in the same areas the insulin is injected. The DexCom can check their blood sugars 24 hours of the day and night and will be worn until 7 days of recordings are collected. In the same 7 day period, they will also be asked to wear a Holter or Telemetry monitor that will record their heart beats and rhythm which will be compared to the blood sugar readings. They will also use home glucose meters to check their glucose levels about 3 to 4 times a day. The study will take place at 12 centers in the United States and enroll about 120-130 people.

Interventions

  • Insulin GlargineDrug
  • MetforminDrug
  • Prandial insulinDrug
  • ExenatideDrug

Arms2

  • Experimental

    Insulin Glargine, metformin, exenatide

    Approximately 60 Type 2 diabetes mellitus (DM) participants will be instructed on an American Heart Association/American Diabetes Association (AHA/ADA) meal plan. Insulin Glargine, metformin and exenatide will used as a combination strategy to control individual glycosylated hemoglobin level (HbA1Cs) between 6.7 and 7.3% throughout the trial. The use of exenatide makes this the intervention arm

  • Active comparator

    glargine, metformin, prandial insulin

    Approximately 60 type 2 DM participants will be instructed in AHA/ADA meal plan. Insulin Glargine, metformin and one of 3 prandial insulins will be used as combination strategy to control individual HbA1Cs between 6.7 and 7.3%. Prandial Insulins (aspart, glulisine or lispro). The use of the short acting insulins make this the control arm

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Coefficient of Variation at 26 Weeks Minus Coefficient of Variation at Baseline

    Time frame · At baseline, 6 months of intervention

    Registry description

    The change in the coefficient of variation (CV) of continuous glucose readings, as assessed by Continuous Glucose Monitoring (CGM)

Secondary outcomes(2)
  1. Number of Participants With Hypoglycemia

    Time frame · 26 weeks

    Registry description

    Severe hypoglycemia-documented glucose \<50mg/dl (participant journal), and hypoglycemic attacks requiring hospitalization, or treatment by emergency personnel.

  2. Weight Change During Trial

    Time frame · Baseline vs 26 weeks

    Registry description

    Weight in kg at 26 weeks minus weight at baseline.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· At baseline, 6 months of intervention

Coefficient of Variation at 26 Weeks Minus Coefficient of Variation at Baseline

GroupValue (percentage)Spread
Insulin Glargine, Metformin, Exenatide-2.437.89
Insulin Glargine, Metformin, Prandial Insulin0.445.50
Secondary and other outcome results(3)
Secondary outcomeCount of participants· 26 weeks

Number of Participants With Hypoglycemia

GroupValue (Participants)
Insulin Glargine, Metformin, Exenatide0
Insulin Glargine, Metformin, Prandial Insulin0
Secondary outcomeMean· Baseline vs 26 weeks

Weight Change During Trial

GroupValue (kg)Spread
Insulin Glargine, Metformin, Exenatide-4.83.3
Insulin Glargine, Metformin, Prandial Insulin0.73.3
Other pre specified outcomeMean· Baseline vs 26 weeks

HbA1C Levels

GroupValue (% of HbA1C)Spread
Insulin Glargine, Metformin, Exenatide7.10.6
Insulin Glargine, Metformin, Prandial Insulin7.20.6

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Insulin Glargine, Metformin, ExenatideDrug: Insulin Glargine Glargine-injectable, variable, QD, 6 months Drug: Metformin Metformin-oral, up to 1000mg, BID, 6 months Drug: Exenatide Injectable, 5mcg, BID, 6 months1 / 524 / 5246 / 52
Insulin Glargine, Metformin, Prandial InsulinDrug: Insulin Glargine Glargine-injectable, variable, QD, 6 months Drug: Metformin Metformin-oral, up to 1000mg, BID, 6 months Drug: Prandial insulin Aspart or glulisine or lispro0 / 505 / 5037 / 50

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • ResultFLAT-SUGAR Trial Investigators. Glucose Variability in a 26-Week Randomized Comparison of Mealtime Treatment With Rapid-Acting Insulin Versus GLP-1 Agonist in Participants With Type 2 Diabetes at High Cardiovascular Risk. Diabetes Care. 2016 Jun;39(6):973-81. doi: 10.2337/dc15-2782. Epub 2016 Apr 19. PMID 27208320
  • DerivedFLAT-SUGAR Trial Investigators; Probstfield JL, Hirsch I, O'Brien K, Davis B, Bergenstal R, Kingry C, Khakpour D, Pressel S, Branch KR, Riddle M. Design of FLAT-SUGAR: Randomized Trial of Prandial Insulin Versus Prandial GLP-1 Receptor Agonist Together With Basal Insulin and Metformin for High-Risk Type 2 Diabetes. Diabetes Care. 2015 Aug;38(8):1558-66. doi: 10.2337/dc14-2689. Epub 2015 Jun 11. PMID 26068865

Eligibility

Who could join, as posted.

