Differential effect of beta-blocker therapy on insulin resistance as a function of insulin sensitizer use: results from GEMINI.
OBJECTIVE
To determine whether the beneficial effects of carvedilol on insulin resistance (IR) are affected by the concomitant use of insulin sensitizers [thiazolidinediones (TZDs) and metformin].


METHODS
Changes in HbA1c and homeostasis model assessment-insulin resistance (HOMA-IR) were assessed over 5 months, comparing carvedilol with metoprolol tartrate according to insulin sensitizer (TZDs and metformin) use.


RESULTS
In TZD/metformin users, carvedilol patients showed a 5.4% decrease [95% confidence interval (CI) -11.9, 1.6; P = 0.13] and metoprolol tartrate patients showed a 2.8% decrease (95% CI -8.5, 3.2; P = 0.35) in HOMA-IR. The -2.6% difference between treatments was not significant (95% CI -10.7, 6.2; P = 0.55). In contrast, those not taking TZD/metformin experienced a 13.2% increase in HOMA-IR on metoprolol tartrate (95% CI 3.2, 24.1; P < 0.01) and a 4.8% decrease in HOMA-IR on carvedilol (95% CI -14.6, 6.0; P = 0.37), with a significant treatment difference of -15.9% favouring carvedilol (95% CI -26.6, -3.6; P = 0.01). There was no significant treatment interaction for the use of TZD/metformin and HbA1c. A statistically significant treatment difference was observed for HbA1c after 5 months favouring carvedilol after adjusting for insulin sensitizer use (-0.11%, 95% CI -0.214, -0.009; P = 0.03).


CONCLUSIONS
In patients with diabetes and hypertension not taking insulin sensitizers, the use of metoprolol tartrate resulted in a worsening of insulin resistance, an effect not seen with carvedilol. However, in TZD/metformin users the difference between the beta-blockers was not statistically significant.
Fonseca
V
V
Tulane University, New Orleans, LA 70112, USA. vfonseca@tulane.edu
Bakris
G L
GL
Bell
D S H
DS
McGill
J B
JB
Raskin
P
P
Messerli
F H
FH
Phillips
R A
RA
Katholi
R E
RE
Wright
J T
JT
Waterhouse
B
B
Lukas
M A
MA
Anderson
K M
KM
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D002227:Carbazoles / Q000627:therapeutic use; D000077261:Carvedilol; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008790:Metoprolol / Q000627:therapeutic use; D008875:Middle Aged; D011412:Propanolamines / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D001786:Blood Glucose; D002227:Carbazoles; D011412:Propanolamines; D045162:Thiazolidinediones; D000077261:Carvedilol; D008687:Metformin; D008790:Metoprolol