The effects of thiazolidinediones on blood pressure levels – A systematic review

Figures & data

Table I. Studies on subjects with components of the metabolic syndrome reporting effects of troglitazone on blood pressure levels.

Study (Ref.)	Type of subjects	n	Regimens compared	Duration	BP measurement	Mean effect on SBP/DBP vs baseline in Tro groups (mmHg)	IS or IR measurement
Kosaka K et al., J Clin Ther Med 1993 [51]	DM2, hyp	28	400 mg Tro vs plb	12 weeks	Office Bp	−16^a/−3	–
Nolan JJ et al., N Engl J Med 1994 [52]	Obese	18	400 mg Tro vs plb	12 weeks	Ambulatory BP	−5^a/−4^a	e‐h clamp
Ogihara T et al., Am J Hypertens 1995 [53]	DM2, hyp	18	400 mg Tro	8 weeks	Office BP	−9^a/−12^a	–
Ghazzi MN et al., Diabetes 1997 [54]	DM2	114	800 mg Tro vs Gly	48 weeks	Office BP	−1.9/−6.5^a	–
Tack CJ et al., Diabetologia 1998 [55]	Obese	15	400 mg Tro vs plb	8 weeks	Ambulatory BP	−0.8/−3.0^a	e‐h clamp
Imano E et al., Diabetes Care 1998 [60]	DM2	30	400 mg Tro vs 500 mg Met	12 weeks	Office BP	−3/0	–
Sung BH et al., Hypertension 1999 [56]	DM2	22	400 mg Tro vs 20 mg Gly	6 months	Office BP	−9^a/−6^a	–
Kawai T et al., Metabolism 1999 [57]	DM2	48	Diet+400mg Tro vs Sul+400mg Tro vs Diet+Diet	3 months	Office BP	−8^ba	–
Kawano Y et al., J Hypertens 2000 [59]	Overweight, hyp	30	400 mg Tro vs diet	8 weeks	Office BP, ambulatory BP	office: 0.8/0.8 ambulatory: 1.5/1.0	HOMA‐IR
Nakamura T et al., Diab Res Clin Pract 2001 [58]	Obese	29	200 or 400 mg Tro vs plb	12 weeks	office BP	−5^c/−1^c	–
Nakamura T et al., Diabet Med 2001 [61]	DM2	32	400 mg vs 5 mg Gli	12 months	Office SBP	−6^d
Watanabe K et al., J Hypertens 2004 [64]	Hyp	34	AT+400 mg Tro vs AT	6 months	Office BP	−7.4^a/−4.8^a	SSPG

SBP, systolic blood pressure; DBP, diastolic blood pressure; IS, insulin sensitivity; IR, insulin resistance; DM2, subjects with type 2 diabetes mellitus; hyp, subjects with hypertension; Tro, troglitazone; plb, placebo; Gly, glyburide; Met, metformin; Sul, Sulphonylurea; Gli, Glibenclamide; AT, antihypertensive treatment; e‐h clamp, euglycaemic–hyperinsulinaemic clamp; HOMA‐IR, homeostasis model assessment – insulin resistance index; SSPG, steady‐state plasma glucose. ^aSignificant change vs baseline levels or the other group compared. ^bChange of mean blood pressure in the Diet+Tro group vs baseline. ^cCombined data from the two troglitazone groups. ^dMean change for SBP vs baseline in both the groups of patients with micro‐ and macroalbuminuria.

Table II. Studies on subjects with components of the metabolic syndrome reporting effects of pioglitazone on blood pressure levels.

