Improving Outcomes with SGLT2 Cotransporter Inhibitors in Challenging T2DM Patients Part 1.
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Transcript of Improving Outcomes with SGLT2 Cotransporter Inhibitors in Challenging T2DM Patients Part 1.
•Efficacy of SGLT2 Inhibition in T2DM and Application to Clinical Practice: Approved Agents
Ele Ferrannini, MD
Department of Clinical & Experimental Medicine
University of Pisa
Pisa, Italy
Mean plasma glucose (mg/dL)
Reprinted with permission from Ferrannini E, et al. J Clin Invest. 2014;124:499-508.
A1C (%)
6.5 7.0 7.5 8.0 8.5
SGLT2i
baseline
Effect of SGLT2 Inhibitionon Glycosuria
Time (min)
0.0
1.0
6.0
5.0
4.0
3.0
2.0
7.0
8.0
-180 -120 -60 0 60 120 180 240 300
dose
Baseline Acute
SGLT2i
Chronic SGLT2i
Meal
Reprinted with permission from Ferrannini E, et al. J Clin Invest. 2014;124:499-508.
Effect of SGLT2i on Glycosuriain T2DM
Canagliflozin in Patients with T2DM Inadequately Controlled with Metformin + Sulfonylurea over 52 Weeks
LOCF, last observation carried forward; LS least squares; SE, standard error.
Vercruysse G, et al. Presented at the 49th EASD Annual Meeting; Barcelona, Spain; Sept, 2013. Abstract 934.
-0.75%(95% CI: -0.95, -0.55)
-0.97%(95% CI: -1.17, -0.77
Proportion of subjects who achieved A1C <7.0%: canagliflozin 100 mg, 39.4%; canagliflozin 300 mg, 52.6%; placebo, 18.7%
0.2
0
-.02
-.04
-.06
-.08
-1.0
-1.2
0 6 12 18 26 34
Time point (week)
42 52
Baseline 8.1
Canagliflozin 100 mg8.1
Canagliflozin 300 mg8.1
0.01%
- 0.96%
-0.74%
Placebo
LS mean change
Change in A1C (LOCF)
1.0
0.5
0
-0.5
-1.0
-1.5
-2.0
-2.5
0 6 12 18 26 34
Time point (week)
42 52
Baseline (mmol/L) 9.4
0.6mmol/L
-1.5mmol/L
-1.1mmol/L
LS mean change
-1.6 mmol/L(95% CI: -2.1, -1.1)
-2.1 mmol/L(95% CI: -2.6, 1.6)
Canagliflozin 100 mg9.6
Canagliflozin 300 mg9.3
Change in FPG (LOCF)Placebo
Reproduced with the permission of Janssen Research & Development, LLC
Canagliflozin Monotherapy in T2DM InadequatelyControlled with Diet + Exercise over 52 weeks
Stenlöf K, et al. Presented at the 49th EASD Annual Meeting; Barcelona, Spain; Sept, 2013. Abstract 935.
Parameter Canagliflozin 100 mg
Canagliflozin 300 mg
A1C change, % -0.81 (0.07) -1.11 (0.07)
% of subjects reaching A1C <7.0% 52.4 (3.9) 64.5 (3.7)
FPG change, mmol/L -1.5 (0.1) -2.2 (0.1)
Body weight % change -3.3 (0.3) -4.4 (0.3)
Systolic BP change, mm Hg -1.4 (0.8) -3.9 (0.8)
Diastolic BP change, mm Hg -0.4 (0.6) -0.7 (0.6)
Triglycerides, % change -2.0 (3.0) -2.1 (3.0)
HDL-C % change 11.1 (1.5) 14.7 (1.5)
LDL-C % change 6.3 (2.1) 11.2 (2.1)
LDL-C/HDL-C % change -3.1 (2.1) -0.1 (2.1)
Non–HDL-C % change 1.8 (1.7) 5.6 (1.7)
Canagliflozin Monotherapy in T2DM InadequatelyControlled with Diet + Exercise over 52 weeks
Stenlöf K, et al. Presented at the 49th EASD Annual Meeting; Barcelona, Spain; Sept, 2013. Abstract 935.
Parameter Canagliflozin 100 mg
Canagliflozin 300 mg
A1C change, % -0.81 (0.07) -1.11 (0.07)
% of subjects reaching A1C <7.0% 52.4 (3.9) 64.5 (3.7)
FPG change, mmol/L -1.5 (0.1) -2.2 (0.1)
Body weight % change -3.3 (0.3) -4.4 (0.3)
Systolic BP change, mm Hg -1.4 (0.8) -3.9 (0.8)
Diastolic BP change, mm Hg -0.4 (0.6) -0.7 (0.6)
Triglycerides, % change -2.0 (3.0) -2.1 (3.0)
HDL-C % change 11.1 (1.5) 14.7 (1.5)
LDL-C % change 6.3 (2.1) 11.2 (2.1)
LDL-C/HDL-C % change -3.1 (2.1) -0.1 (2.1)
Non–HDL-C % change 1.8 (1.7) 5.6 (1.7)
Canagliflozin Monotherapy in T2DM InadequatelyControlled with Diet + Exercise over 52 weeks
Stenlöf K, et al. Presented at the 49th EASD Annual Meeting; Barcelona, Spain; Sept, 2013. Abstract 935.
