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We appreciate the thoughtful comments by Goodarzi and Azziz concerning the results of our meta-analysis on metformin treatment in individuals at risk for diabetes mellitus.¹ We evaluated the metabolic effects of metformin treatment in subjects with and without known polycystic ovary syndrome (PCOS) who were at risk for diabetes. We report beneficial effects of metformin treatment on body mass index, fasting glucose, fasting insulin, calculated insulin resistance, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and the incidence of new-onset diabetes, with no significant difference in results seen for those with and without known PCOS.

As Goodarzi and Azziz point out, it would be helpful to see the results for the subgroup of subjects with known PCOS, in order to help clarify the metabolic benefits for these women. We now provide the results separately for the 2 subgroups (Table). Data on women with PCOS were pooled from 14 trials with 620 participants. Metformin treatment in women with PCOS resulted in statistically significant improvements in body mass index (−5.3%), fasting glucose (−2.6%), calculated insulin resistance (−19.7%), and HDL cholesterol (9.4%), compared with placebo or no treatment. Nonsignificant reductions in fasting insulin, LDL cholesterol, and triglycerides were seen in women with PCOS, which were of similar magnitude to those seen in subjects without known PCOS. Unfortunately, no trials provided data on the incidence of new-onset diabetes mellitus in women with PCOS.

Table. Effect of Metformin on Metabolic Parameters in Subjects at Risk for Diabetes, % Change: Subgroup Analysis for Subjects with and without Known Polycystic Ovary Syndrome

Metabolic Parameter	PCOS	No Known PCOS
Body mass index	−5.3%(CT,−7.2to−3.4%)	−5.4%(CT,−7.2to−3.5%)
	P<.00001⁎	P<.00001⁎
Fasting glucose	−2.6%(CT,−4.9to−0.3%)	−5.9%(CT,−7.9to−3.9%)
	P=.03⁎	P<.00001⁎
Fasting insulin	−5.7%(CT,−19.3to7.8%)	−16.1%(CT,−22.1to−10.2%)
	P=.4	P<.00001⁎
Calculated insulin resistance	−19.7%(CT,−31.7to−7.6%)	−22.7%(CT,−27.8to−17.5%)
	P=.001⁎	P<.00001⁎
HDL cholesterol	9.4%(CT,0.03to18.8%)	4.6%(CT,1.0to8.1%)
	P=.05⁎	P=.01⁎
LDL cholesterol	−6.3%(CT,−19.0to6.5%)	−5.6%(CT,−8.3to−2.9)
	P=.34	P<.00001⁎
LDL/HDL ratio	−13.3%(CT,−29.8to3.2%)	−7.8%(CT,−14.1to−1.5%)
	P=.1	P=.02⁎
Triglycerides	−11.9%(CT,−24.2to0.3%)	−4.0%(CT,−9.9to2.0%)
	P=.06	P=.19

Abbreviations: PCOS=polycystic ovary syndrome; HDL=high-density lipoprotein; LDL=low-density lipoprotein.

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Reference 

1. Salpeter SR, Buckley NS, Kahn JA, Salpeter EE. Meta-analysis: metformin treatment in persons at risk for diabetes mellitus. Am J Med. 2008;121(2):149–157
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