slide 1 - uab - welcome - the university of alabama at birmingham
DESCRIPTION
TRANSCRIPT
![Page 1: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/1.jpg)
T2DM Control: Targeting Values or Targeting Patients?
Today’s speaker has no conflict of interest to disclose.
The University of Alabama School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical
education for physicians.
UAB School of Medicine designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit (s) Physicians should only claim credit
commensurate with the extent of their participation in the activity.
Gustavo R. Heudebert, MDDivision of General Internal Medicine
![Page 2: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/2.jpg)
Road Map
BackgroundDCCT and DCCT/EDICUKPDS and follow-up Interpreting RCT
Glycemic Control TrialsACCORD/ADVANCE/VADT
Targeting patients: systematic reviews and cohort study
Summary and recommendations
![Page 3: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/3.jpg)
DCCT
Randomized controlled trialType 1 diabetics; 1880 patients Intense versus conventionalA1C of 7.2% versus 9.1%
Decrease in microvascular complicationsRetinopathy (75% RRR)Peripheral neuropathy (60% RRR)Microalbuminuria (40% RRR)
Increase in hypoglycemic episodesDCCT Research Trial Group. NEJM 1993; 329: 977-86
![Page 4: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/4.jpg)
UKPDS Trial
Randomized controlled trialType 2 diabetics; 4000 patients Intense versus conventional control (diet)
A1C 7% versus 7.9%Sulfonylureas / insulinMetformin subgroup (> 120% IBW)
Decrease in microvascular complications (25% RRR)Photocoagulation for retinopathyUK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837-53
![Page 5: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/5.jpg)
UKPDS
Macrovascular complicationsFor sulfonylurea/insulin versus diet
RRR of 16% (0.052)For metformin versus diet
![Page 6: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/6.jpg)
DCCT / EDIC
Epidemiological studyFollow-up of DCCT patients
Length of follow-up: 6.5 yearsSimilar A1C control after 24 months
7.9% versus 8.2%Persistence of benefit
Retinopathy / Peripheral neuropathy / Microalbuminuria
DCCT/EDIC Research Group. NEJM 2000;342:381-9
![Page 7: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/7.jpg)
DCCT / EDIC
Seventeen years follow-upTrial from 1986-1993“Similar A1C” four years after termination of trial
Outcomes of interestCardiovascular disease (57% RRR)Stroke, non fatal MI, and death from
cardiovascular disease (42% RRR)
DCCT / EDIC Research Study Group. N Engl J Med 2005;353:2643-53
![Page 8: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/8.jpg)
![Page 9: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/9.jpg)
![Page 10: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/10.jpg)
UKPDS Follow-Up
Ten year follow-upSulfonylurea or insulinDietMetformin (> 120% body weight)
After one year post-trialSimilar levels of A1C
OutcomesMicrovascular / Macrovascular
![Page 11: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/11.jpg)
![Page 12: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/12.jpg)
![Page 13: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/13.jpg)
![Page 14: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/14.jpg)
![Page 15: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/15.jpg)
![Page 16: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/16.jpg)
Summary for Type 1 Diabetes
Short term improvement in microvascular outcomesRetinopathy / neuropathy / albuminuria
Long term maintenance in improved microvascular outcomes
Long term improvement in macrovascular outcomes
![Page 17: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/17.jpg)
Summary for Type 2 Diabetics
Improvement on composite outcome Mostly a reduction on the need for photocoagulation Near statistical significant reduction of myocardial
infarction Suggestion metformin beneficial
Long term outcomes Maintenance of microvascular outcomes Suggestion in improvement of macrovascular
outcomes
![Page 18: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/18.jpg)
RCT and Causality
Pinnacle of EvidenceBest suited to address hypothesis of difference
between interventions Intervention A “different” than Intervention B
“Statin lowers cholesterol more than niacin”
Ill suited to establish causality between intervention and outcome Intervention A explains certain outcome
“High Cholesterol is related to CAD”
![Page 19: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/19.jpg)
RCT and Causality
RCT reports an average effectDecrease in % CAD per mg decrease of LDL-C
Some patient derive benefit but other not If no downside to intervention clinically
unimportant
![Page 20: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/20.jpg)
![Page 21: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/21.jpg)
![Page 22: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/22.jpg)
![Page 23: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/23.jpg)
Summary
Risk for outcome of interest highly variable in RCT
Summary results do not address issue of patient variability
Multilevel risk assessment not done routinelyDifficult to apply “average” results from RCT
Potential for harm based on intervention
![Page 24: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/24.jpg)
VADT
Randomized controlled trialMulticenter trial among patients with T2DM1791 military veterans with poorly controlled
diabetes Intense versus conventional treatmentStratified by use of insulin, site, and prior
macrovascular eventGoal of 1.5% difference in A1C
