a. Thiazolidinediones and Metformin
b. Sulfonylureas, Insulin, and agents increasing levels of circulating incretins
c. Metformin only
d. Thiazolidinediones only

2. Insulin resistance is associated with increased likelihood of cardiovascular disease. Potential mechanisms include:

(i) hyperglycemia
(ii) hyperinsulinemia
(iii) dyslipidemia
(iv) hypertension
(v) hypercoagulability
(vi) inflammation

TZDs have been shown to favorably influence which of these abnormalities?

a. i, ii, and iii
b. iii, iv, and v
c. i, ii, iii, iv, v and vi
d. i only

3. True or False: Thiazolidinedione treatment has been shown to reduce carotid intima-media thickness, an indirect measure of atherosclerosis, and in clinical treatment has been shown to reduce the likelihood of restenosis following coronary artery angioplasty and stent placement.

a. True
b. False

4. The PROspective pioglitazone Clinical Trial In macroVascular Events (PROactive) included 5,238 diabetic individuals with CVD randomized to pioglitazone vs. conventional hypoglycemic therapy. The study found evidence of which of the following:

a. increased likelihood of congestive heart failure in persons receiving pioglitazone.

b. reduction in the combined rate of nonfatal myocardial infarction, nonfatal stroke, or CVD death (the principal secondary endpoint).

c. a non-significant reduction in the primary end point of a group of macrovascular complications of diabetes.

d. reduction in recurrent myocardial infarction among persons with prior myocardial infarction.

e. reduction in recurrent stroke among persons with prior stroke; reduction in blood pressure and reduction in glycemia.

f.  all of the above

5. True or False: Thiazolidinedione treatment has been shown to have protective effects on beta cells, to reduce the likelihood of progression from prediabetes to diabetes, and to increase the likelihood of sustained glycemic control in comparison to effects of metformin and of sulfonylureas.

a. True
b. False

6. At the time of approval of rosiglitazone, evidence was brought forward showing that likelihood of ischemic heart disease was, from greatest to least:

a. rosiglitazone > placebo > sulfonylureas > metformin
b. metformin > rosiglitazone > sulfonylureas > placebo
c. sulfonylureas > rosiglitazone > metformin > placebo
d. rosiglitazone > sulfonylureas > placebo > metformin

7. Nissen and Wolski, rosiglitazone reported a significant increase in risk of myocardial infarction after applying which of the following types of meta-analysis to the data?

a. Commonly used approaches to meta-analysis.
b. “Fixed effect” meta-analysis model.
c. “Random effect” meta-analysis model.

8. Problems with the analysis performed by Nissen and Wolski are:

a. Use of the “fixed effect” metaanalysis model, rather than the more conservative “random effect” model which shows a non-significant increase in myocardial infarction rate.

b. Failure to perform a literature search to identify all clinical trials of effect of rosiglitazone on myocardial infarction.

c. Failure to establish an a priori hypothesis for the metaanalysis.

d. Failure to take into account duration of follow-up, when available data suggest that persons randomized to rosiglitazone may have had consistently longer follow-up, perhaps because of superior glycemic control.

e. Exclusion of studies without events, rather than using standard approaches to including these studies in the analysis.

f. All of the above.

9. The Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) Study included 4400 diabetic individuals randomized to rosiglitazone vs. conventional hypoglycemic therapy. The study found evidence of:

a. increased likelihood of congestive heart failure in persons receiving rosiglitazone
b. a non-significant reduction in the combined rate of nonfatal myocardial infarction, nonfatal stroke, or CVD death
c. both ‘a’ and ‘b’
d. none of the above