The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index; 4 of the 26 sources its claims cite were checked for support.
Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance
Open accessAbstract
BACKGROUND: Impaired glucose tolerance is associated with increased rates of cardiovascular disease and conversion to type 2 diabetes mellitus. Interventions that may prevent or delay such occurrences are of great clinical importance. METHODS: We conducted a randomized, double-blind, placebo-controlled study to examine whether pioglitazone can reduce the risk of type 2 diabetes mellitus in adults with impaired glucose tolerance. A total of 602 patients were randomly assigned to receive pioglitazone or placebo. The median follow-up period was 2.4 years. Fasting glucose was measured quarterly, and oral glucose tolerance tests were performed annually. Conversion to diabetes was confirmed on the basis of the results of repeat testing. RESULTS: Annual incidence rates for type 2 diabetes mellitus were 2.1% in the pioglitazone group and 7.6% in the placebo group, and the hazard ratio for conversion to diabetes in the pioglitazone group was 0.28 (95% confidence interval, 0.16 to 0.49; P<0.001). Conversion to normal glucose tolerance occurred in 48% of the patients in the pioglitazone group and 28% of those in the placebo group (P<0.001). Treatment with pioglitazone as compared with placebo was associated with significantly reduced levels of fasting glucose (a decrease of 11.7 mg per deciliter vs. 8.1 mg per deciliter [0.7 mmol per liter vs. 0.5 mmol per liter], P<0.001), 2-hour glucose (a decrease of 30.5 mg per deciliter vs. 15.6 mg per deciliter [1.6 mmol per liter vs. 0.9 mmol per liter], P<0.001), and HbA(1c) (a decrease of 0.04 percentage points vs. an increase of 0.20 percentage points, P<0.001). Pioglitazone therapy was also associated with a decrease in diastolic blood pressure (by 2.0 mm Hg vs. 0.0 mm Hg, P=0.03), a reduced rate of carotid intima-media thickening (31.5%, P=0.047), and a greater increase in the level of high-density lipoprotein cholesterol (by 7.35 mg per deciliter vs. 4.5 mg per deciliter [0.4 mmol per liter vs. 0.3 mmol per liter], P=0.008). Weight gain was greater with pioglitazone than with placebo (3.9 kg vs. 0.77 kg, P<0.001), and edema was more frequent (12.9% vs. 6.4%, P=0.007). CONCLUSIONS: As compared with placebo, pioglitazone reduced the risk of conversion of impaired glucose tolerance to type 2 diabetes mellitus by 72% but was associated with significant weight gain and edema. (Funded by Takeda Pharmaceuticals and others; ClinicalTrials.gov number, NCT00220961.).
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Claims the paper makes
36 Own result · 11 Own method · 8 No full text of the sources · 7 Own interpretation · 2 Partly supported · 1 Supported · 1 Couldn’t confirm · 1 Sources not found · 1 No basis given · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Because hyperglycemia plays a central role in the microvascular and macrovascular complications of diabetes, 3,5,6 it is possible that interventions that prevent or delay hyperglycemia may effectively prevent or delay these long-term complications.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > RESULTS
What the sources say
- Not checked — no full text of the sourcecites [3] source
- Not checked — no full text of the sourcecites [5] source
- Partly supportedcites [6] sourceExperimental — accuracy not yet measured
In the opening results passage (page unavailable), the paper says hyperglycemia plays a central role in microvascular complications of type 1 diabetes. A later results passage says differences in glycosylated hemoglobin accounted for much of the cardiovascular benefit of intensive therapy, supporting a role in macrovascular disease. The claim extends these type 1 findings to diabetes generally and states the macrovascular role more definitively than the paper does. (LLM, conf=0.83)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As compared with placebo, pioglitazone reduced the risk of conversion of impaired glucose tolerance to type 2 diabetes mellitus by 72% but was associated with significant weight gain and edema.”
- Also stated in: § Follow-up · plain
“The hazard ratio for development of diabetes in the pioglitazone group was 0.28 (95% confidence interval, 0.16 to 0.49; P<0.001).”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Abstract
plaindirectn = 303- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Follow-up · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Triglyceride levels declined significantly with pioglitazone (129±7.5 to 110±4.0 mg per deciliter [7.2±0.42 to 6.1±0.22 mmol per liter], P = 0.007) but not with placebo (124±4.6 to 113±4.0 mg per deciliter [6.9±0.25 to 6.30±0.22mmol per liter], P = 0.90); the difference between groups was not significant.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Triglyceride levels declined significantly with pioglitazone (129±7.5 to 110±4.0 mg per deciliter [7.2±0.42 to 6.1±0.22 mmol per liter], P = 0.007) but not with placebo (124±4.6 to 113±4.0 mg per deciliter [6.9±0.25 to 6.30±0.22mmol per liter], P = 0.90); the difference between groups was not significant.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As compared with placebo, pioglitazone reduced levels of both alanine aminotranferase and aspartate aminotransferase (P<0.001).”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Insulin sensitivity as measured with the Matsuda index increased more with pioglitazone than with placebo (4.31±0.24 to 7.65±0.34vs.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As compared with placebo, pioglitazone reduced levels of both alanine aminotranferase and aspartate aminotransferase (P<0.001).”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Triglyceride levels declined significantly with pioglitazone (129±7.5 to 110±4.0 mg per deciliter [7.2±0.42 to 6.1±0.22 mmol per liter], P = 0.007) but not with placebo (124±4.6 to 113±4.0 mg per deciliter [6.9±0.25 to 6.30±0.22mmol per liter], P = 0.90); the difference between groups was not significant.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As compared with placebo, pioglitazone reduced the risk of conversion of impaired glucose tolerance to type 2 diabetes mellitus by 72% but was associated with significant weight gain and edema.”
