the ‘highs’ and ‘lows’ of sglt 2...
TRANSCRIPT
THE ‘HIGHS’ AND ‘LOWS’ OF SGLT-
2 INHIBITORS
Dr. Chiara Pretto, Dr. Naheed Mirebrahimi and Dr. David
Trachtenbarg
UICOMP
May 2017
A newer Diabetes
Mellitus medication
Sodium-Glucose co-
transport INHIBITOR
Prevents the
reabsorption of the
majority of glucose
filtered by the kidney (Hirsh and Peters) 1
Hypothesis
The HgbA1C reduction in clinical practice is comparable to
the HgbA1C reduction on the SGLT-2 Inhibitor package
inserts
Primary Outcome: To measure the reduction in HgbA1c
after starting SGLT -2 inhibitor therapy in adult patients at
UnityPoint Health
Secondary Outcomes: To measure weight reduction in our
study population
Design: Retrospective observational study though EPIC electronic
medical record
Inclusion: UnityPoint Health male and female diabetic patients greater
than 18 years old prescribed an SGLT-2 inhibitor
Exclusion: Patients initiated on an SGLT2 inhibitor with another DM
medication. Patients start and stop dates for an SGLT-2 inhibitor were
less than 90 days.
Statistical analysis: Paired one-tail and unpaired t-tests were used
for measuring HgbA1C and weight.
Of UnityPoint Health Adults (>18 yo) with Diabetes Mellitus,
6,417 patients were prescribed an SGLT-2 Inhibitor and
used it for 90 days +
Data collected from Spring 2013 to present
Females Males
Number 2774 3643
Average Age 58.3 58.6
RESULTS
Baseline
( +/- 1 mo)
3mo
(3-5 mo)
9mo
(6-12 mo)
HgbA1C 8.52% 7.67% 7.65%
Average Days from Baseline -2.9 108 234
HgbA1c change from baseline -0.85 -0.87
n 1078 1078 1078
Significance (Paired T-Test) <0.0001 <0.33 (NS)
7.15
7.43
7.70
7.98
8.25
8.53
Baseline 3 mo 9 mo
Reduction in HgbA1c
All HgbA1Cs While Patients on an SGLT-2
Days from Starting to 2 Years
Data Used for the Preliminary Analysis
Average
HgbA1C Reduction for Different SGLT-2 Medications
Baseline
( +/- 1 mo)
3mo
(3-5 mo)
9mo
(6-12 mo)
Canagliflozin 8.50% 7.61% 7.60%
Dapagliflozin 8.62% 7.77% 7.73%
Empagliflozin 8.42% 7.71% 7.67%
Significance (Unpaired T-Tests) NS NS NS
4.00
5.50
7.00
8.50
10.00
Baseline 3 mo 9 mo
Baseline
( +/- 1 mo)
3mo
(3-5 mo)
9mo
(6-12 mo)
Low dose 8.49% 7.66% 7.60%
High dose 8.58% 7.68% 7.67%
Significance by unpaired t-test 0.13 (NS) 0.69 (NS) 0.31(NS)
4.00
5.50
7.00
8.50
10.00
Baseline 3 mo 9 mo
HgbA1C Reduction
Low vs. High dose SGLT-2 Inhibitor Treatment
Change in baseline HgbA1c of -0.85 after 3 months
The 90-149 day reduction is highly significant, but no significant additional reduction between 150 - 360 days
No significant difference between approved SGLT-2 inhibitor medications
No significant difference between high vs. low dose treatments
Baseline
( +/- 1 mo)
3mo
(3-5 mo)
9mo
(6-12 mo)
Weight (lbs) 243.3 238.3 237.8
Average Days from Baseline -5.1 110 205
n 2355 2355 2355
Significance (Unpaired T-Test) <0.001 <0.37 (NS)
234.50
236.25
238.00
239.75
241.50
243.25
245.00
Baseline 3 mo 9 mo
Weight Reduction
Weight Reduction: Different SGLT-2 Medications
Baseline
( +/- 1 mo)
3mo
(3-5 mo)
9mo
(6-12 mo)
