Gemini trial coreg

Interventions: Participants were randomized to receive a 6. Open-label hydrochlorothiazide and a dihydropyridine calcium antagonist were added, if needed, to achieve blood pressure target. Main outcome measures: Difference between groups in mean change from baseline HbA1c following 5 months of maintenance therapy. Additional prespecified comparisons included change from baseline HbA1c in individual treatment groups, treatment effect on insulin sensitivity, and microalbuminuria.

Results: The 2 groups differed in mean change in HbA1c from baseline 0. The people who should not take Coreg include those with severe heart failure who are hospitalized in the intensive care unit. Also, people who require certain intravenous medications that help support their circulation inotropic medications should not receive Coreg.

Other people who should not take Coreg are those with asthma or other breathing problems, those with a very slow heartbeat or heart that skips a beat irregular heartbeat , those with liver disease and those who are allergic to Coreg.

Some common side effects associated with Coreg include shortness of breath, a slow heartbeat, weight gain, fatigue, hypotension, dizziness or faintness. People taking Coreg who have any of these symptoms should call their doctor. Additionally, if patients experience fatigue or dizziness, they should sit or lie down and avoid driving or hazardous tasks. People with diabetes should report any changes in blood sugar levels to their physician.

Contact lens wearers may produce fewer tears or have dry eyes. As with any medicine, patients taking Coreg should also first tell their doctor what other medications they are taking. We are excited to announce that FibromyalgiaTreating. All of the same great people, writers and editors but now with more firepower. We now have access to an enormous amount of additional research information from doctors and scientists.

Data from large outcome trials indicate that the level of glycemic control predicts cardiovascular events. A detailed description of the study design and statistical methods has been published elsewhere. Participants were men and women aged 36 to 85 years with documented type 2 DM and stage 1 or 2 hypertension. Antidiabetic treatment must have been stable for 3 months and antihypertensive treatment stable for 1 month, and include an angiotensin-converting enzyme ACE inhibitor or angiotensin II receptor blocker ARB.

All participants gave written informed consent, and the protocol and procedures were approved by the institutional review board of each participating center. All other antihypertensive medications were discontinued over a 2- to 4-week period. Randomized treatment assignment was communicated to sites by an automated interactive randomization and medication ordering system RAMOS, GlaxoSmithKline, Philadelphia, Pa that used a randomly permuted block of 5 in a carvedilol:metoprolol distribution and incorporated stratification to equalize ARBs and thiazolidinedione medications in the treatment groups to assign treatment by container number.

Commercial supplies of metoprolol tartrate and carvedilol were identically over-encapsulated, packaged, and labeled with unique container numbers. Target diastolic BP was 85 mm Hg or less for those participants with baseline diastolic BP of 90 to mm Hg and 80 mm Hg or less for those participants with baseline diastolic BP of 80 to 90 mm Hg.

A dose of On reaching target BP or the highest dose level, participants began 5 months of maintenance therapy. Maximum study length per participant was 35 weeks, including down-titration as necessary and safety follow-up. No longer term follow-up was planned. The primary outcome was the difference in change from baseline HbA 1c between groups following 5 months of maintenance therapy. Patients taking insulin were excluded from analyses of insulin or insulin resistance.

Lastly, 3 post hoc analyses performed were new use of statins and increases in HbA 1c of more than 0. All data are expressed as mean SD unless otherwise noted. The primary outcome of between-group difference of change in HbA 1c was assessed using an intention-to-treat analysis. In addition, 2 principal secondary hypotheses were tested: metoprolol worsens glycemic control and carvedilol does not, as measured by change in HbA 1c.

Sample size calculation was based on detecting a difference for the primary outcome of 0. Assuming an SD of 1. Assuming a HbA 1c change from baseline of —0. The primary analysis for treatment group difference in HbA 1c change from baseline was based on analysis of covariance, adjusting for treatment group, baseline HbA 1c , ARB use, and thiazolidinedione use.

Because the trial began as 2 simultaneous identical studies one including sites from eastern United States and the other from western United States per Food and Drug Administration requirement, an effect for study was also included. When recruitment for one area of the country became very slow, it was decided to combine the 2 studies and forego seeking approval for a new indication so that 1 adequately powered study would address the hypothesis.