- Also stated in: § RESULTS · plain
“Weight gain was greater with pioglitazone than with placebo (3.9 kg vs. 0.77 kg, P<0.001)”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § RESULTS · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“HbA 1c (a decrease of 0.04 percentage points vs. an increase of 0.20 percentage points, P<0.001)”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > RESULTS
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 16
- It may state two separate claims as one. 18
- The quote only partly states this claim. 1
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“In one study, 9 the use of rosiglitazone decreased the risk of diabetes in adults with impaired glucose tolerance by 62%; given concerns about cardiovascular safety, 14 however, the Food and Drug Administration has restricted the use of rosig litazone therapy to patients in whom glycemic control cannot be achieved with other medications and who cannot take pioglitazone.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > RESULTS
What the sources say
- Could not verifycites [14] sourceExperimental — accuracy not yet measured
The Results report increased odds of myocardial infarction with rosiglitazone, supporting the cardiovascular-safety concern immediately preceding citation 14. But the supplied claim concerns an FDA restriction: the Discussion describes FDA approval criteria, not a restriction limiting rosiglitazone to patients who cannot use other medications or pioglitazone. Searches for those eligibility conditions found no supporting passage in our copy. (LLM, conf=0.76)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“The natural history of type 2 diabetes mellitus has been well defined, 4 starting with a genetic predisposition and progression from normal glucose tolerance with insulin resistance to impaired glucose tolerance and eventually type 2 diabetes mellitus with the superimposition of beta-cell failure.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > RESULTS
What the sources say
- Supportedcites [4] source
The “Natural History of Type 2 Diabetes” section describes inherited insulin resistance with initially normal glucose tolerance, progression from normal glucose tolerance to impaired glucose tolerance, and then overt diabetes as β-cell function declines. No page number is supplied in the passages. (LLM, conf=0.94)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Studies have shown that the rate of conversion of impaired glucose tolerance to type 2 diabetes mellitus is reduced with lifestyle modification 7 ; the use of metformin, 7 thiazolidinediones, [8][9][10][11] or acarbose 12 ; and bariatric surgery.13”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > RESULTS
What the sources say
- Not checked — no full text of the sourcecites [7] source
- Not checked — no full text of the sourcecites [8] source
- Not checked — no full text of the sourcecites [9] source
- Partly supportedcites [10] sourceExperimental — accuracy not yet measured
This citation is attached to the thiazolidinediones clause, not the other interventions. The Discussion reports that troglitazone reduced diabetes incidence by 75% during treatment, but explicitly says whether other thiazolidinediones are effective remains to be determined. It therefore supports troglitazone, not the class-wide claim without qualification. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [11] source
- Not checked — no full text of the sourcecites [12] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The number of people who would need to be treated to prevent one case of diabetes was 8 for 2.2 years of the trial and 18 for 1 year.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Follow-up
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During a median follow-up period of 2.4 years (mean, 2.2), diabetes developed in 50 of the 299 patients in the placebo group (16.7%) and in 15 of the 303 patients in the pioglitazone group (5.0%).”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Follow-up
plainn = 299- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Protection from diabetes with pioglitazone was of similar magnitude (with no significant heterogeneity) in subgroups defined by sex, age, weight, race or ethnic group, and fasting glucose level, as well as in patients with both impaired glucose tolerance and impaired fasting glucose and those with isolated impaired glucose tolerance (Fig. 3).”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Neither pioglitazone nor placebo altered levels of low-density lipoprotein cholesterol.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nine fractures occurred in 8 of the patients receiving pioglitazone (3%) and eight fractures occurred in 7 of the patients receiving placebo (2.6%) (Table 4 in the Supplementary Appendix).All fractures were associated with trauma.”
- Also stated in: § Discussion · plain
“Although an increased incidence of fractures has been reported with the use of thiazolidinediones, in this study, the incidence was similar in both groups, and all fractures were related to trauma.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Adverse Events
plainn = 8- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Events related to the cardiovascular system numbered 23 in the placebo group (7.7%) and 26 in the pioglitazone group (8.6%) (Table 3 in the Supplementary Appendix), with 1 case of congestive heart failure in each group (0.3%).”
- Also stated in: § Discussion · plain
“Physician-reported congestive heart failure developed in only one patient in each group.”
- Also stated in: § Discussion · plain
“For the comparison of placebo and pioglitazone regarding frequency of edema, cardiovascular events, and total events, P = 0.007, P = 0.80, and P = 0.03, respectively.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Adverse Events
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one. The quote only partly states this claim.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The ratio of urinary microalbumin to creatinine was low at baseline; during the study it fell slightly and similarly in the two groups (1.85±0.2 to 1.53±0.2mg per gram in the pioglitazone group vs. 1.47±0.3 to 1.25±0.3mg per gram in the placebo group, P = 0.20).”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although pioglitazone is a well-documented insulin sensitizer, insulin resistance was reduced according to the Matsuda index of insulin sensitivity measured during the oral glucose-tolerance test but not according to measurement of insulin sensitivity during the frequent-sampling intravenous glucose-tolerance test.”
