Differences in Glucose Tolerance Between Fixed-Dose Antihypertensive Drug Combinations in People With Metabolic Syndrome
- George Bakris, MD1,
- Mark Molitch, MD2,
- Ann Hewkin, MSC3,
- Mark Kipnes, MD4,
- Pantelis Sarafidis, MD, PHD1,
- Kaffa Fakouhi, BSC3,
- Peter Bacher, MD, PHD3,
- James Sowers, MD5 and
- on behalf of the STAR Investigators *
- 1Department of Preventive Medicine, Rush University Hypertension Center, Chicago, Illinois
- 2Endocrine Division, Department of Medicine, Northwestern University Medical Center, Chicago, Illinois
- 3Department of Global Pharmaceutical Research and Development, Abbott, Abbott Park, Illinois
- 4Endocrinology Practice, San Antonio, Texas
- 5Endocrine Division, Department of Medicine, University of Missouri Medical Center, Columbia, Missouri
- Address correspondence and reprint requests to George Bakris, MD, Department of Medicine, Hypertension Unit, University of Chicago, Pritzker School of Medicine, 5841 S. Maryland Ave., MC 1027 Room M-267, Chicago, IL 60612. E-mail: gbakris{at}medicine.bsd.uchicago.edu
Abstract
OBJECTIVE—We sought to test the hypothesis that a fixed-dose combination of trandolapril/verapamil-SR (T/V) is superior to a fixed-dose combination of losartan/hydrochlorothiazide (L/H) on glucose tolerance in hypertensive patients with impaired glucose tolerance (IGT).
RESEARCH DESIGN AND METHODS—A prospective, randomized, open-label, blinded–end points design was used to assess the effects of a T/V versus L/H combination in patients with IGT and hypertension (n = 240) followed for up to 1 year. Doses were titrated to a systolic blood pressure <130 mmHg. Primary outcome was change from baseline in a 2-h glucose on oral glucose tolerance test (OGTT) at study end (mean [±SD] at follow-up, 46.9 ± 13.5 weeks). Secondary outcomes included changes in insulin sensitivity, office and 24-h ambulatory blood pressure, incidence of new-onset diabetes, lipids, and inflammatory markers. Data are expressed as means ± SE unless otherwise noted.
RESULTS—Changes at study end were noted in 2-h OGTT glucose (T/V −0.21 ± 0.36 vs. L/H +1.44 ± 0.36 mmol/l; P < 0.001) and insulin level (−30.13 ± 38.38 vs. +84.86 ± 38.33 pmol/l, respectively; P = 0.025). Worsening of insulin resistance occurred by week 12 (T/V 0.000 ± 0.001 vs. L/H −0.005 ± 0.001; P = 0.016). A higher incidence of new-onset diabetes (T/V 11.0 vs. L/H 26.6%; P = 0.002) and HbA1c >7% (2.6 vs. 9.6%, respectively; P = 0.05) occurred at study end.
CONCLUSIONS—In patients with IGT, normal kidney function, and hypertension, the fixed-dose combination of T/V reduces the risk of new-onset diabetes compared with an L/H-based therapy.
- DBP, diastolic blood pressure
- IGT, impaired glucose tolerance
- L/H, losartan/hydrochlorothiazide
- OGTT, oral glucose tolerance test
- RAS, renin angiotensin system
- SBP, systolic blood pressure
- STAR, Study of Trandolapril/Verapamil SR And Insulin Resistance
- TD, thiazide diuretic
- T/V, trandolapril/verapamil-SR
Footnotes
- *
↵* A complete list of the STAR Investigators can be found in the appendix.
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A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
DOI: 10.2337/dc06-1373. Clinical trial reg. no. NCT00234858, clinicaltrials.gov.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.
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- Accepted September 12, 2006.
- Received July 1, 2006.
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