Wt on Canagliflozin (lbs) 243.8 239.1 238.4
Wt on Dapagliflozin (lbs) 244.2 238.5 238.7
Wt on Empagliflozin (lbs) 239.7 235.1 233.9
Significance (Unpaired T-Tests) NS NS
100.00
137.50
175.00
212.50
250.00
Baseline 3 mo 9 mo
Baseline
( +/- 1 mo)
3mo
(3-5 mo)
9mo
(6-12 mo)
Low Dose SGLT-2 (lbs) 238.5 233.2 233.3
High Dose SGLT-2 (lbs) 246.6 241.8 240.9
Significance (unpaired t-test) NS NS
100.00
137.50
175.00
212.50
250.00
Baseline 3 mo 9 mo
Weight Reduction: High dose vs. Low dose
Weight after discontinuation of SGLT2 Inhibitor
Baseline
( +/- 1 mo)
3mo
(3-5 mo)
9mo
(6-12 mo)
Weight (lbs) 232.3 233.2 233.9
Average Days from Baseline 7.2 109 194
n 738 738 738
Significance (paired T-Test) 0.76 (NS) <0.8 (NS)
100.00
137.50
175.00
212.50
250.00
Baseline 3 mo 9 mo
Average weight loss of ~5.0 lbs. after 90-149 days for all medications
90-149 day weight reduction is highly significant, but no significant additional reduction between 150 and 360 days
No significant difference in weight loss between the SGLT-2 Inhibitors
No significant weight change after discontinuation of SGLT-2 Inhibitor at 90-149 days or 150-360 days.
INVOKANA Package Insert:
“In patients with type 2 diabetes, treatment with INVOKANA produced clinically
and statistically significant improvements in HgbA1C compared to placebo.” 2
(Janssen Pharmaceuticals, Inc) 2
Invokana
Monotherapy
(26 wks)
Invokana with
Metformin
(26 wks)
Invokana with
Metformin &
Sulfonylurea
(26 wks)
Our study
(after 3 mo)
HgbA1c
(Change
from
baseline)
(-0.77 to -1.42) (-0.79 to -1.78) (-0.85 to -1.06) -0.85
Weight
Reduction
(%)
(-2.8 to -3.9) (-3.7 to -4.2) (-2.1 to -2.6) -2.06
Conclusion
Change in baseline HgbA1c of -0.85 after 3 months
Average weight loss of ~5.0 lbs. after 90-149 days for all medications
highly significant between 90-149 days
No significant difference between approved SGLT-2 inhibitor medications
The HgbA1C reduction in clinical practice is comparable to the
HgbA1C reduction on the SGLT-2 inhibitor package inserts
Patient selection
Patient compliance
Start and Stop dates of SGLT-2 Inhibitor by patient may be
different than Epic dates
Patient may have been prescribed SGLT-2 Inhibitor by
another provider not in Epic
Patients likely on other DM medications prior to SGLT-2
Inhibitor initiation
Lifestyle modifications
A prospective study
Determine the efficacy and side effects in different
ethnicities.
Explore more reasons for discontinuing medication
1. Hirsh, I.B, and Peters, A.L. SGLT-2 Inhibitors and Diabetic Ketoacidosis: What’s all the fuss about? Medscape. http://www.medscape.org/viewarticle/845828_transcript. June 25, 2015. Accessed May 17, 2017.
2. Janssen Pharmaceuticals, Inc. Invokana (Canagliflozin) tablets. https://www.invokana.com/prescribing-information.pdf. February 2017. Accessed May 16, 2017.
Dr. David Trachtenbarg- Research Guidance, Data mining
and Statistical analysis
Dr. Rahmat Na’Allah- Research Guidance
Emily Johnson, UICOMP Librarian & Assistant Professor-
Literature Research
UICOMP IRB