Parameter Canagliflozin 100 mg
Canagliflozin 300 mg
A1C change, % -0.81 (0.07) -1.11 (0.07)
% of subjects reaching A1C <7.0% 52.4 (3.9) 64.5 (3.7)
FPG change, mmol/L -1.5 (0.1) -2.2 (0.1)
Body weight % change -3.3 (0.3) -4.4 (0.3)
Systolic BP change, mm Hg -1.4 (0.8) -3.9 (0.8)
Diastolic BP change, mm Hg -0.4 (0.6) -0.7 (0.6)
Triglycerides, % change -2.0 (3.0) -2.1 (3.0)
HDL-C % change 11.1 (1.5) 14.7 (1.5)
LDL-C % change 6.3 (2.1) 11.2 (2.1)
LDL-C/HDL-C % change -3.1 (2.1) -0.1 (2.1)
Non–HDL-C % change 1.8 (1.7) 5.6 (1.7)
Canagliflozin in Patients with T2DM InadequatelyControlled with Metformin + Sulfonylurea over 52 weeks
Percentage change in body weight (LOCF)
-1.3%(95% CI: -2.1, -0.5)(-1.0 kg[95% CI: -1.8, -0.2])
-2.2%(95% CI: -3.0, -1.4)(-2.1 kg[95% CI: -2.9, -1.2])
0.5
0
-.05
-1.0
-1.5
-2.0
-2.5
-3.0
-3.5
-4.0
0 6 12 18 26 34
Time point (week)
42 52
PBO
Baseline (kg) 90.8
CANA 100 mg
93.5
CANA 300 mg
93.5
-0.9%(-1.0 kg)
LS mean% change
-2.2%(-2.0 kg)
-3.2%(-3.1 kg)
Reductions in diastolic blood pressure were -2.2, 1.7, and 0.7 mm Hg with canagliflozin 100 and 300 mg and placebo, respectively. Change in pulse rate were 0.9, -1.2 and -0.4 beats per minute with canagliflozin 100 and 300 mg and placebo, respectively.
2
1
0
-1
-2
-3
-4
-5
-6
-7
0 6 12 18 26 34
Time point (week)
42 52
Baseline (mmol/L)
PBO
130.1
CANA 100 mg
130.4 130.8
0.1mmHg
--2.9mmHg-3.7mmHg
CANA 300 mg
LS mean change
Change in systolic blood pressure (LOCF)
-3.0 mmHg(95% CI: -5.5, -0.5)
-3.7 mmHg(95% CI: -6.2, -1.3)
Vercruysse G, et al. Presented at the 49th EASD Annual Meeting; Barcelona, Spain; Sept, 2013. Abstract 934.Reproduced with the permission of Janssen Research & Development, LLC
Vercruysse G, et al. Presented at the 49th EASD Annual Meeting; Barcelona, Spain; Sept, 2013. Abstract 934.
Canagliflozin in Patients with T2DM Inadequately Controlled with Metformin + Sulfonylurea over 52 WeeksParameter* CANA 100 mg CANA 300 mg PBO
A1C change, % -0.74 (0.08) -0.96 (0.08) 0.01 (0.08)
Difference vs placebo -0.75 (-0.95, -0.55) -0.97 (-1.17, -0.77)
% of subjects reaching A1C <7.0%† 39.4 (3.9) 52.6 (4.1) 18.7 (3.2)
Difference vs placebo 20.7 (10.1, 31,2) 34.0 (23.3, 44.7)
FPG change, mmol/L -1.1 (0.2) -1.5 (0.2) 0.6 (0.2)
Difference vs placebo -1.6 (-2.1, -1.1) -2.1 (-2.6, -1.6)
Body weight % change -2.2 (0.3) -3.2 (0.3) -0.9 (0.3)
Difference vs placebo -1.3 (-2.1, -0.5) -2.2 (-3.0, -1.4)
Systolic BP change, mm Hg -3.7 (1.0) -2.9 (1.0) 0.1 (1.0)
Difference vs placebo -3.7 (-6.2, -1.3) -3.0 (-5.5, -0.5)
Diastolic BP change, mm Hg -2.2 (0.6) -1.7 (0.6) -0.7 (0.6)
Difference vs placebo -1.6 (-3.2, 0.1) -1.1 (-2.7, 0.5)
Triglycerides % change 8.5 (4.6) 6.7 (4.5) 4.7 (4.6)
Difference vs placebo 3.8 (-7.8, 15.4) 2.0 (-9.6, 13.6)
HDL-C % change 6.6 (1.3) 8.2 (1.3) 3.3 (1.3)
Difference vs placebo 3.2 (-0.1, 6.5) 4.9 (1.6, 8.2)
LDL-C % change 4.8 (2.8) 13.3 (2.8) 5.4 (2.8)
Difference vs placebo -0.6 (-7.7, 6.5) 7.9 (0.8, 15.0)
LDL-C/HDL-C % change -0.3 (2.7) 5.1 (2.8) 3.7 (2.7)
Difference vs placebo -4.0 (-10.8, 2.8) 1.4 (-5.4, 8.2)
Non–HDL-C % change 2.5 (2.1) 7.5 (2.1) 3.9 (2.1)
Difference vs placebo -1.5 (-6.9, 3.9) 3.6 (-1.8, 9.0)