Actos And Metformin In Women With Polycystic Ovary
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Transcript of Actos And Metformin In Women With Polycystic Ovary
Actos and Metformin in women with Polycystic Ovary
Syndrome not optimally responsive to Metformin
Glueck CJ, Goldenberg NM, Wang P, Sieve L
ACTOS
• Used for the treatment of type 2 DM
• Insulin sensitizing agent (PPAR- γ receptor)
• Class C agent during pregnancy
OBJECTIVE:
• Assess efficacy-safety of Actos (45 mg/d, median 10 months) when added to antecedent metformin (2.55 g/d, median 12 months) and diet, in 15 women with polycystic ovary syndrome (PCOS) not optimally responsive to metformin and diet
DESIGN:
• Prospective open label study of treatment of PCOS with metformin-diet, Actos-metformin-diet
• Metformin-diet: 15 non-responsive vs 30 responsive women with PCOS for 12 months
• Actos-metformin-diet: 13 of the non-responsive women for 10 months compared to their antecedent 12 months on metformin+diet
• Setting: Outpatient clinical research center
PATIENTS:
• 15 oligo-amenorrheic women with PCOS not optimally responsive to metformin+diet (did not resume normal menses, did not lose weight, did not reduce hyperandrogenemia)
• 30 oligo-amenorrheic women with PCOS, matched by age and previous menstrual history, responsive to metformin+diet
INTERVENTIONS:• Diet (1500 calorie, 26% protein, 44%
carbohydrate [42% complex], 40% fat, polyunsaturated/saturate ratio 2/1) throughout
• Metformin (2.55 g/day) given to two cohorts of women (n =15 non-responsive, n = 30 responsive) for medians of 12, 13 months
• Actos (45 mg/d) added for median 10 months in 13 of the non-responsive women
Main Outcome Measures:
• Menstrual status
• Changes in sex hormones
• Insulin• Insulin resistance (IR), insulin secretion
by HOMA model
• Cholesterol
Actos-Metformin Results:
• In the 13 non-responsive women who took metformin + Actos for a median of 10 months, compared to metformin-diet alone:
• On Actos + metformin:
• DHEAS fell (200 to 160 ug/dl, p =. 0046), • Insulin fell (16 to 11 uU/ml, p =. 0007), IR fell (3.73 to
2.11, p =. 003), insulin secretion fell (221 to 125, p=.0005),
• HDL cholesterol rose (38 to 41 mg/dl, p=.033)
13 non-Responders on Met for 12 months vs on Met+ Actos for 10 months
251241 242
200
210
220
230
240
250
260
Weight
251221
125
50
150
250
HOMA B-cell Fx
Baseline on Met on Met+ Actos
2316.2
11
0
5
10
15
20
25
Insulin (uU/ml)
4.243.73
2.11
0
2
4
6
HOMA IR
Baseline on Met on Met+ Actos
184 200160
100
120
140
160
180
200
DHEAS(ug)/dl)
P=.15 P=.34P=.24
P=.0005
P=.47P=.0046
P=.15
P=.0034P=.033
P=.0007
Results: Menstrual Status
• Non-responders: Versus 14% at pre-treatment baseline, at 3, 6, 9, and 12 months on metformin, 46% (p=.042), 38% (p=.03), 27%, and 24% of expected menses occurred
• Responders: Versus 12% at pre-treatment baseline, at 3, 6, 9, and 12 months on metformin, 75%, 81%, 88%, and 94% of expected menses occurred, p =. 036, =. 0009, .0007, <. 0001 compared to 15 non-responsive women
Menstrual Status on Actos-metformin
By paired comparison with metformin alone, 67% vs 46% of expected menses occurred at 3 months (p = .09), 77% vs 38% at 6 months (p = .004), 73% vs 27% at 9 months (p= .016)
Percent of menses occurring in women with PCOS
Comparison of 2 groups on Met
0
20
40
60
80
100
0 3 months 6 months 9 months 12months
% of
expe
cted m
ense
s
Responders Non-responders
Non-responders after Actos was added
0 months 3months 6 months 9 months
Non-responders
P=.094
.0039 .016
Responders better over 12 months p=0.0002 Non-responders
improved over
9 months P=.016