- Also stated in: § Discussion · plain
“Insulin sensitivity as determined with the use of an intravenous glucose-tolerance test with frequent sampling in a subgroup of 191 patients was not altered in either group.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
plaindirectn = 191- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Pioglitazone was associated with lower diastolic blood pressure, higher levels of HDL cholesterol, and reduced rates of carotid intima-media thickening, as compared with placebo.”
- Also stated in: § Discussion · plain
“Use of pioglitazone improved diastolic blood pressure, HDL cholesterol levels, and serum levels of alanine aminotranferase and aspartate aminotransferase, and it slowed progression of carotid intima-media thickening.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“One unexplained sudden death oc-curred in the placebo group, and three deaths occurred in the pioglitazone group (one unexplained sudden death, one death from biliary carcinoma, and one death from a carcinoid tumor).”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Adverse Events
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Edema and weight gain were greater with pioglitazone than with placebo, as reported previously, 8,40 and edema largely accounted for the increase in adverse events associated with pioglitazone.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We calculated that enrollment of approximately 600 patients was required to achieve 90% power, if treatment with pioglitazone decreased the rate of conversion from impaired glucose tolerance to type 2 diabetes mellitus by 50%.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Statistical Analysis
plaindirectn = 600- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In one study, 9 the use of rosiglitazone decreased the risk of diabetes in adults with impaired glucose tolerance by 62%; given concerns about cardiovascular safety, 14 however, the Food and Drug Administration has restricted the use of rosig litazone therapy to patients in whom glycemic control cannot be achieved with other medications and who cannot take pioglitazone.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > RESULTS
What the sources say
- Not checked — no full text of the sourcecites [9] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, further glycemic separation between groups over time would presumably have a beneficial effect on microvascular disease.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Since neither approach produced statistically significant evidence of bias due to missing data, the primary and secondary analyses were performed without data imputation.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Takeda Pharmaceuticals provided financial support for the study but had no access to the data.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Study Design
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All results were transmitted to the Data Coordinating Center in Phoenix, Arizona, where they were recorded and audited and then sent to the Data Analysis Center in San Antonio.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Study Design
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The study was conducted in accordance with the protocol.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Study Design
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Troglitazone was reported to be associated with a 55% decrease in the rate of conversion to diabetes among women with prior gestational diabetes, 11 but this agent is no longer available.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > RESULTS
What the sources say
- Not checked — no full text of the sourcecites [11] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The small difference in levels of HbA 1c between the two groups is not surprising, given the low baseline level of HbA 1c in patients with impaired glucose tolerance.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The rate of adherence to the study regimen, assessed by means of pill counts, was greater than 80% in both groups.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Follow-up
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, if development of diabetic hyperglycemia can be delayed or prevented, it is plausible that the onset of microvascular complications might be slowed.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is not feasible to conduct studies of microvascular outcomes in patients with impaired glucose tolerance because of the large sample and long study duration required.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Loss to follow-up was relatively high in both study groups (24% in the placebo group and 30% in the pioglitazone group, not a significant dif-ference).”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Microvascular and macrovascular complications are common in type 2 diabetes mellitus and are related to both the severity and the duration of hyperglycemia. 3”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > RESULTS
What the sources say
- Not checked — no full text of the sourcecites [3] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We conducted a randomized, double-blind, placebo-controlled study to examine whether pioglitazone can reduce the risk of type 2 diabetes mellitus in adults with impaired glucose tolerance.”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > METHODS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“However, the greater the weight gain, the greater the improvements in betacell function and insulin sensitivity, and thus the greater the reduction in HbA 1c .26,35,36”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Carotid intima-media thickening is highly correlated with cardiovascular events, and changes in this measure over time have predictive value beyond that of standard markers of risk.18,38”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Discussion
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Impaired glucose tolerance is associated with increased rates of cardiovascular disease.
“Impaired glucose tolerance is associated with increased rates of cardiovascular disease and conversion to type 2 diabetes mellitus.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“There is strong evidence that oral glucose-lowering medications approved for DM reduce the progression of prediabetes to DM.888–896”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [890]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Metformin can also be combined with linagliptin to decrease DM incidence over that observed with metformin alone.890”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [890]
Experimental — accuracy not yet measuredIn the citing paper
“However, these hypotheses are based on results from the Swedish Obese Subjects Study in which subjects were not randomized and the control group was contemporaneously matched, only received conventional treatment, and differed by a number of characteristics at baseline.”
From Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future (2014) · cites this paper as [174]
In the citing paper
“Other studies have reported lower conversion rates29 (19% in controls in the DPP Outcomes study).15”
From Prediabetes: a high-risk state for diabetes development (2012) · cites this paper as [29]
In the citing paper
“Pioglitazone showed effectiveness in the ACT NOW Study on obese people with IGT. The risk of diabetes decreased by >70% and the drug was associated with improved diastolic blood pressure, improved HDL-cholesterol and a reduced rate of carotid intima-media thickening. However, weight gain was greater with pioglitazone (~3 kg compared to placebo) and edema was more frequently reported (13% vs. 6%).”
From Prediabetes: a high-risk state for diabetes development (2012) · cites this paper as [29]
In the citing paper
“In Actos Now for Prevention of Diabetes (ACT NOW), treatment with pioglitazone 45 mg per day reduced incident diabetes 72% over 2.4 years in patients with IGT and at least one other risk factor for T2DM and BMI ≥ 25 kg/m2.203”
From The Vasculature in Prediabetes (2018) · cites this paper as [203]
In the citing paper
“Thiazolidinediones prevent the development of diabetes in individuals with IFG or IGT.”