Study	Type of subjects	n	Regimens compared	Duration	BP measurement	Mean effect on SBP/DBP vs baseline in Pio groups (mmHg)	IS or IR measurement
Hirose H et al., Metabolism 2002 [85]	DM2	10	30 mg Pio	3 months	Office BP	−11^a/−6^a	–
Füllert S et al., J Clin Endocrinol Metab 2002 [86]	hyp	60	45 mg Pio vs plb	16 weeks	Office BP	−6.7/−7.9^a	e‐h clamp, HOMA‐IR
Gerber P et al., Curr Med Res Opin 2003 [87]	DM2, (hyp)^b	234	30 mg Pio vs 30 to 45 mg Pio vs 45 mg Pio	20 weeks	Office BP	−10^ac/−8^ac	–
Negro R et al., Minerva Endocr 2003 [88]	DM2, non‐dippers	40	30 mg Pio vs plb	8 weeks	Ambulatory BP	Daytime: −2.6/−2.8 night‐time: −5.3^a/−5.6^a	–
Nakamura T et al., J Diabetes Complications 2000 [92]	DM2	45	30mg Pio vs 5 mg Gli vs 0.6 mg Vog	3 months	Office BP	−6/−4	–
Nakamura T et al., Metabolism 2001 [93]	DM2	28	30mg Pio vs plb	6 months	Office SBP	−4^d	–
Satoh N et al., Diabetes Care 2003 [94]	DM2, (hyp)^b	136	30 mg Pio vs no additional treatment	3 months	Office BP	1/0	–
Belcher G et al., Int J Clin Pract 2004 [89]	DM2, (hyp)^b	3713	Pio vs Met or Gli^e	12 months	Office BP	−1.6^a/−1.4^a	–
Horio T et al., Am J Hypertens 2005 [90]	hyp	30	30 mg Pio	6 months	Office BP	0/−2^a	SSPG
Agarwal R et al., Kidney Int 2005 [95]	DM2, (hyp)^b	44	Pio vs Glip	4 months	Ambulatory BP	3.7/2.2	–
Dormandy J et al., Lancet 2005 [96]	DM2, (hyp)^b	5238	Pio vs plb	34.5 months	Office BP	−3^af/−2^f
Basu A et al., Diabetologia 2005 [Abstract] [91]	DM2	21	45 mg Pio vs 10 mg Glip	12 weeks	Office BP	−8.4^ag	–

SBP, systolic blood pressure; DBP, diastolic blood pressure; IS, insulin sensitivity; IR, insulin resistance; DM2, subjects with type 2 diabetes mellitus; hyp, subjects with hypertension; Pio. pioglitazone; plb, placebo; Met, metformin; Gli, Glibenclamide; Vog, Voglibose; Glip, Glipizide; e‐h clamp, euglycaemic–hyperinsulinaemic clamp; HOMA‐IR, homeostasis model assessment – insulin resistance index; SSPG, steady‐state plasma glucose. ^aSignificant change vs baseline levels or the other group compared. ^bA percentage of the total population was also hypertensive. ^cCombined data for hypertensive subjects from all the pioglitazone groups. ^dMean change for SBP vs baseline. ^eCombined data from 4 randomized, double‐blind studies comparing treatment with pioglitazone, metformin or gliclazide, either as monotherapy or as add‐on treatment on previous metformin or sulphonylurea therapy. ^fMedian change vs baseline. ^gMean change for DBP vs baseline.

Table III. Studies on subjects with components of the metabolic syndrome reporting effects of rosiglitazone on blood pressure levels.

