|Key Question 1: For persons with type 2 diabetes, do pioglitazone and rosiglitazone differ from each other, from placebo, and from other oral hypoglycemic agents in the ability to reduce and maintain A1c levels?||Good||Pioglitazone compared to rosiglitazone: Prior systematic reviews:|
- Both drugs appear to have similar effects on A1c, producing a decrease of approximately 1%, similar to the change produced with other oral agents (including metformin, glibenclamide, or glimepiride).
5 head-to-head studies demonstrated no significant difference between pioglitazone and rosiglitazone on A1c.
- Indirect comparison demonstrated no difference between pioglitazone and rosiglitazone (difference: −0.13% (95% CI −0.41, 0.33)].
- In the longest duration pioglitazone trial (PROACTIVE, mean follow-up 34.5 months), both treatment groups optimized glycemic control with multiple oral agents. A1c change was −0.8% compared with baseline in the pioglitazone group; change ws −0.3% in the placebo groups.
- In the RESULT study, A1c change was maintained at 2 years with rosiglitazone compared to placebo with both groups receiving glipizide
Effect of both pioglitazone and rosiglitazone appears to be similar when used in either monotherapy or combination therapy.
<br>TZDs compared to other oral hypoglycemic agents: In a prior systematic review, there were no between-group differences between thiazolidinediones and metformin (7 randomized controlled trials) or second- generation sulfonylureas (13 randomized controlled trials).
Thiazolidinedione plus metformin compared with a second-generation sulfonylurea plus metformin (2 randomized controlled trials) did not show a consistent effect favoring 1 of the combinations, nor did 2 randomized controlled trials comparing thiazolidinediones with repaglinide.
One trial comparing pioglitazone to acarbose favored pioglitazone for A1c reduction.
|Key Question 2: For persons with type 2 diabetes, do pioglitazone and rosiglitazone differ from each other, from placebo, and from other oral hypoglycemic agents in their effects on macrovascular and microvascular complications, and mortality from diabetes?||Insufficient||Data are not sufficient to determine the comparative effectiveness of pioglitazone and rosiglitazone on microvascular or macrovascular complications of diabetes as there are no head- to-head data and indirect data are sparse.|
There are also insufficient data to show that either pio or rosi improves macrovascular complications relative to other oral diabetes agents or to placebo treatment.
There are no data on microvascular outcomes.
|Key Question 3 (NOT UPDATED): For patients with prediabetes or the metabolic syndrome, do thiazolidinediones differ from one another or from placebo in improving weight control when used as monotherapy?|
b. when added to metformin?
|Body of evidence is insufficient:|
- There are few studies examining the effect of Pio and Rosi in these populations on the outcomes of weight or abdominal obesity.
|- It is not possible to conclude whether there is a difference in weight change between Pio and Rosi.|
|Key Question 4: For persons with pre- diabetes or the metabolic syndrome, do pioglitazone and rosiglitazone differ from one another or from placebo in delaying or preventing the occurrence of type 2 diabetes?||Insufficient for the comparison of pio to rosi|
Insufficient for comparisons of thiazolidinediones to other oral hypoglycemic agents
Fair for rosiglitazone vs. Placebo
|There were insufficient data to determine whether pioglitazone and rosiglitazone have different effects on the incidence of diabetes among persons with either prediabetes or the metabolic syndrome.|
In a large, placebo-controlled trial (DREAM), the hazard ratio for risk of incident diabetes or death was 0.40 (95% CI 0.35 to 0.46; P<0.0001); the hazard ratio for death alone was 0.91 (95% CI 0.55 to 1.49; P =0.7) and for new onset type 2 diabetes 0.38 (95% CI 0.33 to 0.44; P<0.0001).
A smaller trial found a nonsignificant reduction in cases of new onset diabetes with rosiglitazone compared to placebo. (0% compared with 3.3%, P=0.08).
|Key Question 5: (NOT UPDATED) For patients with prediabetes or metabolic syndrome, is the use of different thiazolidinediones associated with reversal or slower progression of cardiac risk factors, including lipid levels, central obesity, or elevated blood pressure?||Body of evidence is insufficient|
- Four fair-quality studies provided data relevant to this question.
|- Data are insufficient to determine the comparative effectiveness of Pio and Rosi on cardiovascular risk factors among persons with prediabetes or the metabolic syndrome.|
- There were no data to address comparative effect on blood pressure.
- One fair-quality head-to-head study demonstrated improved lipid levels with pioglitazone compared to rosiglitazone.
- Data on both drugs from placebo-controlled trials showed mixed effects on lipid levels.
- Data on the effect of Pio and Rosi on weight and abdominal obesity are few and, as noted above in Key Question 3, it is not possible to conclude if there is a difference between the two drugs for these two outcomes.
|Key Question 6: For persons with type 2 diabetes what are the adverse events related to pioglitazone and rosiglitazone, and how do these differ from each other, from placebo, and from other oral hypoglycemic agents?||Good to fair||Adverse events occurring with pioglitazone and rosiglitazone were similar in 3 head-to-head trials.|
Withdrawals due to adverse events did not differ from placebo in trials of pioglitazone (difference from placebo 0%, 95% CI −2% to 2%) or rosiglitazone (−1%, 95% CI −3% to 0%).
The incidence of edema was greater for pioglitazaone and rosiglitazone than for placebo, with pooled risk differences from placebo of 4% for pioglitazone (95% CI 2% to 7%) and 8% for rosiglitazone (95% CI 3% to 13%).
|Key Question 7 (NOT UPDATED): How do thiazolidinediones compare to sulfonylureas in serious hypoglycemic events, functional status, and quality of life?||Body of evidence is insufficient|
- Four fair-quality studies were identified relevant to hypoglycemia and sulfonylureas
- There were no comparative data on functional status or quality of life from any efficacy or effectiveness trial which compared thiazolidinediones and sulfonylureas.
- 1 fair-quality study reported significantly fewer hypoglycemic events with Pio than with a sulfonylurea (P<0.05).
- Severe hypoglycemic episodes were not reported in any patient taking pioglitazone.
- The incidence of hypoglycemia was variable compared to a sulfonylurea (4 studies).
- Combination therapy (Rosi + various sulfonylureas or Rosi + glibenclamide) increased rates of hypoglycemia over sulfonylurea monotherapy (2 studies).
Functional status and quality of life
- No evidence upon which to draw conclusions
|Key Question 8: Are there subgroups of persons with type 2 diabetes based on demographic characteristics or comorbidities for which the benefits and adverse effects of pioglitazone or rosiglitazone differ from those in general populations, compared to each other an to other hypoglycemic agents?||Fair for demographic characteristics|
Poor for comorbidities and other characteristics
- The vast majority of studies were conducted in the United States or in Western Europe and examined Caucasian populations.
- Indirect evidence suggests that Pio and Rosi are equally effective among minority populations.
- No conclusions can be drawn as to which drug is more efficacious or effective, or associated with fewer side effects in population subgroups including olderaged persons.
- Analysis of secondary data suggest that both Pio and Rosi monotherapy are well-tolerated in older adults. Comorbidities and other characteristics
- No conclusions can be drawn on the comparative effectiveness of the 2 drugs under review among populations with significant comorbidities.