From The Vasculature in Prediabetes (2018) · cites this paper as [203]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“eight fractures occurred in 7 of the patients receiving placebo (2.6%)”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Adverse Events
Reported 2.6 · recomputed 2.341137
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Participants
“Mean BMI 33.0±0.434.5±0.40.44”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
“34.1±0.4 to 35.5±0.4,and 40.0±0.8 to 41.9±0.7%,respectively), but the increments were greater with pioglitazone”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“Triglyceride levels declined significantly with pioglitazone (129±7.5 to 110±4.0 mg per deciliter [7.2±0.42 to 6.1±0.22 mmol per liter], P = 0.007)”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
Reported 7.2 · recomputed 1.45641
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“The change in high-density lipoprotein (HDL) cholesterol was greater with pioglitazone (40±1 to 48±1 mg per deciliter [2.2±0.06 to 2.7±0.06 mmol per liter])”
§ Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance > Effects of Pioglitazone
Reported 2.2 · recomputed 1.0344
Citations
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Cardiovascular Risk Stratification and Management in Pre-Diabetes
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“Indeed, reducing the workload for a dysfunctional beta cell is more likely to produce durable glucose control [6, 13].”
Palmer, A. J., & Tucker, D. M. D. (2011) · Primary care diabetes · doi:10.1016/j.pcd.2011.10.006 · Cited by 53
Alternate therapy of Type 2 diabetes mellitus (T2DM) with Nigella (Ranunculaceae)
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“T2DM is manifestation of an autoinflammatory syndrome (Dinarello, 2011; Donath et al., 2008) which is usually associated with the state of low-grade inflammation in intra-islets (Holberg and Hotamisligil, 2006; Wellen and Hotamisligil, 2005).”
BackgroundEffects of pioglitazone therapy on blood parameters, weight and BMI: a meta-analysis
Filipova, E. P., Uzunova, K. H., Kalinov, K., & Vekov, T. Y. (2017) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-017-0290-5 · Cited by 54
“[16, 17] contemplated the use of pioglitazone for T2DM prevention in IGT and its influence on β-cell function.”
BackgroundMethodGlobal status of diabetes prevention and prospects for action: A consensus statement
Ibrahim, M., Tuomilehto, J., Aschner, P., Beseler, L., Cahn, A., Eckel, R. H., Fischl, A. H., Guthrie, G., Hill, J. O., Kumwenda, M., et al. (2018) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3021 · Cited by 52
“Pioglitazone, which showed a 72% relative risk reduction, was even more effective in reducing the incidence of T2D in subjects with prediabetes.(61) Recently, liraglutide treatment in individuals with prediabetes had also shown a large effect with a 66% relative risk reduction in the prevention of diabetes.”
BackgroundNesti, L., Mengozzi, A., & Tricò, D. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00144 · Cited by 53
Ranjit Unnikrishnan, I., Shaw, J. E., Chan, J. C. N., Wild, S. H., Peters, A. L., Orrange, S., Roden, M., & Mohan, V. (2025) · Nature Reviews Disease Primers · doi:10.1038/s41572-025-00635-0 · Cited by 69
“…various drugs 119,123,127,135–150 (Table 3), including metformin 97,150 , troglitazone 135,143 , acarbose 136,140 , orlistat 148 , pioglitazone 137 , rosiglitazone 138,150 , ramipril 139 , voglibose 142 , nateglinide 145 , valsartan 146 and liraglutide 144,147 , for the prevention of…”
Sex-specific differences in diabetes prevention: a systematic review and meta-analysis
Glechner, A., Harreiter, J., Gartlehner, G., Rohleder, S., Kautzky, A., Tuomilehto, J. O., Noord, M. V., Kaminski-Hartenthaler, A., & Kautzky‐Willer, A. (2014) · Diabetologia · doi:10.1007/s00125-014-3439-x · Cited by 56
“Only three of those, however, published sex-specific results [1, 20, 22, 40].”
BackgroundSmith, R. C., Jin, H., Li, C., Bark, N. M., Shekhar, A., Dwivedi, S., Mortiere, C., Lohr, J. B., Hu, Q., & Davis, J. M. (2012) · Schizophrenia Research · doi:10.1016/j.schres.2012.10.023 · Cited by 52
“…the conversion of impaired glucose to diabetes, with approximately 70% of patients showing this effect, has been reported in the ACT Now study (DeFronzo et al., 2011), and PIO's effect appears to be superior to metformin (2 studies of metformin report that 26–31% of patients had delay in…”
Young, L. H., Viscoli, C. M., Schwartz, G. G., Inzucchi, S. E., Curtis, J. P., Gorman, M., Furie, K. L., CONWIT, R. A., Spatz, E. S., Lovejoy, A. M., et al. (2018) · Circulation · doi:10.1161/circulationaha.118.034763 · Cited by 53
Health risks and interventions in prediabetes: A review
Mahat, R. K., Singh, N., Arora, M., & Rathore, V. (2019) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2019.07.041 · Cited by 56
MASLD/MASH and type 2 diabetes: Two sides of the same coin? From single PPAR to pan-PPAR agonists
Cooreman, M. P., Vonghia, L., & Francque, S. (2024) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2024.111688 · Cited by 55
Pioglitazone and vitamin E for nonalcoholic steatohepatitis: A cost utility analysis
Mahady, S. E., Wong, G., Craig, J. C., & George, J. (2012) · Hepatology · doi:10.1002/hep.25887 · Cited by 50
Viscoli, C. M., Brass, L. M., Carolei, A., Conwit, R., Ford, G. A., Furie, K. L., Gorman, M., Guarino, P. D., Inzucchi, S. E., Lovejoy, A. M., et al. (2014) · American Heart Journal · doi:10.1016/j.ahj.2014.07.016 · Cited by 50
Burris, T. P., de Vera, I. M. S., Côté, I., Flaveny, C. A., Wanninayake, U. S., Chatterjee, A., Walker, J. K., Steinauer, N., Zhang, J., Coons, L. A., et al. (2023) · Pharmacological Reviews · doi:10.1124/pharmrev.121.000436 · Cited by 54
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“4 It is notable that these treatments are also capable of reducing fat liver content and improving biomarkers of NAFLD.”