The treatment-by-study and treatment-by-thiazolidinedione interactions were tested and found to be nonsignificant. Because baseline use of ARBs and thiazolidinediones were stratification factors, they were retained in the model. A multivariate analysis of covariance was performed to consider effects of factors on HbA 1c change from baseline.

The covariates of interest included baseline HbA 1c , study, and treatment group; baseline use of thiazolidinediones, ARBs, statins, hydrochlorothiazide, and calcium antagonist use during the study; race white, black, or other declared by the participant ; sex; and end of study treatment dose level.

Race was assessed in the study to determine the distribution of the cohort studied and not to test an a priori hypothesis.

Interactions of treatment with hydrochlorothiazide, race, statin, and dose level were also included. Lastly, post hoc analyses to evaluate the percentage of participants who had more than 0. These analyses corrected for baseline HbA 1c , treatment randomization, thiazolidinedione, ARB, hydrochlorothiazide, age, sex, and statin use. An additional post hoc analysis evaluated use of statins in the 2 groups. For secondary outcomes, all continuous variables were analyzed via analysis of covariance using a similar model as specified for the primary efficacy parameter.

Analysis of binary variables was based on logistic regression with a model adjusting for treatment group, study, and baseline HbA 1c , and ARB and thiazolidinedione use. Analyses were based on a modified intention-to-treat efficacy population defined as participants randomized with valid baseline and at least 1 on-therapy assessment.

Change from baseline was calculated only for participants with both baseline and at least 1 on-therapy measurement. Results were based on analysis at maintenance month 5 visits for all variables, with missing values imputed using last observation carried forward analysis. In addition, a true intention-to-treat analysis was performed that included all existing data from all participants using last observation carried forward. Because there was only 1 specified primary parameter, no adjustments were made for multiple comparisons.

Summaries of safety data included all randomized participants. Patient demographic characteristics at study entry were similar Table 1. Diabetes mellitus was well-controlled mean baseline HbA 1c , 7. The mean doses required to achieve target BP were No difference in the proportion of each group that required The mean difference between carvedilol and metoprolol with respect to the change in HbA 1c from baseline was 0.

Carvedilol treatment had no effect on HbA 1c mean [SD] change from baseline to end point, 0. More participants withdrew due to worsening glycemic control in the metoprolol group 16 [2. Additionally, HOMA-IR was reduced by carvedilol and increased with metoprolol Table 3 , which resulted in a significant improvement from baseline for carvedilol —9.

Blood pressure and heart rate were similarly controlled in both groups Table 3. More participants had a statin initiated or existing statin dose increased in the metoprolol group 32 [4. In a second post hoc analysis, the proportion of participants with an increase in HbA 1c of at least 0.

Multivariate analysis tested for an interaction with each of the following covariates: baseline HbA 1c , treatment group, race, sex, baseline thiazolidinedione or ARB, and on-treatment hydrochlorothiazide, calcium antagonist, or statin, and found no significant interactions Table 4.

No differences were observed between groups in overall safety profile Table 5. Significant weight gain was observed in the metoprolol group mean [SD], 1. Structured surveillance of hypoglycemic episodes using patient diary recordings revealed that both asymptomatic and symptomatic episodes occurred in similar percentages of participants receiving carvedilol and metoprolol.

Three participants 0. Bradycardia was more frequent in the metoprolol group than in the carvedilol group. A total of 19 participants 3. In the carvedilol group, 6 participants had 7 cardiac events recorded, of which 2 were acute myocardial infarction; in the metoprolol group, 7 participants had events recorded, of whom 1 had acute myocardial infarction.

Metabolic events were recorded for 1 participant in the carvedilol group vs 3 in the metoprolol group. Two participants had 3 nervous system events reported in the carvedilol group vs 6 in the metoprolol group; 1 participant in each group had a stroke. No participant taking carvedilol had a respiratory event in contrast with 7 events in 6 participants taking metoprolol.

One report of gangrene was made in the carvedilol group. Three participants died, 1 taking carvedilol and 2 taking metoprolol; none were taking the study drug at the time of death. The participant taking carvedilol died of gastric cancer 39 days after stopping medications.