Study	Type of subjects	n	Regimens compared	Duration	BP measurement	Mean effect on SBP/DBP vs baseline in Rosi groups (mmHg)	IS or IR measurement
St John Sutton M et al., Diabetes Care 2002 [106]	DM2, (hyp)^b	129	8 mg Rosi vs Gli	12 months	Ambulatory BP	−0.1^a/−2.3^a	–
Raji A et al., Diabetes Care 2003 [107]	hyp	24	8 mg Rosi	16 weeks	Ambulatory BP	−4^a/−5^a	e‐h clamp
Honisett S et al., Diabetes Care 2003 [109]	DM2, PW	31	4 mg Rosi vs plb	12 weeks	Office BP	−12^a/−6^a	–
Shargorodsky M et al., Am J Hypertens 2003 [108]	DM2, (hyp)^b	52	4 to 8 mg Rosi	6 months	Office BP	−20.1^a/−17.2^a	–
Wang TD et al., Am J Cardiol 2004 [110]	MS	50	4 mg Rosi vs plb	8 weeks	Office BP	−10^a/−7^a	–
Bennett SM et al., Diabet Med 2004 [111]	IGT, (hyp)^b	18	8 mg Rosi vs plb	12 weeks	Ambulatory BP	−7.0^a/−6.4^a	e‐h clamp
Natali A. et al., Diabetes Care 2004 [112]	DM2, (hyp)^b	74	8 mg Rosi vs 1500 mg Met vs plb	16 weeks	Ambulatory BP	−4/−2^a	e‐h clamp
Yosefy C et al., J Cardiovasc Pharmacol 2004 [113]	DM2, hyp	48	8 mg Rosi vs 10 mg Gli	8 weeks	Office BP	−6.1^a/−4.2^a	–
Sarafidis P et al., J Hypertens 2004 [114]	DM2, hyp	24	4 mg Rosi	6 months	Ambulatory BP	−5.4^a/−4.1^a	e‐h clamp HOMA‐IR
Kim YM et al., Diab Res Clin Pract 2005 [115]	DM2, (hyp)^b	125	4 mg Rosi vs no additional therapy	12 weeks	Office BP	−2.4/−2.9^a	HOMA‐IR, QUICKI
Negro R et al., Diab Res Clin Pract 2005 [116]	DM2, non‐dippers	38	8 mg Rosi vs plb	12 months	Ambulatory BP	Daytime: −3.4^a/−5.2^anight‐time: −5.1^a/−6.5^a	HOMA‐IR
Rosak C et al., Int J Clin Pract 2005 [117]	DM2, (hyp)^b	10,321	4‐8 mg Rosi	6 months	Office BP	−7^a/−3^a	–
Beck‐Nielsen H et al., Diabetologia 2005 [Abstract] [118]	DM2, (hyp)^b	668	Met+Rosi vs Met+Sulph and Sulph+Rosi vs Sulph+Met	12 months	Ambulatory BP	−4.8^a/−3.7^aand −3.8^a/−3.5^a	–
Ruilope LM et al., Diabetologia 2005 [Abstract] [119]	DM2, (hyp)^b	389	Met+Rosi vs Met+Gli	32 weeks	Ambulatory BP	−1.3^a/−2.3^a	–

SBP, systolic blood pressure; DBP, diastolic blood pressure; IS, insulin sensitivity; IR, insulin resistance; DM2, subjects with type 2 diabetes mellitus; IS, insulin sensitivity; IR, insulin resistance; hyp, subjects with hypertension; PW, postmenopausal women; MS, subjects with the metabolic syndrome; IGT, subjects with impaired glucose tolerance; Rosi, rosiglitazone; Gli, glibenclamide; plb, placebo; Met, metformin; Sulph, sulphonylurea; e‐h clamp, euglycaemic–hyperinsulinaemic clamp; HOMA‐IR, homeostasis model assessment – insulin resistance index; QUICKI, quantative insulin sensitivity check index. ^aSignificant change vs baseline levels or the other group compared. ^bA percentage of the total population was also hypertensive.

Figure 1. Funnel plots illustrating the relations between the effect of glitazones on systolic (A) and diastolic (B) blood pressure and the size of the glitazone group in each study. The plots include all reviewed studies in patients with components of the metabolic syndrome, with the exception of the papers of Belcher et al. [89] and Rosak et al. [117], which reported combined data from more than one original study, and the PROACTIVE study [96], where alterations in background antihypertensive treatment were permitted and blood pressure changes are reported as median values (SBP, systolic blood pressure; DBP, diastolic blood pressure; •, studies with troglitazone; □, studies with pioglitazone; ◊, studies with rosiglitazone). Weighted mean changes in the larger study (118) indicated by (‐‐‐‐‐).

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