BackgroundPeroxisome Proliferator-Activated Receptor Agonists and Bladder Cancer: Lessons from Animal Studies
Tseng, C., & Tseng, F.-H. (2012) · Journal of Environmental Science and Health Part C · doi:10.1080/10590501.2012.735519 · Cited by 49
“It is also worthwhile to point out that the maximum dose of 45 mg is always used in white people [11, 66], but such a dose is rarely used in Asian patients in our daily clinical practice.”
BackgroundSun, W., Sang, Y., Zhang, B., Yu, X., Qin-min, X., Xiu, Z., & Dong, Y. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2016.12.096 · Cited by 49
Should Side Effects Influence the Selection of Antidiabetic Therapies in Type 2 Diabetes?
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Pioglitazone attenuates valvular calcification induced by hypercholesterolemia
Chu, Y., Lund, D. D., Weiss, R. M., Brooks, R. M., Doshi, H., Hajj, G. P., Sigmund, C. D., & Heistad, D. D. (2013) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.112.300794 · Cited by 49
“Activation of PPARγ by thiazolidinedione (TZD) ligands is used commonly for treatment of patients with impaired glucose tolerance and type II diabetes mellitus.(21) To minimize the effect on metabolism, we used a relatively low dose of pioglitazone (Pio) at which no effect on plasma glucose or body weight was observed.”
MethodTripathy, D., Schwenke, D. C., Banerji, M., Bray, G. A., Buchanan, T. A., Clement, S. C., Henry, R. R., Kitabchi, A. E., Mudaliar, S. R. D., Ratner, R. E., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-4202 · Cited by 49
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Biomarkers and immune-modulating therapies for Type 2 diabetes
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Gabriel, R., Boukichou-Abdelkader, N., Acosta, T., Gilis‐Januszewska, A., Gómez‐Huelgas, R., Makrilakis, K., Kamenov, Z. A., Paulweber, B., Satman, İ., Djordjević, P., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0231196 · Cited by 47
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“It is also able to lower the risk of all-cause mortality, myocardial infarction, or cerebrovascular accident in T2DM with macro vascular disease [167,168].”
BackgroundFiorentino, T. V., Suraci, E., Arcidiacono, G. P., Cimellaro, A., Mignogna, C., Presta, I., Andreozzi, F., Hribal, M. L., Perticone, F., Donato, G., et al. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-00348 · Cited by 43
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Treating prediabetes: why and how should we do it?
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Prevention of type 2 diabetes mellitus: is it feasible?
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A Review on Thiazolidinediones and Bladder Cancer in Human Studies
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“Effects of Different Daily Doses The daily dose of pioglitazone may be as high as 45 mg in white populations [3,90], but it is always used at a dose of 15–30 mg in Asian populations [57,60].”
BackgroundWu, Y., Li, P., Zhang, D., & Sun, Y. (2017) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2017.5650 · Cited by 41
Evidence for the Prevention of Type 2 Diabetes Mellitus
Shubrook, J. H., Chen, W., & Lim, A. (2018) · Journal of Osteopathic Medicine · doi:10.7556/jaoa.2018.158 · Cited by 49
Functional loss of pancreatic islets in type 2 diabetes: How can we halt it?
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“through physical exercise, pharmacologically using metformin/glitazones, or by lowering blood glucose through the administration of exogenous insulin [38-40].”
BackgroundRuseva, A., Michalak, W., Zhao, Z., Fabricatore, A., Hartaigh, B. Ó., & Umashanker, D. (2024) · Obesity Science & Practice · doi:10.1002/osp4.737 · Cited by 40
Decreased Insulin Clearance in Individuals with Elevated 1-h Post-Load Plasma Glucose Levels
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“There is compelling evidence that lifestyle changes [1,2] and pharmacological intervention [2–4] may prevent or delay progression from impaired glucose tolerance (IGT) to type 2 diabetes.”
3. Prevention or Delay of Diabetes and Associated Comorbidities: Standards of Care in Diabetes—2026
Bajaj, M. S., McCoy, R. G., Balapattabi, K., Bannuru, R. R., Bellini, N. J., Bennett, A. K., Beverly, E. A., Early, K. B., ChallaSivaKanaka, S., Echouffo-Tcheugui, J. B., et al. (2025) · Diabetes Care · doi:10.2337/dc26-s003 · Cited by 72
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“Peroxisome proliferator-activated receptor-g (PPARg) is a member of the ligand-activated nuclear receptor family with critical functions in energy balance and prominent atheroprotective effects [13,14].”