Sex
All
Age
from 40 Years up to 75 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: 1. T2DM for \>12 months defined according to current ADA criteria 2. C-peptide \>0.5 ng/mL-after informed consent has been signed, samples will be drawn fasting and sent to a central lab 3. Participants must be on insulin therapy. Diabetes, Blood Pressure \& Lipid therapy must be stable (in both dose and agent) for ≥3 months (dose of any 1 drug has not changed by more than 2-fold, \& new agents not been added within the previous 3 months) 4. HbA1c 7.5-8.5% for enrollment 5. Age at enrollment (screening): 40-75 years (inclusive) when there is a history of cardiovascular disease (defined in 'a'), or 55 to 75 years (inclusive) when there is not a history of cardiovascular disease but 2 or more risk factors (with or without treatment) are present (defined in 'b') a) Established cardiovascular disease defined as presence of one of the following: i. Previous myocardial infarction (MI). (most recent must be \> 3 months prior enrollment) ii. Previous stroke. (most recent must be \>3 months prior enrollment) iii. History of coronary revascularization (e.g., coronary artery bypass graft surgery, stent placement, percutaneous transluminal coronary angioplasty, or laser atherectomy)(most recent must be \> 3 months prior enrollment) iv. History of carotid or peripheral revascularization (e.g., carotid endarterectomy, lower extremity atherosclerotic disease atherectomy, repair of abdominal aortic aneurysm, femoral or popliteal bypass). (most recent must be \>3 months prior enrollment) v. Angina with either ischemic changes on a resting ECG, or ECG changes on a graded exercise test (GXT), or positive cardiac imaging study vi. Ankle/brachial index \<0.9 vii. LVH with strain by ECG or ECHO viii. \>50% stenosis of a coronary, carotid, renal or lower extremity artery. ix. Urine albumin to urine creatinine ratio of \>30 mg albumin/g creatinine in 2 samples, separated by at least 7 days, within past 12 months) \[Target of 50% of study cohort\] or b) Increased CVD risk defined as presence of 2 or more of the following: i. Untreated LDL-C \>130 mg/dL or on lipid treatment ii. Low HDL-C (\<40 mg/dL for men and \<50 mg/dL for women) iii. Untreated systolic BP \>140 mm Hg, or on antihypertensive treatment iv. Current cigarette smoking v. Body mass index 25-45 (Asian populations 23-45) kg/m2 6. No expectation that participant will move out of clinical center area during the next 8 months, unless move will be to an area served by another trial center 7. Ability to speak \& read English Exclusion Criteria: 1. The presence of a physical disability, significant medical or psychiatric disorder; substance abuse or use of a medication that in the judgment of the investigator will affect the use of CGM, wearing of the sensors, Holter or Telemetry monitor, complex medication regimen, or completion of any aspect of the protocol 2. Cannot have had any cardiovascular event or interventional procedure, (MI, Stroke or revascularization) or been hospitalized for unstable angina within the last 3 months 3. Inability or unwillingness to discontinue use of acetaminophen products during CGM use 4. Inability or unwillingness to discontinue use of all other diabetes agents other than insulin \& metformin during trial (including insulin pump participants who will need to convert to BBI) 5. Intolerance of metformin dose \<500 mg/day 6. Inability or unwillingness to perform blood glucose testing a minimum of 3 times/per day 7. Creatinine level ≥1.5 for males or 1.4 for females 8. ALT level ≥ 3 times upper limit of normal 9. Current symptomatic heart failure, history of NYHA Class III or IV congestive heart failure at any time, or ejection fraction (by any method) \< 25% 10. Inpatient psychiatric treatment in the past 6 months 11. Currently participating in an intervention trial 12. Chronic inflammatory diseases, such as collagen vascular diseases or inflammatory bowel disease 13. History of pancreatitis 14. BMI \>45kg/m2 15. For females, pregnant or intending to become pregnant during the next 7 months

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