Duckworth W et al. N Engl J Med 2009;360:129-139
![Page 25: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/25.jpg)
VADT
Composite MacrovascularAMI, stroke, death from CV disease, surgery for
CAD/CVA/PVD, new or worsening CHF, amputation for gangrene
MicrovascularIntervention
Two oral agents (based on BMI); addition of insulin to aim at A1C less 6% or less than 9%
Duration of 6 yearsDuckworth W et al. N Engl J Med 2009;360:129-139
![Page 26: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/26.jpg)
VADT
Age 60
Male 95%
Known CAD 40%
Duration of DM 11.5 years
Glycated Hgb 9.4%
Duckworth W et al. N Engl J Med 2009;360:129-139
![Page 27: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/27.jpg)
![Page 28: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/28.jpg)
![Page 29: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/29.jpg)
![Page 30: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/30.jpg)
![Page 31: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/31.jpg)
ACCORD Trial
Multicenter trial in US and CanadaSponsored by NHLBI77 centers across 7 networks
Participants10,251 patientsA1C greater than 7.5%Age 40 to 79 years
Age 55 to 79 if no CV event but with 2 risk factors
The ACCORD Study Group. N Engl J Med 2008;358:2545-2559
![Page 32: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/32.jpg)
ACCORD Trial
InterventionA1C less than 6% versus 7% to 7.9%More frequent follow-up in tight control groupRestricted formulary
CompositeNon fatal AMI, non fatal CVA, and death from
cardiovascular causesStudy stopped at 7th interim analyses
The ACCORD Study Group. N Engl J Med 2008;358:2545-2559
![Page 33: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/33.jpg)
ACCORD Trial
Age 62 years
Male 62%
Prior CAD 36%
Duration of DM 10 years
Glycated Hgb 8.3%
The ACCORD Study Group. N Engl J Med 2008;358:2545-2559
![Page 34: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/34.jpg)
![Page 35: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/35.jpg)
![Page 36: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/36.jpg)
![Page 37: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/37.jpg)
![Page 38: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/38.jpg)
Summary of RCT
No improvement in macrovascular outcomes with better A1C
Potential risk for harm (ACCORD)
Benefit for certain subgroups (?)
![Page 39: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/39.jpg)
Summary of RCT
Older patients with T2DM
Poor glycemic control
High cardiovascular risk profile
Long duration of disease
![Page 40: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/40.jpg)
Systematic Reviews
Two recent meta-analysis (2009)Lancet: five RCTs including the PROactive trialAnnals: five RCTs (UKPDS 33 and 34) but not
included PROactiveBoth studies included ACCORD, ADVANCE and
VADTBoth conducted rigorous literature searches
and analyses
Ray et al. Lancet 2009; 373:1765-72Kelly at al Ann Intern Med. 2009;151:394-403
![Page 41: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/41.jpg)
Systematic Reviews
Lancet Annals
Coronary Events 0.83 0.89
All CV Events 0.85 0.90
Strokes 0.93 0.98
Mortality 1.02 0.98
Ray et al. Lancet 2009; 373:1765-72Kelly at al Ann Intern Med. 2009;151:394-403
![Page 42: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/42.jpg)
Comorbidity and Outcomes
Observational study (1999-2004)Diabetics patients
Random sample from community based diabetes or general practices in Italy
No age, treatment. Or duration of diabetes restrictions
Main outcome: incident CV eventsAngina, AMI, CVA, TIA, CABG/PCI, lower limb
complications, and CV mortality
Greenfield et al. Ann Int Med 2009;151:854-860
![Page 43: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/43.jpg)
Cohort Study
Participating physicians collected the dataMeasure of comorbidity
Total Illness Burden IndexEight dimensions (CAD/CHF, COPD, CHF, OA/RA, etc.Dichotomized by degree of comorbidity (12) and if CV-
related or not
Incident CV outcomesTwo levels of A1C (< 6.5 and < 7%)
![Page 44: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/44.jpg)
Performance of TIBI
Survival at 5 yr Hazard Ratio
CV Events ( < 12) 83.7% 1.0
CV Events ( ≥ 12) 76.6% 1.52 (1.21-1.89)
Mortality ( < 12 ) 94.2% 1.0
Mortality (≥ 12 89.9% 1.39 (0.97-1.99)
![Page 45: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/45.jpg)
Analyses by A1C level
Hgb A1C level Hazard RatioUnadjusted
Hazard RatioAdjusted
TIBI Score ( < 12) 0.58 (0.41-0.82) 0.6 (0.42-0.85)
TIBI Score ( ≥ 12) 0.93 (0.68-1.26) 0.92 (0.68-1.25)
Hgb A1C (< 7%)
TIBI Score ( < 12) 0.59 (0.44-0.81) 0.61 (0.44-0.83)
TIBI Score ( ≥ 12) 0.88 (0.66-1.17) 0.86 (0.64-1.14)
![Page 46: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/46.jpg)
Summary
Comorbidity modulates the effect of glycemic control on outcomes
Lower comorbidity patients do benefit from tighter glycemic control
We need RCT to confirm above observationsWe need RCT to follow patients after trial
terminated in carefully defined risk groups
![Page 47: Slide 1 - UAB - Welcome - The University of Alabama at Birmingham](https://reader033.vdocuments.mx/reader033/viewer/2022061215/549f6d4dac79593d768b49f3/html5/thumbnails/47.jpg)
Final Recommendations
Tight glucose control in type 1 diabeticsBeneficial for microvascular complications
Have a legacy effectPossibly beneficial for macrovascular complications
Tight glucose control in type 2 diabeticsBeneficial for microvascular complications
Legacy effectBeneficial for macrovascular complications in
patients with few comorbidities