BackgroundUltra‐Fast Label‐Free Serum Metabolic Diagnosis of Coronary Heart Disease via a Deep Stabilizer
Zhang, M., Huang, L., Yang, J., Xu, W. L., Su, H., Cao, J., Wang, Q., Pu, J., & Qian, K. (2021) · Advanced Science · doi:10.1002/advs.202101333 · Cited by 38
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Tricò, D., Galderisi, A., Mari, A., Santoro, N., & Caprio, S. (2019) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13640 · Cited by 39
Current and Future Treatments in the Fight against Non-Alcoholic Fatty Liver Disease
Smeuninx, B., Boslem, E., & Febbraio, M. A. (2020) · Cancers · doi:10.3390/cancers12071714 · Cited by 39
“However, analysis was not performed in lean individuals [157].”
BackgroundHan, J., Yang, N., Zhang, F., Zhang, C., Liang, F., Xie, W., & Chen, W. (2015) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2015.05.016 · Cited by 39
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Self-citationDoes Weight Gain Associated with Thiazolidinedione Use Negatively Affect Cardiometabolic Health?
Ko, K. D., Kim, K. K., & Lee, K. R. (2017) · Journal of Obesity & Metabolic Syndrome · doi:10.7570/jomes.2017.26.2.102 · Cited by 42
Double-blind, placebo-controlled trial of pioglitazone for bipolar depression.
Aftab, A., Kemp, D. E., Ganocy, S., Schinagle, M., Conroy, C. M., Brownrigg, B., D'Arcangelo, N., Goto, T., Woods, N., Serrano, M. B., et al. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.11.090 · Cited by 41
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The prevention of diabetes and cardiovascular disease in people with schizophrenia
Holt, R. I. G. (2015) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12443 · Cited by 37
“Several pharmacological interventions from two groups, one using drugs that are currently used to treat diabetes, including metformin (21, 22), acarbose (30) and thiazolinediones (31, 32) and the other using drugs for obesity, primarily orlistat (33), have been shown to reduce the incident diabetes (Table 2).”
BackgroundBray, G. A., Smith, S. R., Banerji, M. A., Tripathy, D., Clément, S., Buchanan, T. A., Henry, R. R., Kitabchi, A. E., Mudaliar, S. R. D., Musi, N., et al. (2013) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12099 · Cited by 38
“Men and women ≥18 years of age with IGT [2-h glucose of 140–199 mg/dl during a single oral glucose tolerance test (OGTT)] and body mass index (BMI) >25 kg/m2 were eligible if they had fasting plasma glucose (FPG) of 95–125 mg/dl and at least one of the following five additional risk factor for diabetes: (i) ≥1 compone…”
BackgroundInfluentialSelf-citationXiang, A. H., Trigo, E., Martinez, M., Katkhouda, N., Beale, E., Wang, X., Wu, J., Chow, T., Montgomery, C., Nayak, K. S., et al. (2018) · Diabetes Care · doi:10.2337/dc18-1662 · Cited by 37
Self-citationPostprandial hyperglycemia and endothelial function in type 2 diabetes: focus on mitiglinide
Kitasato, L., Tojo, T., Hatakeyama, Y., Kameda, R., Hashikata, T., & Yamaoka‐Tojo, M. (2012) · Cardiovascular Diabetology · doi:10.1186/1475-2840-11-79 · Cited by 36
“Compared to placebo, pioglitazone reduced the risk of conversion of impaired glucose tolerance to type 2 diabetes by 72%, but it was associated with significant weight gain and edema [68].”
BackgroundAn endocrine perspective of nonalcoholic fatty liver disease (NAFLD)
Lomonaco, R., Chen, J., & Cusi, K. J. (2011) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/2042018811419157 · Cited by 37
“They are insulin-sensitizing agents approved for the treatment of T2DM only, but also effective in halting the progression of prediabetes to diabetes [DeFronzo et al. 2011; The DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators, 2006].”
BackgroundPioglitazone inhibits mitochondrial pyruvate metabolism and glucose production in hepatocytes
Shannon, C. E., Daniele, G., Galindo, C., Abdul-Ghani, M. A., DeFronzo, R. A., & Norton, L. (2016) · FEBS Journal · doi:10.1111/febs.13992 · Cited by 36
Self-citationThe Management of Type 2 Diabetic Patients with Hypoglycaemic Agents
Tsang, M.-W. (2012) · ISRN Endocrinology · doi:10.5402/2012/478120 · Cited by 36
“Studies with thiazolidinediones in prediabetes, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), had demonstrated significant reduction in progression from IGT to T2DM by 62–72% [22–24].”
BackgroundAvilés-Santa, L. M., Colón‐Ramos, U., Lindberg, N. M., Mattei, J., Pasquel, F. J., & Pérez, C. M. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00298 · Cited by 38
“0001) among NHWs, AAs and Hispanics/Latinos compared to placebo (394).”
BackgroundLim, S. K., Sakuma, I., Quon, M. J., & Koh, K. K. (2012) · International Journal of Cardiology · doi:10.1016/j.ijcard.2012.10.037 · Cited by 36
“Indeed, when testing effects of pioglitazone in patients early in the course of metabolic disease when pathophysiology is reversible, pioglitazone had a beneficial risk-benefit profile with respect to both metabolic and cardiovascular outcomes [40].”
BackgroundArmato, J., DeFronzo, R. A., Abdul-Ghani, M., & Ruby, R. (2012) · Endocrine Practice · doi:10.4158/ep11194.or · Cited by 35
Self-citationOral Antidiabetic Drugs and Regression from Prediabetes to Normoglycemia: A Meta-Analysis
Phung, O. J., Baker, W. L., Tongbram, V., Bhardwaj, A., & Coleman, C. I. (2012) · Annals of Pharmacotherapy · doi:10.1345/aph.1q554 · Cited by 35
DeFronzo, R. A., Mehta, R. J., & Schnure, J. J. (2013) · Hospital Practice · doi:10.3810/hp.2013.04.1062 · Cited by 35
Self-citationJinlida for Diabetes Prevention in Impaired Glucose Tolerance and Multiple Metabolic Abnormalities
Ji, H., Zhao, X., Chen, X., Fang, H., Gao, H., Wei, G., Zhang, M., Kuang, H., Yang, B., Cai, X., et al. (2024) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2024.1190 · Cited by 37
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Sesti, G., Fiorentino, T. V., Succurro, E., Perticone, M., Arturi, F., Sciacqua, A., & Perticone, F. (2014) · Acta Diabetologica · doi:10.1007/s00592-013-0539-x · Cited by 34
Mehtälä, J., Khanfir, H., Bennett, D., Ye, Y., Korhonen, P. A., & Hoti, F. J. (2018) · Diabetology International · doi:10.1007/s13340-018-0360-4 · Cited by 36
“The Actos Now for Prevention of Diabetes (ACT NOW) clinical trial showed that pioglitazone reduced the risk of T2DM conversion in adults with impaired glucose tolerance by 72% [4, 5].”
BackgroundQin, N., Zhou, Z., Zhao, W., Zou, K., Shi, W., Yu, C., Liu, X., Dong, Z.-H., Mao, Y., Liu, X., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.637781 · Cited by 33
“Therefore, we speculate that IVF-FET conceived male mice are predisposed to T2D.”
BackgroundInfluentialGroner, J., Göpferich, A. M., & Breunig, M. (2021) · Journal of Controlled Release · doi:10.1016/j.jconrel.2021.03.034 · Cited by 34
The Disposition Index Does Not Reflect β-Cell Function in IGT Subjects Treated With Pioglitazone
DeFronzo, R. A., Tripathy, D., Abdul‐Ghani, M. A., Musi, N., & Gastaldelli, A. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1515 · Cited by 36
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Detecting people at high risk of type 2 diabetes- How do we find them and who should be treated?
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Prevention of type 2 Diabetes Mellitus: Potential of pharmacological agents
Samson, S. L., & Garber, A. J. (2016) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2016.06.005 · Cited by 37
“[35] reported the results of the AC T NOW study, in which 602 patients with IGT were randomized to placebo or 45 mg daily of pioglitazone for a median of 2.”
ResultEthnic Similarities and Differences in the Relationship between Beta Cell Mass and Diabetes
Inaishi, J., & Saisho, Y. (2017) · Journal of Clinical Medicine · doi:10.3390/jcm6120113 · Cited by 33
“Several clinical trials have shown that lifestyle modification and insulin sensitizers that decrease beta cell workload [39,40], but not insulin secretagogues [41], are effective at preventing the development of T2DM.”
BackgroundDalcetrapib Reduces Risk of New-Onset Diabetes in Patients With Coronary Heart Disease
Schwartz, G. G., Leiter, L. A., Ballantyne, C. M., Barter, P. J., Black, D. M., Kallend, D. G., Laghrissi‐Thode, F., Leitersdorf, E., McMurray, J. J. V., Nicholls, S. J., et al. (2020) · Diabetes Care · doi:10.2337/dc19-2204 · Cited by 34
“Implications In the present analysis, the observed effect size of dalcetrapib treatment on incident diabetes was smaller than that previously seen with thiazolidinediones and comparable to that observed with metformin (27, 28).”
Thiazolidinedione Response in Familial Lipodystrophy Patients with LMNA Mutations: A Case Series
Luedtke, A., Boschmann, M., Colpe, C., Engeli, S., Adams, F., Birkenfeld, A. L., Haufe, S., Rahn, G., Luft, F. C., Schmidt, H., et al. (2012) · Hormone and Metabolic Research · doi:10.1055/s-0031-1301284 · Cited by 33
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Uncoupling proteins as a therapeutic target to protect the diabetic heart
Dludla, P. V., Nkambule, B. B., Tiano, L., Louw, J., Jastroch, M., & Mazibuko-Mbeje, S. E. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.09.013 · Cited by 32
Non alcoholic fatty liver disease and risk of incident diabetes in subjects who are not obese
Sung, K.-C., Seo, D.-C., Lee, S., Lee, M.-Y., Wild, S. H., & Byrne, C. D. (2019) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2019.01.016 · Cited by 32
“Whereas both metformin [25] and pioglitazone [26] have been shown to decrease risk of type 2 diabetes,”
BackgroundGuardado‐Mendoza, R., Salazar-López, S. S., Alvarez-Canales, M. F. D. L. L., Farfán-Vázquez, D., Martínez-López, Y. E., Jiménez-Ceja, L. M., Suárez-Pérez, E. L., Angulo-Romero, F., Evia-Viscarra, M. L., de Oca-Loyola, M. L. M., et al. (2019) · Metabolism · doi:10.1016/j.metabol.2019.154054 · Cited by 33
Pioglitazone reduces epicardial fat and improves diastolic function in patients with type 2 diabetes
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“However, evidence has since emerged demonstrating that disruption of adipocyte differentiation and/or expansion is maladaptive and leads to ectopic fat accumulation and metabolic dysfunction, including insulin resistance and T2DM [4,5].”
BackgroundInfluentialHamilton, B. S., Himmelsbach, F., Nar, H., Schuler‐Metz, A., Krosky, P. M., Guo, J., Guo, R., Meng, S., Zhao, Y., Lala, D. S., et al. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.10.053 · Cited by 30
“In addition to side effects that can limit usage, most of these agents have not yet demonstrated positive effects upon cardiovascular outcomes, and have also not demonstrated lasting durability (Lamanna et al., 2011; Bacha et al., 2012; Defronzo et al., 2011).”
BackgroundPrediabetes: To treat or not to treat?
Moutzouri, E., Tsimihodimos, V., Rizos, E. C., & Elisaf, M. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2011.10.007 · Cited by 31
Does Elevated Plasma Triglyceride Level Independently Predict Impaired Fasting Glucose?
Lin, S. X., Berlin, I., Younge, R. G., Jin, Z., Sibley, C. T., Schreiner, P. J., Szklo, M., & Bertoni, A. G. (2012) · Diabetes Care · doi:10.2337/dc12-0355 · Cited by 32
Aguilar, R. B. (2011) · Clinical Therapeutics · doi:10.1016/j.clinthera.2011.04.008 · Cited by 31
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“The inclusion/exclusion criteria and subject characteristics have been published (7, 21).”
BackgroundSelf-citationAndreozzi, F., Mannino, G. C., Perticone, M., Perticone, F., & Sesti, G. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.11.020 · Cited by 30
Fiorentino, T. V., Succurro, E., Andreozzi, F., et al. (2018) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3096 · Cited by 29
“7% and 1‐hour post‐load plasma glucose <155 mg/dL; (2) 257 subjects had HbA1c < 5.”
BackgroundCOSMIC project: consensus on the objectives of the metabolic syndrome in clinic
Pedro‐Botet, J., Ascaso, J. F., Barrios, V., de la Sierra, A., Escalada, J., Millán, J., Mostaza, J. M., Pérez‐Martínez, P., Pintó, X., Salas‐Salvadó, J., et al. (2018) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s165740 · Cited by 31
“In patients with prediabetes (MetS), metformin has been shown to assist in the prevention of diabetes by 25%–30%(30) and pioglitazone by 72%.(34) Conversely, pioglitazone has also been shown to be effective in diabetes prevention in patients with fatty liver and for the control of fatty acid supply to the liver.”
BackgroundReframing prediabetes: A call for better risk stratification and intervention
Kim, S. H. (2024) · Journal of Internal Medicine · doi:10.1111/joim.13786 · Cited by 31
“Several antihyper-glycemic [38, 71–73] and weight-loss medications [74, 75] have been shown to reduce the incidence of T2DM in individuals with prediabetes.”
BackgroundIncretin Therapy – Present and Future
Garber, A. J. (2011) · The Review of Diabetic Studies · doi:10.1900/rds.2011.8.307 · Cited by 29
“001) and increased incidence of edema compared with placebo [87, 88].”
BackgroundPPARγ in head and neck cancer prevention
Burotto, M., & Szabo, E. M. (2014) · Oral Oncology · doi:10.1016/j.oraloncology.2013.12.020 · Cited by 30
“On the other hand, use of pioglitazone in the metabolic syndrome has been associated with decreased progression to overt diabetes [51].”
BackgroundRasouli, N., Kern, P. A., Elbein, S. C., Sharma, N., & Das, S. K. (2012) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e328352a72e · Cited by 27
Metadata
- Authors
- DeFronzo, R. A., Tripathy, D., Schwenke, D. C., Banerji, M., Bray, G. A., Buchanan, T. A., Clement, S. C., Henry, R. R., Hodis, H. N., Kitabchi, A. E., Mack, W. J., Mudaliar, S., Ratner, R. E., Williams, K., Stentz, F. B., Musi, N., & Reaven, P. D.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Texas Diabetes Institute (US)
- Phoenix VA Health Care System (US)
- Pennington Biomedical Research Center (US)
- University of Southern California (US)
- Georgetown University (US)
- University of California San Diego (US)
- University of Tennessee Health Science Center (US)
- MedStar Health Research Institute (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2011-03-24
- Volume
- 364
- Issue
- 12
- Pages
- 1104-1115
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2131330057
- Semantic Scholar
- 2537f2b5521882869eda52ee137db9e85431749f
- Cited by
- 766
- References
- 42
- Citations by year
- 2026: 26 · 2025: 20 · 2024: 44 · 2023: 35 · 2022: 35 · 2021: 49 · 2020: 45 · 2019: 45 · 2018: 58 · 2017: 54 · 2016: 53 · 2015: 61 · 2014: 61 · 2013: 69 · 2012: 69
- FWCI
- 49.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Research Resources (M01-RR00221, M01RR000043)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- pioglitazone, impaired glucose tolerance, type 2 diabetes prevention, thiazolidinediones, glucose tolerance, fasting blood glucose, HbA1c, carotid intima-media thickening, diastolic blood pressure, HDL cholesterol, cardiovascular risk, PPARγ agonists, statins, fibrates, nicotinic acid, fenofibrate
- MeSH terms
- Pioglitazone, Adolescent, Adult, Blood Glucose, Blood Pressure, Diabetes Mellitus, Type 2, Double-Blind Method, Edema, Follow-Up Studies, Glucose Tolerance Test, Humans, Hypoglycemic Agents, Insulin Resistance, Middle Aged, Weight Gain, Life Tables, Proportional Hazards Models, Glucose Intolerance, Thiazolidinediones, Kaplan-Meier Estimate, Young Adult
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